Progression Of Chronic Renal Disease Research Articles

#1626 The role of sodium-glucose cotransporter 2 inhibitors in diabetic nephropathy and non diabetic renal disease in diabetes mellitus type 2 patients

Abstract Background and Aims Diabetes Mellitus type 2 (DM2) leads to chronic kidney disease in a 30-40% of diabetic patients and it is the major cause of end stage renal disease (ESRD). The clinical course of diabetic kidney disease is very heterogeneous and there is a lack of agreement between clinical parameters and renal histology. Besides, lesions of non-diabetic kidney disease (NDRD) can coexist with lesions of diabetic nephropathy (DN) in two-thirds of kidney biopsies in patients with diabetes. There is not a specific treatment against diabetic kidney disease, treatment based in the blockade of renin-angiotensin-aldosterone system has demonstrated a delay of kidney function decline but the diabetic kidney disease is still the main cause of renal replacement by dialysis. Recently, a new class of oral glucose -lowering drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, have shown beneficial effects into cardiovascular protection and chronic kidney disease in diabetic patients but it is not clear the beneficial effect in DN. The aim of this study is to evaluate the role of SGLT2 inhibitors in diabetic patients with DN biopsy-confirmed and compare with a group of diabetic patients with NDRD (DN and superimposed non diabetic renal disease lesions, NDRD). Method This is a retrospective study with DM2 patients and kidney biopsy performed. Patient demographic characteristics were recorded and diagnosis of Hypertension, duration of DM2, presence or absence of diabetic retinopathy (DR), macrovascular disease and treatment with renin–angiotensin– aldosterone system blockers (RAASB), oral hypoglycaemic agents, insulin, and aldosterone antagonists. Histological lesions were recorded according to the pathologic classification of DN. Renal function was based on estimated filtration rate CKD-EPI (eGFR mil/min/m2), the urine albumin-creatinine ratio (UACR mg/gr) and the 24 h proteinuria (g/24 h). Diabetic patients were classified according to the kidney biopsies in DN and NDRD. The follow up was assessed at the time of sodium-glucose cotransporter 2 (SGLT2) inhibitors started, 6, 12 and 24 months. Results A total of 64 DM2 patients with kidney biopsy were included in the study. Basal characteristics are summarized in Table 1. DN was diagnosed in 47% and NDRD in 53% of DM2 patients. DM2 patients with NDRD were older (64 ± 10 vs 70 ± 10, p = 0.017), and with more macrovascular disease than patients with DN, 6 (20%) vs 15 (44%), p = 0.04. Instead, DM2 patients with DN showed higher uACR levels than NDRD (2355 ± 2540 vs 706 ± 730, p = 0.02). A 40% of DM2 patients with DN were classified in nodular sclerosis class III of glomerular classification of DN. Interstitial fibrosis and tubular atrophy score were higher in DN versus NDRD patients, (interstitial fibrosis 12 (40%) vs 3 (9%), p = 0.006, tubular atrophy 10 (33%) vs 3 (9%), p = 0.02, Table 2. At the end of follow up, 20% of DM2 patients developed ESRD. According SGLT2 inhibitors treatment, a higher proportion of ESRD and death were observed in DM2 patients without SGLT2 inhibitors than patients with SGLT2 inhibitors, ESRD 11 (39%) vs 2 (6%), p = 0.001, death 9 (32%) vs 4 (11%), p = 0.03. Serum creatinine levels were lower in DM2 patients with SGLT2 inhibitors (118 ± 63.7 vs 203 ± 80.7, p = 0.001), but no differences was observed in uACR between groups. A significant reduction in serum creatinine levels with better eGFR were observed in both groups (DN and NDRD) under SGLT2 inhibitors comparing to group without SGLT2 inhibitors, serum creatinine levels 124 ± 78 vs 236 ± 83, p = 0.008, 107 ± 40 vs 201 ± 110, p = 0.02, and eGFR mil/min/m2 60.9 ± 27.5 vs 25.1 ± 7.2, p = 0.004, 62.6 ± 21.2 vs 33.7 ± 16.2, p = 0.005, Table 3. Conclusion A higher proportion of DM2 showed NDRD lesions in kidney biopsy. Treatment with SGLT2 inhibitors reduced progression of chronic renal disease in DN and NDRD DM2 patients. A reduced progression to ESRD and death were also observed in NDRD DM2 patients with SGLT2 treatment.

Herbal Components for the Treatment of Various Kidney Disorders

Abstract:: Acute kidney injury is described as a loss of renal excretory function that occurs suddenly. AKI is one of several ailments grouped together as acute kidney diseases and disorders (AKD), in which progressive degradation of kidney function or persistent renal dysfunction is associated with irreversible loss of kidney cells and nephrons, potentially leading to chronic kidney disease (CKD). The prevalence and incidence of KDs are assessed in light of population disparities in the prevalence of risk factors such as diabetes, hypertension, and obesity. However, the presence of these associated illnesses does not fully explain the increased rate of progression of chronic renal disease in high-risk patients (CKD). The development of renal disease is accompanied by a decline in renal function, which eventually leads to renal failure. The current status of diagnostic testing does not allow for accurate early disease diagnosis, prognosis, or therapy efficacy monitoring. Despite significant advances in care and understanding of the causes of acute renal failure (ARF), many aspects of ARF remain controversial, confusing, and uncertain. Accurate information on the disease's prevalence, genesis, and clinical manifestations is required to successfully advocate for enough funding and resources to manage the disease. Herbal components for the treatment of a variety of kidney disorders, and the page includes a list of plants that are good for kidney treatment. This review focuses on several herbal products used to treat renal problems. It is clear from this study that medicinal plants play an important role in the fight against many different diseases. Several different plants and plant extracts have been shown to have beneficial effects in treating renal disease. These medications have great promise for use in treating kidney damage because of their nephroprotective, cytoprotective, immunomodulatory, antioxidant, anti-inflammatory, and reducing effects on oxidative stress, renal hypertension, and blood toxins such as urea, creatinine, and others. Therefore, India's traditional medicine offers a wide variety of medications that can be utilized in renal illnesses due to their effectiveness in both treating the ailment and restoring normal kidney function. Therefore, it is suggested that additional research be conducted to learn many aspects and mechanisms of medications.

The roles of heme oxygenase-1 in renal disease.

Heme oxygenase (HO), a heat shock protein containing hemoglobin, is an important enzyme in heme catabolism. It is involved in cell homeostasis and has anti-inflammatory, antioxidant, anti-apoptosis, immunomodulation, and other functions. It is expressed at a modest level in most normal tissues. When the body suffers from ischemia hypoxia, injury, toxins, and other nociceptive stimuli, the expression increases, which can transform the oxidative microenvironment into an antioxidant environment to promote tissue recovery from damage. In recent years, research has continued to verify its value in a variety of human bodily systems. It is also regarded as a key target for the treatment of numerous disorders. With the advancement of studies, its significance in renal disease has gained increasing attention. It is thought to have a significant protective function in preventing acute kidney injury and delaying the progression of chronic renal diseases. Its protective mechanisms include anti-inflammatory, antioxidant, cell cycle regulation, apoptosis inhibition, hemodynamic regulation, and other aspects, which have been demonstrated in diverse animal models. Furthermore, as a protective factor, its potential therapeutic efficacy in renal disease has recently become a hot area of research. Although a large number of preclinical trials have confirmed its therapeutic potential in reducing kidney injury, due to the problems and side effects of HO-1 induction therapy, its efficacy and safety in clinical application need to be further explored. In this review, we summarize the current state of research on the mechanism, location, and treatment of HO and its relationship with various renal diseases.

Anti-inflammatory and nephroprotective influence of virgin coconut oil on gentamicin‐induced nephrotoxicity in non-diabetic and streptozotocin-induced diabetic rats

Gentamicin is an effective antibiotic against severe infections, but a major downside is its nephrotoxic effects. Virgin coconut oil has potential antidiabetic effects, but there has been no study on its potential role in gentamicin‐induced nephrotoxicity in streptozotocin -induced diabetic rats. Thus, the aim of the current study is to explore the anti‐inflammatory and nephroprotective effects of virgin coconut oil on non-diabetic and streptozotocin-induced diabetic rats. A total of 48 adult male Sprague-Dawley rats were randomly divided into eight groups (n=6), including non-diabetic groups (groups 1-4) and streptozotocin-induced diabetic groups (groups 5-8). Groups 1 and 5 received a normal diet, groups 2 and 6 were fed a normal diet + gentamicin at 100 mg/kg/day for the last 10 days of the study period, groups 3 and 7 were treated with 10 ml/kg/day of virgin coconut oil for four weeks, and groups 4 and 8 were given gentamicin for the last 10 days of the study period plus virgin coconut oil for four weeks at the same doses mentioned. Gentamicin adminstaration caused oxidative stress, and led to antioxidant defense depression which was confirmed by elevated kidney Malondialdehyde (MDA) (4.53, 5.62) and reduced renal antioxidant enzymes including renal superoxide dismutase (59.82, 45.58), catalase (53.11, 37.3) and glutathione peroxidase (51.41.36.34) in non-diabetic (ND) and diabetic (D) rats, respectively. It also resulted in a significant increase of serum urea (31.72, 50.78), creatinine (2.88, 4.16), cystatin-C (13.75, 17.69), and inflammatory biomarkers interleukin-6 (IL-6) (84.01, 102.73) and tumor necrosis factor-α (TNF-α) (667.05, 853.05) in ND and D rats, respectively. Virgin coconut oil showed protective effects and significantly improved renal function parameters, including serum urea (17.35, 38.9), creatinine (1.69, 2.96) and cystatin-C (14.26, 15.94) for ND and D groups, respectively. Pre- and co-administration of virgin coconut oil exerted a remarkable protective effect against oxidative stress induced by gentamicin in normal and diabetic rats. Pro-inflammatory biomarkers were also improved in groups treated with virgin coconut oil. The results are promising in terms of the use of virgin coconut oil as a dietary agent in attenuating the progression of chronic renal disease, especially in the context of diabetes. Key words: anti‐inflammatory, nephroprotective, virgin coconut oil, gentamicin, streptozotocin, flavonoid, phenol, oxidative stress

Renoprotective Impacts of Inonotus obliquus Ethanol-Ethyl Acetate Extract on Combined Streptozotocin and Unilateral Nephrectomy-Induced Diabetic Nephropathy in Mice

Diabetes nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) globally. Medication options to stop or slow the progression of chronic renal disease (CKD) are limited, and patients with DN remain at a high risk of developing renal failure. Inonotus obliquus extracts (IOEs) of Chaga mushroom have been shown to have anti-glycemic, anti-hyperlipidemia, antioxidant, and anti-inflammatory effects against diabetes. In this study, we examined the potential renal protective role of an ethyl acetate layer after water-ethyl acetate separation from Inonotus obliquus ethanol crude extract (EtCE-EA) from Chaga mushrooms in diabetic nephropathy mice after preparation with 1/3 NT + STZ. Our data showed that treatment with EtCE-EA can effectively regulate blood glucose, albumin-creatinine ratio, serum creatinine, and blood urea nitrogen (BUN) levels, and it can improve the renal damage in 1/3 NT + STZ-induced CRF mice with an increase in concentration (100, 300, and 500 mg/kg). In the immunohistochemical staining test, EtCE-EA can effectively reduce the expression of TGF-β and α-SMA after induction according to the increase in the concentration (100 mg/kg, 300 mg/kg), thereby slowing down the degree of kidney damage. Our findings demonstrate that EtCE-EA could provide renal protection in diabetes nephropathy, possibly due to the decreased expression of transforming growth factor-β1 and α-smooth muscle actin.

Lupus nephritis: from diagnosis to treatment

Renal involvement in systemic lupus erythematosus (SLE), so-called lupus nephritis (LN), is one of the most frequent organ manifestations with an incidence of approximately 40-60%. It is not uncommon for renal involvement to be the initial manifestation of SLE or to occur in the first 5-10years after diagnosis of SLE. Urinalysis is useful in screening for the presence of LN, demonstrating proteinuria or active sediment with acanthocytes. Histologic confirmation of LN, and thus the LN class present, is currently the gold standard for confirming the diagnosis. In addition, knowledge of the LN class is arelevant component of adequate treatment planning in SLE patients with LN. In particular, early diagnosis and rapid response to therapy are of prognostic importance for the preservation of renal function as well as morbidity and mortality of the mostly young patients at the time of initial diagnosis. Thus, the focus of therapy is to achieve complete remission, as well as to avoid active disease phases. Due to acomplex pathogenesis and at the same time avery heterogeneous clinical presentation, with six different histological classes of LN, there are different therapeutic targets. This in turn results in asignificant expansion of the study landscape in the field of LN with an increasing understanding of the signaling pathways and influencing factors, and fortunately in agrowing armamentarium of available targeted therapy options. Simultaneously, new insights into drug therapy to inhibit progression of chronic renal disease are opening up supportive therapy options that can further improve preservation of renal function.

Biomolecular Mechanisms of Cardiorenal Protection with Sodium-Glucose Co-Transporter 2 Inhibitors.

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia and associated with an increased risk of morbidity and mortality, primarily from cardiovascular and renal diseases. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are novel drugs for the treatment of type 2 DM and heart failure (HF). SGLT2-Is mediate protective effects on both the renal and cardiovascular systems. This review addresses the current knowledge on the biomolecular mechanisms of the cardiorenal protective effects of SGLT2-Is, which appear to act mainly through non-glucose-mediated pathways. Cardiorenal protection mechanisms lead to reduced chronic renal disease progression and improved myocardial and coronary endothelial function. Concomitantly, it is possible to observe reflected changes in biomarkers linked with diabetic kidney disease and HF.

Protein intake, chronic renal disease progression and cardiovascular morbidity.

It has been suggested that the lowering of dietary protein reduces the progression of CKD, despite it has been also reported that higher intake of total protein was associated with a lower risk of cardiovascular morbidity.The role of protein intake is equivocal in clinical outcomes including the renal and cardiovascular disease worsening, metabolic acidosis and bone abnormalities.The modification of both amount and sources of protein intake could influence the renal and cardiovascular deterioration.

Hyperuricemia in Patients with Chronic Renal Failure: A Single Center Study, Pakistan

Introduction: a level of serum uric acid more than or equal to 70 mg/l (420 mol/l) in males and 60 mg/l (360 mol/l) in women is considered hyperuricemia. It has been established in many studies to be a risk factor or a factor in the progression of chronic renal disease. Recent experimental and epidemiological studies link hyperuricemia to chronic kidney disease (ckd), arterial hypertension, and cardiovascular disease, raising the issue of whether medicines are effective in the prevention of renal illness. The goal of this study is to discover whether there is a relationship between chronic renal disease and hyperuricemia. Methodology: From january 1st to december 1st, 2015, this single-center study was done at the department of nephrology at marcy teaching hospital in peshawar, pakistan (12 months). We included all chronic renal disease patients with associated hyperuricemia who were admitted to a hemodialysis unit. Results: A total of 72 individuals were included in the study. The prevalence of hyperuricemia was 15.20 percent. The average age of the patients was 35.5 years. The age group of 40 to 60 years old accounted for 54.6 percent of the total. Patients with hypertension accounted for 49% of the total, with diabetes and hypertension being linked in 11% of the cases. In 42.3 percent of patients, renal insufficiency was moderate. In more than 90% of the patients, hyperuricemia was found. Hyperuricemia was statistically linked to profession, age, hematuria, proteinuria, and hypertension. In 85 percent of patients, allopurinol was prescribed as a treatment. More than 12% of patients had an unsatisfactory course of treatment. Conclusion: Several recent investigations have shown the role of hyperuricemia in chronic renal disease. To determine its true influence on the prevention and treatment of chronic renal disease, randomised study on large sizes must be conducted. Keyword: A Single Center Study, Hyperuricemia, Chronic Renal Failure

Evaluation of circulatory microRNA-196 levels during the progression of chronic renal (kidney) disease of unknown etiology

Chronic renal disease of unknown etiology is prevalent & clinically silent until its late stages at which point patients may suffer significant irreversible damage or mortality in the lack of early screening & intervention. If diagnosed early stage 1-3 the progression of chronic renal disease can be altered and complications reduced. Current diagnosing markers of renal function, serum creatinine, blood urea and uric acid have been shown to be lacking high predictive value. So, there is a need for next generation biomarkers suitable for Chronic renal disease of unknown etiology and should not be influenced by age, sex, nutritional status, current health concern. microRNAs appears to be very stable in tissues & biological fluids even under adverse conditions like extreme pH, long term room temperature storage, multiple freeze thaw cycles & RNAase activity. microRNAs elaborate in renal development, maintenance of renal function & progression of renal disease. miRNA-196 is a renal derived biomarker, extensively distributed in renal, shows an important role in renal diseases & superior to other renal biomarkers. The aim of present study is to evaluate circulatory miRNA-196 during progression of chronic renal disease of unknown etiology.

CD137L-macrophage induce lymphatic endothelial cells autophagy to promote lymphangiogenesis in renal fibrosis

Renal lymphangiogenesis is a new field of international nephrology in recent years and plays an important role in the progression of chronic renal disease. CD137 was originally described as a surface molecule present on activated T and NK cells and detected on hypoxic endothelial cells and inflamed blood vessels, but its function on lymphatic endothelial cells remains unclear. We investigated the relationships among CD137, lymphangiogenesis and macrophages, which are involved in interstitial fibrosis. Similar to other chronic inflammatory diseases, we found lymphangiogenesis and expression of CD137 in the renal tissue of patients with IgA nephropathy. CD137-positive lymphatic vessels were involved in the development process of IgA nephropathy and positively correlated with serum creatinine, serum urea nitrogen, serum uric acid, and urinary 24 h total protein. The expression of these indicators was negatively correlated with eGFR, plasma albumin, and HB. In mouse models of UUO, we verified that CD137 expression was significantly elevated during lymphangiogenesis and that its ligand CD137L was released by macrophages after VEGF-C stimulation in the kidney. In vitro, recombinant CD137L significantly enhanced LEC proliferation, migration and tube formation, and these effects were inhibited by CD137 siRNA. Mechanistically, the CD137L interaction with CD137 induced the transition from LC3-I to LC3-II and the expression of Atg5, Atg7, Atg12 and p62 proteins by activating the PI3K/AKT/mTOR pathway to promote autophagy. Knockdown of Atg5 and Atg7 blocked CD137L-induced autophagy. Thus, we propose that CD137L secretion by macrophages interacts with CD137 on lymphatic endothelial cells to prompt lymphangiogenesis in the kidney, which further drives fibrogenic responses. Our findings suggest that inhibition of the CD137-CD137L pathway is a novel therapeutic approach for obstructive nephropathy.

Sex-differences in initiation of renin-angiotensin system inhibitors in patients with type 2 diabetes diagnosed with albuminuria

Abstract Background Renin-angiotensin system inhibitors (RASi) are the preferred drug of choice in patients with type 2 diabetes (T2D) and albuminuria to prevent progression of chronic renal disease and cardiovascular complications. However, it is unknown whether sex-differences exist in the initiation of RASi in patients with T2D and albuminuria, and potential sex-differences in the effect of RASi on all-cause death in these patients remains untested. Purpose To examine potential sex-differences in the initiation of RASi in patients with T2D and albuminuria, and secondly whether these sex-differences are associated with mortality risk. Methods Using Danish nationwide registers, we included patients with their first albumin-creatinine ratio (ACR; index date) of ≥30 mg/g between 1 January 2014 and 20 March 2019 in patients with T2D with no prior end-stage renal disease, no acute renal failure within 90 days, and no claimed prescriptions of RASi within 15 years. We used multiple Cox regression to study the hazard ratio (HR; men vs women) of 30-day RASi initiation. In 30-day survivors, we used another multiple Cox regression to compare mortality between patients who initiated RASi and patients who did not yet initiate RASi. Reported were the sex-specific standardized 1-year risk differences for fixed comorbidity distribution according to RASi treatment. Results In 20,440 patients (44% women), 1,190 men and 682 women initiated RASi treatment within 30 days after index. The adjusted rate of RASi initiation was higher in men compared to women (HR 1.34 [1.22; 1.48]). This association was observed regardless of hypertension (no: HR 1.35 [1.20; 1.52]; yes: HR 1.34 [1.14; 1.57]) and ACR-group ((30–300] mg/g: HR 1.35 [1.22; 1.49]; ≥300 mg/g: HR 1.30 [0.98; 1.73]), although borderline significant for ACR ≥300 mg/g (p=0.071). The association declined with descending estimated glomerular filtration rate (eGFR) and was not significant for eGFR group (15–60] (eGFR (90–120]: HR 1.45 [1.28; 1.65]; (60–90]: HR 1.25 [1.06; 1.47]; (15–60]: HR 1.07 [0.77; 1.48]). 30 days after index, 49 patients (37% women) had died, and 9 patients (33% women) had emigrated. In 30-day survivors, the standardized 1-year mortality risk was 1.9% [1.4; 2.4] in men who readily initiated RASi, and 3.3% [3.0; 3.7] in men who did not (absolute reduction: 1.5% [0.9; 2.0]). In contrast, the absolute reduction was not significant in women (0.1% [−0.5; 0.8]). Standardizing according to sex, the associated 1-year mortality risk was 3.4% [3.1; 3.7] in men without RASi, and 2.8% [2.5; 3.0] in women (absolute risk difference 0.6% [0.3; 0.9]). In contrast, men with RASi were borderline significantly associated with a lower 1-year mortality risk compared to women with RASi (absolute risk difference 0.8% [0.0; 1.5], p=0.042). Conclusions In patients with T2D and albuminuria, men are more likely to initiate RASi within 30 days, and RASi appears to be associated with greater benefit on 1-year mortality risk in men. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Figure 1Figure 2

Гипоксия — ведущий фактор прогрессирования хронической болезни почек

Современные данные свидетельствуют об участии гипоксии в процессе формирования фиброза в почках и прогрессирования хронической болезни почек. Одним из основных факторов в цепочке повреждения при тканевом дефиците кислорода является индуцированный гипоксией фактор. Понимание процесса повреждения почки при гипоксии может дополнить представление о нефропротекции пациентов с хронической болезнью почек, даст возможность улучшить рекомендации по ведению данной группы больных.

Static and Dynamic Prediction of Chronic Renal Disease Progression Using Longitudinal Clinical Data from Taiwan's National Prevention Programs.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3–5 kidney disease who were treated at a public veteran’s hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3–5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b–5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b–5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented.

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review).

KIM-1 (kidney injury molecule 1) is a transmembrane glycoprotein also known as HAVcr-1 and TIM-1 belongs to the T-cell immunoglobulin and mucin domain family (TIM) of proteins. TIM glycoproteins are presented on the immune cells and participate in the regulation of immune reactions. KIM-1 differs from other members of its family in that it is expressed not only by immunocompetent cells but epithelial cells as well. Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes.Current understanding of the mechanisms determining the participation of KIM-1 in viral invasion, the immune response regulation, adaptive reactions of the kidney epithelium to acute ischemic or toxic injury, in progression of chronic renal diseases, and kidney cancer development have been presented in this review. Data of clinical researches demonstrating the association of KIM-1 with viral diseases and immune disorders have also been analyzed. Potential application of KIM-1 as urinary or serological marker in renal and cardiovascular diseases has been considered.

CD4+CD28 Null T Cells as a Marker of Progression in Chronic Renal Disease Including Hemodialysis Patients and Its correlation with Systemic Inflammation and Atherosclerosis.

CD4+CD28 Null T Cells as a Marker of Progression in Chronic Renal Disease Including Hemodialysis Patients and Its correlation with Systemic Inflammation and Atherosclerosis.

POS-304 EFFECT OF URIC ACID LOWERING THERAPY ON THE PROGRESSION OF CKD: RETROSPECTIVE TUNISIAN STUDY

Hyperuricemia (HU) has been considered to be associated with adverse outcomes in CKD due to reduced glomerular filtration rate. Recently, some studies have suggested that HU is an independent risk factor for renal disease progression. However, whether uric acid-lowering therapy can retard the progression of CKD is unclear. The aim of our study is to assess the effect of treatment in the progression of chronic renal disease as well as the transition to chronic renal failure.

Effect of HIF1α on the TRPC6 channel of glomerular podocytes under chronic hypoxia

BackgroundChronic hypoxia plays an important role in the initiation and progression of chronic renal disease. The pathogenic role of chronic hypoxia in tubulointerstitial injury has been investigated widely, but little is known about acute hypoxia implications in glomerular damage. In this study, we investigated the effect of chronic hypoxia on transient receptor potential cation channel 6 (TRPC6) and the underlying mechanism in cultured human podocytes. MethodsFluo-3 was used as a calcium indicator of the OAG-induced receptor operated calcium entry (ROCE) and basal [Ca2+]i levels were monitored using laser scanning confocal microscope after exposure of cells to chronic hypoxia. 2-aminoethoxydiphenylborane (2-APB), a pharmacological blocker of TRPCs channels, was used to determine the role of TRPC6 in podocytes under chronic hypoxia. The mRNA expression and protein levels of TRPC6 were determined using Real-time RT-PCR and Western Blotting under normoxic and chronic hypoxic conditions. Actin arrangement was analyzed by confocal microscopy using phalloidin staining of F-actin in podocytes. ResultsCytosolic free Ca2+ was increased by hypoxia or the treatment of TRPC6 agonist OAG under normoxic conditions. The increase of intracellular Ca2+ induced by hypoxia was time- and dose-dependent, which can be inhibited by 2-APB, demonstrating that the changes of intracellular Ca2+ induced by OAG depend on the activation of TRPC6. Further study showed that the TRPC6 expression levels were significantly increased by hypoxia, which were inhibited by the HIF1α inhibitor in podocytes. Similarly, the increase of intracellular Ca2+ induced by hypoxia was decreased when the podocytes were incubated with HIF1α inhibitor. We also found that F-actin was ruptured by hypoxia in podocytes, showing cytoskeleton reorganization. ConclusionsTRPC6 mRNA and protein expression levels were significantly increased in podocytes under hypoxia, which may result in the increase of intracellular Ca2+. This alternation of TRPC6 may be relevant to the modulation of HIF1α. Hypoxia in podocytes can result in cytoskeleton reorganization, which further leads to podocytes injury and disfunction.

Unusual splenic B-cell lymphoma in two related Sumatran tigers (Panthera tigris sumatrae)

A 14-year-old 120-kg (264-lb) sexually intact male Sumatran tiger (Panthera tigris sumatrae) and its 10-year-old 130-kg (286-lb) sexually intact male offspring were housed separately and evaluated independently after experiencing weeks of ongoing malaise, weight loss, and anorexia. Both animals were immobilized and anesthetized for physical examinations and diagnostic testing. Complete blood counts revealed leukopenia and anemia in both tigers. Splenomegaly was identified on abdominal ultrasonography. Cytologic examination and immunohistochemical staining of splenic samples confirmed intermediate to large B-cell lymphoma; no evidence of lymphoma in surrounding organs was noted. The sire was treated with lomustine and prednisolone. This tiger was euthanized 21 months after initiation of treatment because of chronic progressive renal disease. The male offspring was treated with l-asparaginase but did not respond to the treatment. A splenectomy was performed, and malaise and anorexia resolved. No further chemotherapy was administered, and the male offspring was instead maintained on a low dose of prednisolone. Thirty-two months after diagnosis, the male offspring was still considered to be in remission. To our knowledge, this was the first known report of the diagnosis and management of a splenic B-cell lymphoma in a tiger. Both tigers achieved positive clinical responses and long-term survival by means of different treatment modalities. The finding of such an unusual neoplasm in a male tiger and its male offspring was noteworthy, raising the possibility of a genetic predisposition for this lymphoma type.

Découverte fortuite d’une atteinte hépatique d’amylose à leukocyte chemotactic factor 2

Leukocyte cell-derived chemotaxin 2-associated amyloidosis (ALECT2) is a recently described of amyloidosis described in the United States in 2007. It is a systemic disease that is predominantly associated with some ethnics groups. ALECT2is usually diagnosed on a kidney biopsy performed in the context of slowly progressive chronic renal disease but can also be found incidentally on a liver sample. We report the case of a Syrian patient who benefited from a partial hepatectomy for the treatment of multiple metastasis of a colorectal adenocarcinoma. Microscopic analysis of the surgical specimen revealed numerous amyloid deposits that did not match any of the usual forms of liver amyloidosis after immunohistochemistry typing. Some morphologic features of the deposits were highly suggestive of ALECT2. Complementary immunohistochemical study and mass spectrometry confirmed the diagnosis.