scholarly journals A Sodium Oxalate-Rich Diet Induces Chronic Kidney Disease and Cardiac Dysfunction in Rats

2021 ◽  
Vol 22 (17) ◽  
pp. 9244
Author(s):  
Thayane Crestani ◽  
Renato O. Crajoinas ◽  
Leonardo Jensen ◽  
Leno L. Dima ◽  
Perrine Burdeyron ◽  
...  

Chronic kidney disease (CKD) is a worldwide public health issue affecting 14% of the general population. However, research focusing on CKD mechanisms/treatment is limited because of a lack of animal models recapitulating the disease physiopathology, including its complications. We analyzed the effects of a three-week diet rich in sodium oxalate (OXA diet) on rats and showed that, compared to controls, rats developed a stable CKD with a 60% reduction in glomerular filtration rate, elevated blood urea levels and proteinuria. Histological analyses revealed massive cortical disorganization, tubular atrophy and fibrosis. Males and females were sensitive to the OXA diet, but decreasing the diet period to one week led to GFR significance but not stable diminution. Rats treated with the OXA diet also displayed classical CKD complications such as elevated blood pressure and reduced hematocrit. Functional cardiac analyses revealed that the OXA diet triggered significant cardiac dysfunction. Altogether, our results showed the feasibility of using a convenient and non-invasive strategy to induce CKD and its classical systemic complications in rats. This model, which avoids kidney mass loss or acute toxicity, has strong potential for research into CKD mechanisms and novel therapies, which could protect and postpone the use of dialysis or transplantation.

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3617
Author(s):  
Fabrizio Fabrizi ◽  
Roberta Cerutti ◽  
Carlo M. Alfieri ◽  
Ezequiel Ridruejo

Chronic kidney disease is a major public health issue globally and the risk of cancer (including HCC) is greater in patients on long-term dialysis and kidney transplant compared with the general population. According to an international study on 831,804 patients on long-term dialysis, the standardized incidence ratio for liver cancer was 1.2 (95% CI, 1.0–1.4) and 1.5 (95% CI, 1.3–1.7) in European and USA cohorts, respectively. It appears that important predictors of HCC in dialysis population are hepatotropic viruses (HBV and HCV) and cirrhosis. 1-, 3-, and 5-year survival rates are lower in HCC patients on long-term dialysis than those with HCC and intact kidneys. NAFLD is a metabolic disease with increasing prevalence worldwide and recent evidence shows that it is an important cause of liver-related and extra liver-related diseases (including HCC and CKD, respectively). Some longitudinal studies have shown that patients with chronic hepatitis B are aging and the frequency of comorbidities (such as HCC and CKD) is increasing over time in these patients; it has been suggested to connect these patients to an appropriate care earlier. Antiviral therapy of HBV and HCV plays a pivotal role in the management of HCC in CKD and some combinations of DAAs (elbasvir/grazoprevir, glecaprevir/pibrentasvir, sofosbuvir-based regimens) are now available for HCV positive patients and advanced chronic kidney disease. The interventional management of HCC includes liver resection. Some ablative techniques have been suggested for HCC in CKD patients who are not appropriate candidates to surgery. Transcatheter arterial chemoembolization has been proposed for HCC in patients who are not candidates to liver surgery due to comorbidities. The gold standard for early-stage HCC in patients with chronic liver disease and/or cirrhosis is still liver transplant.


2013 ◽  
Vol 304 (7) ◽  
pp. C591-C603 ◽  
Author(s):  
Gabriela Campanholle ◽  
Giovanni Ligresti ◽  
Sina A. Gharib ◽  
Jeremy S. Duffield

Chronic kidney disease, defined as loss of kidney function for more than three months, is characterized pathologically by glomerulosclerosis, interstitial fibrosis, tubular atrophy, peritubular capillary rarefaction, and inflammation. Recent studies have identified a previously poorly appreciated, yet extensive population of mesenchymal cells, called either pericytes when attached to peritubular capillaries or resident fibroblasts when embedded in matrix, as the progenitors of scar-forming cells known as myofibroblasts. In response to sustained kidney injury, pericytes detach from the vasculature and differentiate into myofibroblasts, a process not only causing fibrosis, but also directly contributing to capillary rarefaction and inflammation. The interrelationship of these three detrimental processes makes myofibroblasts and their pericyte progenitors an attractive target in chronic kidney disease. In this review, we describe current understanding of the mechanisms of pericyte-to-myofibroblast differentiation during chronic kidney disease, draw parallels with disease processes in the glomerulus, and highlight promising new therapeutic strategies that target pericytes or myofibroblasts. In addition, we describe the critical paracrine roles of epithelial, endothelial, and innate immune cells in the fibrogenic process.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Pietro Manuel Ferraro ◽  
Alessandra Nicolosi ◽  
Alessandro Naticchia ◽  
Nicola Panocchia ◽  
Giuseppe Grandaliano ◽  
...  

Abstract Background and Aims Chronic kidney disease is a frequent condition, characterized, especially in its more advanced stages, by an array of derangements in bone structure and density, resulting in a higher rate of bone fractures. Current strategies to monitor the bone status and assess the risk of bone fractures in CKD patients are limited. The Bone Elastic Structure (BES) test is a recently-developed non-invasive tool that measures the elastic characteristics of the trabecular bone by simulating the application of loads on a virtual biopsy obtained from radiographic images of the proximal epiphyses in the patient’s hand fingers. The simulation results are combined to obtain a parameter defined Bone Structure Index (BSI). The aim of our study is to explore whether the BES test could be a useful monitoring tool of bone status in patients with CKD on dialysis by exploring whether such patients have different BSI values compared with persons without CKD. Method The BES test was performed on a sample of 41 patients undergoing chronic hemodialysis (HD) and the BSI compared with a group of 374 persons with normal renal function who had undergone the BES test in previous studies. Differences in BSI and 95% confidence intervals (CIs) between the two groups were obtained and tested for statistical significance with a linear regression model including BSI as the dependent variable and kidney status (HD vs no HD) as the independent variable, adjusted for age and sex. Subgroup effects were explored by including interaction terms (age x kidney status, age x sex, kidney status x sex) in the model. Finally, to further remove the potential confounding by age and sex, each HD patient was individually matched with up to 4 non-HD participants based on sex and age (with a 5-year caliper) and a matched analysis was conducted on BSI values. Results Average (SD) age was 64 (17) years in the HD group and 60 (12) years in the non-HD group, with a prevalence of males of 49% and 16%, respectively. The individual values of BSI divided by kidney status and sex in Figure. The multivariate linear regression model showed that, after adjustment for age and sex, the BSI in the HD group was significantly lower compared with the non-HD group (HD 145, 95% CI 140, 154; non-HD 179, 95% CI 177, 181; absolute difference −32, 95% CI −40, −25; p-value < 0.001). There was no significant interaction between age, sex and kidney status on BSI values (all p-values > 0.05). Individual matching was successful for 36 out of 41 HD patients, who were matched to 127 non-HD participants; matched analysis confirmed the results (absolute difference −31, 95% CI −40, −23; p-value < 0.001). Conclusion The output of a non-invasive tool to determine the bone elastic structure appeared to be strongly associated with kidney function after control for differences in age and sex. Further studies are needed to determine the potential application of the BES test in patients with CKD.


Author(s):  
Jing Liu ◽  
Maria Clarissa Tio ◽  
Ashish Verma ◽  
Insa M Schmidt ◽  
Titilayo O Ilori ◽  
...  

Abstract Context Abnormalities in calcium metabolism are common in chronic kidney disease (CKD). Diminished urinary calcium excretion may promote vascular calcification, and increased urinary calcium excretion may lead to nephrolithiasis and nephrocalcinosis, conditions associated with CKD. Objective To study predictors of urinary calcium excretion and its association with adverse clinical outcomes in CKD. Design, Setting and Patients This study assessed 3,768 non-dialysis participants in the Chronic Renal Insufficiency Cohort study from April 2003 to September 2008. Participants were followed up to October 2018. Exposure Clinically plausible predictors of urinary calcium excretion and 24-hour urinary calcium excretion at baseline. Main Outcome Measures Urinary calcium excretion; incident end stage kidney disease (ESKD), CKD progression (50% estimated glomerular filtration rate (eGFR) decline or incident ESKD), all-cause mortality, and atherosclerotic cardiovascular disease events. Results eGFR was positive correlated with 24-hour urinary calcium excretion. The variables most strongly associated with 24-hour urinary calcium excretion were 24-hour urinary sodium (β=0.19 and 0.28 in males and females), serum parathyroid hormone (β=-0.22 and -0.20), loop diuretics (β=0.36 and 0.26), thiazide diuretics (β=-0.49 and -0.53), and self-identified black race (β=-0.23 and -0.27). Lower urinary calcium excretion was associated with greater risks of outcomes, but these associations were greatly attenuated or nullified after adjustment for baseline eGFR. Conclusion Urinary calcium excretion is markedly lower in individuals with CKD compared to general population. Determinants of urinary calcium excretion differed between sexes and levels of CKD. Significant associations between urinary calcium excretion and adverse clinical events were substantially confounded by eGFR.


2015 ◽  
Vol 9 (1) ◽  
pp. 46-52
Author(s):  
Faruk Ahammad

Chronic kidney disease (CKD) is a global public health issue demanding continuous improvement in its management. Different international groups and organizations have now achieved a good progress in its definition, classification (staging), treatment and referral criteria to nephrologists. In definition of CKD, "CKD is defined as abnormalities of kidney structure or function, present for at least three months with implications for health", the phrase "with implications for health" has been added at the end of the previous definition, which reflects the concept that there may be certain abnormalities of kidney structure or function that do not have prognostic consequences (for example, a simple renal cyst). At staging of CKD, grade 3 has been subdivided into G3a and G3b, according to whether the glomerular filtration rate (GFR) is (59 - 45) or (44 - 30) ml/min/1.73m2, respectively. Furthermore, albuminuria has been classified in any GFR grade, in to A1, A2 or A3 according to the albumin-creatinine ratio (ACR) in an isolated urine sample for values <3, 3-30 or >30mg/mmol, respectively. The term "microalbuminuria" has now been replaced by the term "moderately increased albuminuria". For GFR measurement Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) equation has been preferred than the Modification of Diet in Renal Disease (MDRD) study equation and new 2012 KDIGO guidelines consider the use of alternative formulas to be acceptable if they have been shown to improve accuracy when compared with the CKD-EPI formula. For detection of albuminuria ACR is preferred rather than conventional 24 hours urine albumin. The recommended BP control target is ?140/90mmHg (both diabetic and non-diabetic) if ACR <3mg/mmol and a stricter target is suggested, with BP ?130/80mmHg, (both in diabetic and non-diabetic) if the ACR is ? 3mg/mmol. Use of erythropoisis-stimulating agent (ESA) in anemia of CKD should be rational; to avoid its adverse effects like stroke, thrombosis or hypertension acceleration and hemoglobin goals should not exceed 11 g per dl. Treating dyslipidaemia in CKD with statins for all adults >50 years of age, irrespective of low density lipoprotien (LDL) cholesterol levels is recommended. Referral to nephrologist should be rational according to guidelines and at least one year prior to the start of renal replacement therapy (RRT).Faridpur Med. Coll. J. 2014;9(1): 46-52


Author(s):  
L. I. Merkusheva ◽  
N. K. Runikhina ◽  
O. N. Tkacheva

Individuals age >65 years old are the fastest expanding population demographic throughout the developed world. Consequently, more aged patients than before are receiving diagnoses of impaired renal function and nephrosclerosis. In this review, we examine these features of the aged kidney and explore the various validated and putative pathways contributing to the changes observed with aging. Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to chronic kidney disease (CKD) in some individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitialfibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume. There is reason to be concerned that the elderly are being misdiagnosed with CKD. In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water -soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease.


2017 ◽  
Vol 12 (7-8) ◽  
pp. 293-301 ◽  
Author(s):  
Verica Kralj ◽  
Petra Čukelj

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
James M Kuczmarski ◽  
Christopher R Martens ◽  
Shannon L Lennon‐Edwards ◽  
David G Edwards

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