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.

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 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.

Abstract 161: Identification of Genetic Variants Associated with Kidney Injury That Leads to Increased Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ashlyn C Harmon ◽  
Ashley C Johnson ◽  
Santosh Atanur ◽  
Klio Maratou ◽  
Tim Aitman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Bone Marrow ◽  
Immune Response ◽  
Renal Function ◽  
Kidney Disease ◽  
Kidney Function ◽  
Genetic Variants ◽  
Kidney Injury ◽  
Chromosome 11 ◽  
Genomic Locus

Hypertension, diabetes and obesity, along with genetic predisposition, contribute to the growing number of chronic kidney disease patients. Our novel congenic model [S.SHR(11)] was developed through genetic modification of the Dahl salt-sensitive (S) rat, a model of hypertension related renal disease. The S.SHR(11) strain exhibits accelerated kidney injury compared to the already highly susceptible S rat. On either a low or high-salt diet, the S.SHR(11) model predominately exhibited more tubulointerstitial fibrosis compared to the S rat (17.1±1.29% vs. 12.9±1.22%). Increased α-SMA and macrophage infiltration was also observed. The S and S.SHR(11) had similar blood pressure (week 12), despite an early reduction in renal function in the S.SHR(11); however at an advanced age the S.SHR(11) demonstrated significantly higher blood pressure than the S (215±6.6 mm Hg vs. 183±5.9, respectively). This suggests that increased kidney injury is driving the development of hypertension later in life. Since these two animal models are identical with exception of chromosome 11, the causative genetic variants contributing to decreased renal function must reside within this region. The Dahl S and SHR genomes have been sequenced; this data provides a catalog of all the genetic variants between the two models. The 95% confidence interval of the genomic locus contains 28 non-synonymous SNP, with 15 of these SNP occurring within only three genes: Retnlg , Trat1 and Myh15. Two of these genes, Retnlg and Trat1, are known to play a role in immune response leading to our hypothesis that genetic variants in these genes alter protein function and lead to an increased immune response. Bone marrow transplant studies have been initiated to test our hypothesis and preliminary data shows that S rats who receive S.SHR(11) bone marrow have kidney function measurements similar to the S.SHR(11). The sequencing information has also lead to the development of nine new, more refined congenic strains. Through functional analysis of these new congenic animals, identification of the causative genetic variations will be expedited. In summary, we are employing a model of accelerated kidney disease to identify genes or genetic variants responsible for reduced kidney function and hypertension.

COVID-19 in Single Kidney Patient

2022 ◽  
Author(s):  
Rahim Raofi ◽  
Yasaman Pourfarid ◽  
Navid Kalani ◽  
Mohsen Hojat
Keyword(s):  
At Risk ◽  
Renal Agenesis ◽  
Solitary Kidney ◽  
Care Plan ◽  
Unilateral Renal Agenesis ◽  
Area Of Interest ◽  
Unique Approach ◽  
Infectious Disease Specialists ◽  
Renal Patient ◽  
Single Kidney

The COVID-19 pandemic has affected all people in the world, especially those at risk of kidney disorders. Early kidney damage in patients born with unilateral renal agenesis (URA) or solitary kidney can happen. These patients are at risk of chronic kidney disease (CKD), high blood pressure, and developing proteinuria. Unilateral renal agenesis is a cause of CKD. Therefore, it is very interesting that observe a unilateral renal Patient that Suffers from COVID-19. Hence, the management of these patients with COVID‐19 is an area of interest, and a unique approach is warranted. A 43-year-old male patient with unilateral renal presented to our hospital for corona disease. The case was discussed between the nephrologists, Infectious disease specialists, and nursing head nurses for a care plan daily. The patient had unilateral renal disease, and COVID-19 could have a detrimental effect on the renal, but renal tests were normal, and the patient recovered without acute renal complications. The treatment of such patients is the need for teamwork contain nephrologists, critical care nurses, and specialists in infectious and tropical diseases. This was a new experience in Iran.

scholarly journals Sepsis-induced acute kidney injury: kidney protection effects by antioxidants

2018 ◽  
Vol 71 (4) ◽  
pp. 1921-1927 ◽  
Author(s):  
Carolina Ferreira Vasco ◽  
Mirian Watanabe ◽  
Cassiane Dezoti da Fonseca ◽  
Maria de Fátima Fernandes Vattimo
Keyword(s):  
Blood Pressure ◽  
Acute Kidney Injury ◽  
Creatinine Clearance ◽  
Experimental Model ◽  
Kidney Function ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Cecal Ligation And Puncture ◽  
Antioxidant Action ◽  
Average Blood Pressure

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

MO389PREDICTORS OF COMMUNITY-ACQUIRED ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE CARDIAC DISEASES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marina Efremovtseva ◽  
Svetlana Avdoshina ◽  
Maria Markova ◽  
Zhanna Kobalava
Keyword(s):  
Blood Pressure ◽  
Risk Assessment ◽  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Hospital Mortality ◽  
Kidney Function ◽  
Kidney Injury ◽  
Assessment Scale ◽  
Cardiac Diseases ◽  
L 14

Abstract Background and Aims Acute kidney injury (AKI) is a common and serious problem associated with poor prognosis. The aim of the study was to reveal the prevalence and predictors of community-acquired AKI in patients with acute cardiac diseases. Method 566 patients (278 with acute decompensated heart failure (ADHF), 288 with non-ST-elevation acute coronary syndrome (NSTE-ACS), 46% male, 71±11 years (M±SD), smokers 26%, arterial hypertension 91%, previous myocardial infarction (MI) 45%, diabetes mellitus (DM) 28%, atrial fibrillation 35%, chronic kidney disease (CKD) 46%, previous hospitalization with ADHF 36%, ejection fraction (EF) &lt;35% 15%, blood pressure (BP) 142±30/83±16 mmHg) were examined. AKI was diagnosed according 2012 KDIGO Guidelines. Community-acquired AKI was identified in patients with elevated serum creatinine levels on admission, which decreased during hospitalization. Results: Incidence of AKI in all patients, patients with ADHF and NSTE-ACS was 40, 43.5 and 37.2%. In-hospital mortality in patients with AKI was higher than in those with stable kidney function (14.9 vs 3.6%, p&lt;0.001). Community-acquired AKI was present in 18% of patients (20.5 and 15.6% in ADHF and NSTE-ACS respectively), in-hospital mortality was 16.7% (10.5 and 24.4% respectively). The risk assessment scale for community-acquired AKI was developed based on independent predictors of AKI, using binary logistic regression and ROC analysis (AUC 0.860, 95% CI 0.821-0.898). Independent variables included in the model, and the corresponding points (pts) are listed below: clinical and demographic characteristics (male gender - 6 pts, alcohol abuse - 7 pts, DM - 1 pt), present on admission (MI - 5 pts, AHF/ADHF - 9 pts, systolic BP &lt;120 - 10 pts, &lt;110 - 15 pts, &lt;90 mmHg - 27 pts; state of kidney function on admission: serum creatinine &gt;98 and &gt;128 mkmol/L - 14 and 22 pts, GFRCKD-EPI &lt;45 and &lt;15 ml/min/1.73 m2 - 7 and 14 pts; glucose level &gt;7 mmol/L - 4 pts), outpatient intake of ACE inhibitors - 4 pts, absence of spironolactone in outpatient therapy - 1 pt. Diagnostically significant risk score for predicting AKI was &gt;30 pts, the risk prediction model showed sensitivity 89%, specificity 66%. Conclusion Community-acquired AKI is common in patients in acute cardiovascular events, is associated with high mortality, and often is underdiagnosed. Usage of risk assessment scale in clinical practice may help to detect patients with high-risk of AKI on admission. Baseline kidney function and blood pressure level are main predictors of AKI in patients admitted with acute cardiac diseases.

scholarly journals Clinician perspectives on inpatient cystatin C utilization: A qualitative case study at Mayo Clinic

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243618
Author(s):  
James Roland Markos ◽  
Karen S. Schaepe ◽  
Hilary R. Teaford ◽  
Andrew D. Rule ◽  
Kianoush B. Kashani ◽  
...  
Keyword(s):  
Kidney Function ◽  
Cystatin C ◽  
Inpatient Care ◽  
Kidney Injury ◽  
Phenomenological Approach ◽  
Significant Rise ◽  
Added Value ◽  
Multidisciplinary Teams ◽  
Structured Interviews ◽  
Consulting Services

Introduction Serum creatinine (SCr) testing has been the mainstay of kidney function assessment for decades despite known limitations. Cystatin C (CysC) is an alternative biomarker that is generally less affected than SCr by pertinent non-renal factors in hospitalized patients, such as muscle mass. Despite its potential advantages, the adoption of CysC for inpatient care is not widespread. At one hospital with CysC testing, we demonstrated a significant rise in non-protocolized use over the last decade. This study uses qualitative methods to provide the first report of how clinicians understand, approach, and apply CysC testing in inpatient care. Methods Fifteen clinicians from various disciplines were interviewed about their experience with inpatient CysC testing. The semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed thematically using a phenomenological approach. Results Knowledge and confidence with CysC varied greatly. Clinicians reported first learning about the test from colleagues on consulting services or multidisciplinary teams. The majority believed CysC to provide a more accurate measure of kidney function than SCr. Common scenarios for CysC ordering included medication dosing, evaluation of acute kidney injury, and a thorough evaluation of kidney function in patients with risk factors for an altered SCr. Facilitators for ordering CysC included the availability of rapid results turnaround and the automated calculation of glomerular filtration rate based on the biomarker. Barriers to use included a lack of education about CysC, and the absence of an institutional protocol for use. Discussion Clinicians at our site decided independent of institutional guidance whether and when CysC added value to patient care. While the majority of study participants indicated advantages to rapid turnaround CysC testing, its use depended not just on the features of the specific case but on clinician familiarity and personal preference. Findings from this research can guide the implementation and expansion of CysC testing.

Abstract P026: The Accumulation Of Lysine In The Kidney Cortex Protects From Proximal Tubule Damage And Salt-Sensitive Hypertension.

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Oleg Palygin ◽  
Markus Rinschen ◽  
Vladislav Levchenko ◽  
Denisha Spires ◽  
Gary Siuzdak ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Amino Acids ◽  
Proximal Tubule ◽  
Kidney Function ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Essential Amino Acids ◽  
Treated Group ◽  
Kidney Cortex ◽  
Salt Sensitive Hypertension

The kidneys are highly sensitive to metabolic changes. Metabolic phenotyping uncovered a number of pathways associated with high blood pressure and kidney diseases, which sheds light on the complex pathophysiology of hypertension and associated kidney injury. However, the mechanisms underlying the effects of dietary interventions on kidney function and associated changes in cellular metabolic intermediates remain incompletely understood. L-lysine, one of the essential amino acids, is necessary for many physiological functions. Among all organs, the kidney is a key organ in lysine turnover and metabolism, in particular for modified lysines. Our recent metabolomics study revealed that intrarenal levels of L-Lysine are reduced in Dahl salt-sensitive (SS) rats fed an HS diet. This finding provided further evidence that L-Lysine is critical for metabolic states in the kidney. Using a well-established SS rat model of hypertension and kidney injury, we found that administration of lysine at a concentration of 17mg/ml in drinking water counteracted the lysine deficit in kidneys, restored albumin balance, triggered diuresis, and diminished the development of salt-sensitive hypertension (133±2 vs. 165±4 (136±4 vs. 166±7), mmHg in L-Lysine treated rats vs. control rats male (female) after 14 (21) days of an 8 (4) % NaCl diet). HPLC analysis revealed a significant elevation of lysine in the renal cortex of treated rats. In contrast, the concentration of other amino acids, such as glycine and arginine, did not change with increasing blood pressure. Overall, dietary lysine supplementation of SS rats on the HS diet leads to significant protection of proximal tubule damage, shown by Kim-1 immunostaining. Also, it restores kidney function by the rapid excretion of the pathologically accumulated renal albumin and rebalancing megalin abundance. Moreover, the analyses of glomerular damage showed improvement for the lysine treated group. In conclusion, dietary L-Lysine supplementation significantly enhanced cardiorenal protection via acute inhibition of metabolic load and oxidative stress triggered by hypertension.

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