Abstract 153: Born with a Single Kidney versus Nephrectomy: Similar End Point, Different Mechanism of Injury

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Xuexiang Wang ◽  
Ashley Johnson ◽  
Jonathan Lee ◽  
Leah Solberg-Woods ◽  
Michael R Garrett
Keyword(s):  
Renal Function ◽  
Renal Injury ◽  
Time Course ◽  
Course Evaluation ◽  
Pathophysiological Mechanism ◽  
Mechanism Of Injury ◽  
Nephron Number ◽  
Unilateral Renal Agenesis ◽  
Renal Ablation ◽  
Single Kidney

A relatively common abnormality of the urogenital tract in humans is the development of only a single kidney (1:500 to 1:1000). Clinical studies suggest that patients born with a single kidney can develop proteinuria, hypertension, and even renal failure later in life. In contrast, studies in children who undergo nephrectomy or adults who serve as kidney donors appear to exhibit little difference in renal function compared to two-kidney subjects. Invasive techniques such as nephrectomy or renal ablation have been used to generate animal models to recapitulate this human congenital disorder. The progression of injury in these models is attributed to hyperfiltration which refers to changes in hemodynamics that cause glomerular damage leading to hypertension. Recently, our lab developed a new genetic animal model [heterogeneous stock derived model of unilateral renal agenesis, (HSRA)] that develops with a single kidney in 50-75% of offspring. The model is characterized by reduced nephron number, kidney hypertrophy, and renal injury that leads to a decline in renal function. Time course evaluation of blood pressure, renal hemodynamics, and renal injury was performed in 4 groups; (1) HSRA-S (1-kidney), (2) HSRA-C (2-kidney littermates), (3) HSRA-UNX3 (uninephrectomy-week 3) and (4) HSRA-UNX8 (uninephrectomy-week 8). Nephrectomized animals demonstrated hyperfiltration, whereas single kidney animals (HSRA-S) did not. This suggests a different pathophysiological mechanism of injury between congenital and nephrectomized rats. At later time points, proteinuria for HSRA-UNX3 (82±22.9 mg/24h) and HSRA-UNX8 (46±18.1) were significantly higher than HSRA-C (11±6.4), while HSRA-S (109±15.7) demonstrated the highest proteinuria. GFR was lowest in HSRA-S (656±123.9 ul/min/gKW), followed by HSRA-UNX3 (1151±112.4), HSRA-UNX8 (1309±98.3) and HSRA-C (1544±111.7). Microarray studies have identified several developmental genes ( Hox5b , Smoc2 and c- Kit ) that may be linked to reduced nephron number and other structural changes that could predispose the HSRA-S to kidney injury later in life. These results demonstrate that rats born with a single kidney are more prone to renal injury than nephrectomized rats and the mechanism is likely different.

scholarly journals Spontaneous one-kidney rats are more susceptible to develop hypertension by DOCA-NaCl and subsequent kidney injury compared with uninephrectomized rats

2016 ◽  
Vol 310 (10) ◽  
pp. F1054-F1064 ◽  
Author(s):  
Xuexiang Wang ◽  
Ashley C. Johnson ◽  
Jennifer M. Sasser ◽  
Jan M. Williams ◽  
Leah C. Solberg Woods ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Function ◽  
Time Course ◽  
Kidney Injury ◽  
Solitary Kidney ◽  
Course Evaluation ◽  
Significant Rise ◽  
Kidney Weight ◽  
Unilateral Renal Agenesis ◽  
Single Kidney

There is little clinical data of how hypertension may influence individuals with nephron deficiency in the context of being born with a single kidney. We recently developed a new rat model (the heterogeneous stock-derived model of unilateral renal agenesis rat) that is born with a single kidney and exhibits progressive kidney injury and decline in kidney function with age. We hypothesized that DOCA-salt would induce a greater increase in blood pressure and therefore accelerate the progression of kidney injury in rats born with a solitary kidney compared with rats that have undergone unilateral nephrectomy. Time course evaluation of blood pressure, kidney injury, and renal hemodynamics was performed in the following six groups of animals from weeks 13 to 18: 1) DOCA-treated rats with a solitary kidney (DOCA+S group), 2) placebo-treated rats with a solitary kidney, 3) DOCA-treated control rats with two kidneys (DOCA+C group), 4) placebo-treated control rats with two kidneys, 5) DOCA-treated rats with two kidneys that underwent uninephrectomy (DOCA+UNX8 group), and 6) placebo-treated rats with two kidneys that underwent uninephrectomy. DOCA+S rats demonstrated a significant rise ( P < 0.05) in blood pressure (192 ± 4 mmHg), proteinuria (205 ± 31 mg/24 h), and a decline in glomerular filtration rate (600 ± 42 μl·min−1·g kidney weight−1) relative to the DOCA+UNX8 (173 ± 3 mmHg, 76 ± 26 mg/24 h, and 963 ± 36 μl·min−1·g kidney weight−1) and DOCA+C (154 ± 2 mmHg, 7 ± 1 mg/24 h, and 1,484 ± 121 μl·min−1·g kidney weight−1) groups. Placebo-treated groups showed no significant change among the three groups. An assessment of renal injury markers via real-time PCR/Western blot analysis and histological analysis was concordant with the measured physiological parameters. In summary, congenital solitary kidney rats are highly susceptible to the induction of hypertension compared with uninephrectomized rats, suggesting that low nephron endowment is an important driver of elevated blood pressure, hastening nephron injury through the transmission of elevated systemic blood pressure and thereby accelerating decline in kidney function.

scholarly journals Heterogeneous stock rats: a new model to study the genetics of renal phenotypes

2010 ◽  
Vol 298 (6) ◽  
pp. F1484-F1491 ◽  
Author(s):  
Leah C. Solberg Woods ◽  
Cary Stelloh ◽  
Kevin R. Regner ◽  
Tiffany Schwabe ◽  
Jessica Eisenhauer ◽  
...  
Keyword(s):  
Complex Traits ◽  
Time Course ◽  
Kidney Injury ◽  
Large Degree ◽  
The United States ◽  
Significant Degree ◽  
Course Evaluation ◽  
Tubulointerstitial Injury ◽  
Unilateral Renal Agenesis ◽  
Heterogeneous Stock

Chronic kidney disease is a growing medical concern, with an estimated 25.6 million people in the United States exhibiting some degree of kidney injury and/or decline in kidney function. Animal models provide great insight into the study of the genetics of complex diseases. In particular, heterogeneous stock (HS) rats represent a unique genetic resource enabling rapid fine-mapping of complex traits. However, they have not been explored as a model to study renal phenotypes. To evaluate the usefulness of HS rats in the genetics of renal traits, a time course evaluation ( weeks 8–40) was performed for several renal phenotypes. As expected, a large degree of variation was seen for most renal traits. By week 24, three (of 40) rats exhibited marked proteinuria that increased gradually until week 40 and ranged from 33.7 to 80.2 mg/24 h. Detailed histological analysis confirmed renal damage in these rats. In addition, several rats consistently exhibited significant hematuria (5/41). Interestingly, these rats were not the same rats that exhibited proteinuria, indicating that susceptibility to different types of kidney injury is likely segregating within the HS population. One HS rat exhibited unilateral renal agenesis (URA), which was accompanied by a significant degree of proteinuria and glomerular and tubulointerstitial injury. The parents of this HS rat were identified and bred further. Additional offspring of this pair were observed to exhibit URA at frequency between 40% and 60%. In summary, these novel data demonstrate that HS rats exhibit variation in proteinuria and other kidney-related traits, confirming that the model harbors susceptibility alleles for kidney injury and providing the basis for further genetic studies.

scholarly journals Time-course evaluation of blood glucose changes in response to insulin delivery in critically ill patients

Critical Care ◽  
2014 ◽  
Vol 18 (Suppl 1) ◽  
pp. P440
Author(s):  
F Bass ◽  
S Bird ◽  
N Hammond ◽  
J Myburgh ◽  
S Finfer
Keyword(s):  
Blood Glucose ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Time Course ◽  
Insulin Delivery ◽  
Course Evaluation

scholarly journals Comparative Proteomics Analysis of Mouse Habu Nephritis Models with and without Unilateral Nephrectomy

2016 ◽  
Vol 39 (5) ◽  
pp. 1761-1776 ◽  
Author(s):  
Lei Chen ◽  
Yang Lu ◽  
Jun Wen ◽  
Xu Wang ◽  
Lingling Wu ◽  
...  
Keyword(s):  
Renal Injury ◽  
Quantitative Proteomics ◽  
Mesangial Cells ◽  
Unilateral Nephrectomy ◽  
Label Free ◽  
Proteomics Analysis ◽  
Single Kidney ◽  
Regulation Of Actin Cytoskeleton ◽  
Insight Into

Background/Aims: Individuals possessing a single kidney are at greater risk of renal injury upon exposure to harmful stimuli. This study aimed to explore the pathogenesis of renal injury in glomerulonephritis with versus without unilateral nephrectomy (UNX). Methods: Histological analysis and label-free quantitative proteomics were performed on two models—the Habu snake venom-induced glomerulonephritis model with versus without UNX (HabuU and Habu models, respectively). The role of villin 1, a differentially expressed protein (DEP) in mouse mesangial cells, was investigated. Results: Persistent mesangiolysis and focal hypercellularity together with reduced activation of cell proliferation in the HabuU model induced more serious renal injury compared with that in the Habu model. The DEPs between the two models were identified by label-free liquid chromatography-mass spectrometry. The KEGG pathway results indicated that regulation of actin cytoskeleton and focal adhesion were specifically enriched in the HabuU model. The cytoskeleton regulation protein villin 1 was downregulated in the HabuU model, but unchanged in the Habu model. Knockdown of villin 1 promoted apoptosis and inhibited the proliferation of mouse mesangial cells, suggesting villin 1 to be involved in qlomerular lesion self-repair insufficiency. Conclusion: By assessing the proteomic profiles of the two models, this study identified several important differences, particularly villin 1 expression, in regulatory mechanisms between the two models. Our findings provide novel insight into the mechanism of serious renal injury in glomerulonephritis with UNX.

scholarly journals Time-course evaluation of intestinal structural disorders in a porcine model of intra-abdominal hypertension by mechanical intestinal obstruction

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191420 ◽  
Author(s):  
Ester Párraga Ros ◽  
Laura Correa-Martín ◽  
Francisco M. Sánchez-Margallo ◽  
Irma Eugenia Candanosa-Aranda ◽  
Manu L. N. G. Malbrain ◽  
...  
Keyword(s):  
Intestinal Obstruction ◽  
Time Course ◽  
Porcine Model ◽  
Course Evaluation ◽  
Mechanical Intestinal Obstruction ◽  
Structural Disorders ◽  
Abdominal Hypertension

AT1 blockade during lactation as a model of chronic nephropathy: mechanisms of renal injury

2008 ◽  
Vol 294 (6) ◽  
pp. F1345-F1353 ◽  
Author(s):  
Flavia Gomes Machado ◽  
Elizabete Pereira Barros Poppi ◽  
Camilla Fanelli ◽  
Denise Maria Avancini Costa Malheiros ◽  
Roberto Zatz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Injury ◽  
Time Course ◽  
Structural Changes ◽  
Adult Life ◽  
Renin Angiotensin System ◽  
Urine Osmolality ◽  
Systemic Hypertension ◽  
Advanced Stages

Suppression of the renin-angiotensin system during lactation causes irreversible renal structural changes. In this study we investigated 1) the time course and the mechanisms underlying the chronic kidney disease caused by administration of the AT1 receptor blocker losartan during lactation, and 2) whether this untoward effect can be used to engender a new model of chronic kidney disease. Male Munich-Wistar pups were divided into two groups: C, whose mothers were untreated, and LLact, whose mothers received oral losartan (250 mg·kg−1·day−1) during the first 20 days after delivery. At 3 mo of life, both nephron number and the glomerular filtration rate were reduced in LLact rats, whereas glomerular pressure was elevated. Unselective proteinuria and decreased expression of the zonula occludens-1 protein were also observed, along with modest glomerulosclerosis, significant interstitial expansion and inflammation, and wide glomerular volume variation, with a stable subpopulation of exceedingly small glomeruli. In addition, the urine osmolality was persistently lower in LLact rats. At 10 mo of age, LLact rats exhibited systemic hypertension, heavy albuminuria, substantial glomerulosclerosis, severe renal interstitial expansion and inflammation, and creatinine retention. Conclusions are that 1) oral losartan during lactation can be used as a simple and easily reproducible model of chronic kidney disease in adult life, associated with low mortality and no arterial hypertension until advanced stages; and 2) the mechanisms involved in the progression of renal injury in this model include glomerular hypertension, glomerular hypertrophy, podocyte injury, and interstitial inflammation.

Renal Impairment in Patients With Multiple Myeloma: A Consensus Statement on Behalf of the International Myeloma Working Group

2010 ◽  
Vol 28 (33) ◽  
pp. 4976-4984 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Evangelos Terpos ◽  
Asher Chanan-Khan ◽  
Nelson Leung ◽  
Heinz Ludwig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Impairment ◽  
Light Chain ◽  
Renal Injury ◽  
High Dose ◽  
Acute Renal Injury ◽  
High Dose Dexamethasone ◽  
Cast Nephropathy ◽  
High Dose Melphalan

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

Insights into Dahl salt-sensitive hypertension revealed by temporal patterns of renal medullary gene expression

2003 ◽  
Vol 12 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Mingyu Liang ◽  
Baozhi Yuan ◽  
Elizabeth Rute ◽  
Andrew S. Greene ◽  
Michael Olivier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Injury ◽  
Time Course ◽  
Expression Patterns ◽  
Renal Medulla ◽  
Temporal Patterns ◽  
Reference Distribution ◽  
Arterial Blood ◽  
Renal Tubular ◽  
Salt Sensitive Hypertension

Dahl salt-sensitive SS and consomic, salt-resistant SS-13BN/Mcw rats possess a highly similar genetic background but exhibit substantial differences in blood pressure salt sensitivity. We used cDNA microarrays to examine sequential changes of mRNA expression of ∼2,000 currently known rat genes in the renal medulla (a tissue critical for long-term blood pressure regulation) in SS and SS-13BN/Mcw rats in response to a high-salt diet (16 h, 3 days, or 2 wk). Differentially expressed genes in each between-group comparison were identified based on a threshold determined experimentally using a reference distribution that was constructed by comparing rats within the same group. A difference analysis of 54 microarrays identified 50 genes that exhibited the most distinct temporal patterns of expression between SS and SS-13BN/Mcw rats over the entire time course. Thirty of these genes could be linked to the regulation of arterial blood pressure or renal injury based on their known involvement in functional pathways such as renal tubular transport, metabolism of vasoactive substances, extracellular matrix formation, and apoptosis. Importantly, the majority of the 30 genes exhibited temporal expression patterns that would be expected to lower arterial pressure and reduce renal injury in SS-13BN/Mcw compared with SS rats. The phenotypic impact of the other 20 genes was less clear. These 50 genes are widely distributed on chromosome 13 and several other chromosomes. This suggested that primary genetic defects, although important, are unlikely to be solely responsible for the full manifestation of this type of hypertension and associated injury phenotypes. In summary, the results of this study identified a number of pathways potentially important for the amelioration of hypertension and renal injury in SS-13BN/Mcw rats, and these results generated a series of testable hypotheses related to the role of the renal medulla in the complex mechanism of salt-sensitive hypertension.

Time-Course for Recovery of Renal Function After Unilateral (Single-Tract) Percutaneous Access in the Pig

2010 ◽  
Vol 24 (2) ◽  
pp. 283-288 ◽  
Author(s):  
Rajash K. Handa ◽  
Lynn R. Willis ◽  
Bret A. Connors ◽  
Sujuan Gao ◽  
Andrew P. Evan ◽  
...  
Keyword(s):  
Renal Function ◽  
Time Course ◽  
Percutaneous Access

scholarly journals Acute-on-Chronic Kidney Injury in Thyroid Hormone Withdrawal: A Case with Possible Implications for Radioactive Iodine Planning

2015 ◽  
Vol 2015 ◽  
pp. 1-3 ◽  
Author(s):  
Elizabeth A. McAninch ◽  
Violet S. Lagari
Keyword(s):  
Renal Function ◽  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Renal Insufficiency ◽  
Radioactive Iodine ◽  
Kidney Injury ◽  
Unilateral Renal Agenesis ◽  
Thyroid Hormone Withdrawal ◽  
Ckd Stage ◽  
Acute Hypothyroidism

The association between renal dysfunction and hypothyroidism is of increasing clinical importance as thyroid hormone replacement may attenuate decline in renal function and improve cardiovascular outcomes in patients with chronic kidney disease (CKD). Although multiple mechanisms for the induction of renal insufficiency in hypothyroidism have been described, the renal impact of short-term, acute hypothyroidism is unknown, which has possible implications for thyroid cancer patients preparing to receive radioactive iodine (RAI). A 56-year-old gentleman with history of unilateral renal agenesis and CKD stage III presented with intermediate-risk papillary thyroid cancer. In preparation for RAI, he underwent thyroid hormone withdrawal (THW) associated with acute kidney injury (AKI), as marked by a decrease in his estimated GFR from 53 to 32 mL/min/1.73 m2. Upon resumption of thyroid hormone, renal function returned to baseline within months. Although AKI in this case was not otherwise associated with adverse outcome and reversed upon resumption of thyroid hormone, it is possible that this phenomenon could result in potential harm, particularly in the patient with baseline renal insufficiency. In CKD patients, preparation for RAI therapy may require special consideration; future studies should address the role of recombinant TSH to mitigate deleterious renal effects of acute hypothyroidism in this setting.

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