Effects Of Renal Damage Research Articles

The Mechanism of Hyperglycemia-Induced Renal Cell Injury in Diabetic Nephropathy Disease: An Update.

Diabetic Nephropathy (DN) is a serious complication of type I and II diabetes. It develops from the initial microproteinuria to end-stage renal failure. The main initiator for DN is chronic hyperglycemia. Hyperglycemia (HG) can stimulate the resident and non-resident renal cells to produce humoral mediators and cytokines that can lead to functional and phenotypic changes in renal cells and tissues, interference with cell growth, interacting proteins, advanced glycation end products (AGEs), etc., ultimately resulting in glomerular and tubular damage and the onset of kidney disease. Therefore, poor blood glucose control is a particularly important risk factor for the development of DN. In this paper, the types and mechanisms of DN cell damage are classified and summarized by reviewing the related literature concerning the effect of hyperglycemia on the development of DN. At the cellular level, we summarize the mechanisms and effects of renal damage by hyperglycemia. This is expected to provide therapeutic ideas and inspiration for further studies on the treatment of patients with DN.

P0020THE NEPHRO-PROTECTIVE ROUTE OF CGMP DOES NOT COMPENSATE NPRHOGENIC DIABETES INSIPIDUS, BOTH CONDITIONS MEDIATED BY RENAL INTEGRIN LINKED KINASE (ILK)

Abstract Background and Aims Renal ILK transgenic deletion on mice (cKD-ILK) address basal polyuria compatible with nephrogenic diabetes insipidus (NDI), due to disrupted tubular water channel aquaporin 2 (AQP2) AQP2 expression and vesicular trafficking to the apical membrane [Cano-Peñalver JL et al. FASEB J. 2014; Mamuya FA et al. Am J Physiol Renal Physiol. 2016]. An early symptom of chronic renal diseases (CKD) is NDI. ILK depletion also have a nephron-protective effect in renal damage in mice due to the increase in cGMP [Cano-Peñalver JL et al. Mol Med. 2016; de Frutos S et al. Biochim Biophys Acta Mol Basis Dis. 2019], the latter an alternative anti-NDI mediator. Here we demonstrate that ILK-mediated regulation of AQP2, under basal or CKD contexts, does not depend on cGMP. Method cKD-ILK and controls (WT) were treated orally with a NO donor, as precursor of cGMP formation (IDN, 300mg / Kg / day) for 24 hours. Urine volume was determined as a measure of tubular functionality. Fresh kidneys from non-treated mice were cultured ex vivo with precursors of cGMP (NO donor SNP, 1 µM or cGMP analogue 8Br-cGMP, 0.2 mM) for 30 minutes. AQP2 in the apical membrane of the tubules was quantified by immunohistochemistry. More cKD-ILK and WT were subjected for 6 weeks to a diet supplemented with 0.2% adenine (A) as CKD inducer or baseline standard diet. Urine volume and total ranal AQP2 levels were determined. Results Compared to WT, cGMP axis activation in vivo did not compensate the basal NDI present in cKD-ILK and the activation ex vivo did not improve the apical presence of AQP2 in cKD-ILK. Both WT and cKD-ILK subjected to CKD showed exacerbated polyuria and decreased levels of renal AQP2, but no differences were observed between groups. Conclusion ILK regulates AQP2, both in a basal and pathological context (CKD) independent of cGMP which otherwise is nephron-protective. Our results probably explain the co-existence of cGMP increase together with AQP2 decrease observed in the cKD-ILK kidneys.

Antidiabetic and Antinephropathic Potential of Ajwa Pit & Pulp (Phoenix dactylifera) in Alloxanized Diabetic Rats

Introduction: Generally in the world, diabetes is the most significant cause of deaths and morbidity. Blood glucose lowering agents possess remarkable adverse effects like weight gain and hypoglycemia and thus hindering the achievement of glycemic control. Since earliest times till today, herbal preparations have been utilized for management of diabetes and its complications. Aims & Objectives: To investigate antihyperglycemic and nephroprotective effects of Ajwa pit and pulp in alloxanized - diabetic and nephropathic rats. Place and duration of study: This study was conducted at Postgraduate Medical Institute, Lahore for the duration of four weeks. Material & Methods: Adult male rats (weighing 120-150 g), total of 32 were purchased and divided into 4 groups. The group1 was normal control whereas group2 was diabetic control. Diabetes was induced in groups 2, 3 and 4 with 150mg/kg single alloxan monohydrate1.P Injection. Groups 3 and 4 were given Ajwa pit and pulp rations for 4 weeks. Blood and urine samples were taken on zero and 4 weeks for fasting blood glucose, serum and urine biochemical variables for renal functions. Results: The results revealed that Ajwa pits significantly decreased serum levels of glucose (252±60 vs. 348±67 mg/dl), serum urea (38±7.0 vs. 63±9.6 mg/dl), serum creatinine (0.39±0.1 vs. 0.58±0.1 mg/dl) and microalbuminuria marker (7.8±1.7 vs. 9.0±2.2mg/l). Moreover it improved urine creatinine (14.0±2.9 vs.10.0±2.7 mg/dl) and creatinine clearance (0.226±0.08 vs 0.117±0.04 ml/min) when compared to diabetic control rats. Effect of Ajwa pulp was far less than Ajwa pit. Ajwa pulp did not significantly decrease serum levels of glucose (290±60 vs. 348±67 mg/dl), urea (51±9.5 vs. 63±9.6 mg/dl), creatinine (0.66±0.2 vs. 0.58±0.1 mg/dl) and microalbuminuria marker (8.3±2.0 vs. 9.0±2.2mg/l). Also there was no improvement in urine creatinine (11.1±1.6 vs. 10.0±2.7 mg/dl) and creatinine clearance (0.130±0.05 vs 0.117±0.04 ml/min) levels when compared to diabetic control rats. Conclusion: Ajwa pit possesses strong antihyperglycemic and protective effect in renal damage by prolonged diabetes mellitus. Highest polyphenols, bioflavonoids and antioxidants are presumed to be responsible for this effect.

Common Impact of Chronic Kidney Disease and Brain Microhemorrhages on Cerebral Aβ Pathology in SHRSP.

While chronic kidney disease seems to be an independent risk factor for cognitive decline, its impact on cerebral amyloid-β (Aβ) depositions, one hallmark of Alzheimer's Disease (AD) pathology, has not been investigated. Utilizing 80 male nontransgenic spontaneously hypertensive stroke prone rats (SHRSP) at various ages (12 to 44 weeks), tubulointerstitial renal damage, prevalence of cerebral microhemorrhages and Aβ accumulations were quantified. Using age-adjusted general linear models we investigated the main and interaction effects of renal damage and cerebral microhemorrhages on cerebral Aβ load. In addition, using post mortem human brain tissue of 16 stroke patients we examined the co-localization of perivascular Aβ deposits and small vessel wall damage. Statistical models revealed an age-independent main effect of tubulointerstitial kidney damage on brain Aβ accumulations, which was reinforced by the consecutive presence of cerebral microhemorrhages. Moreover, cerebral microhemorrhages independently predicted brain Aβ burden in SHRSP. In up to 69% of all human cases perivascular Aβ deposits were detected in the direct vicinity of small vessel wall damage. Our results support the associations between vascular pathology and Aβ deposition, and demonstrate a relationship between chronic kidney disease and cerebral Aβ pathology. Hence, our data suggest that prevention of chronic renal damage may reduce cerebral Aβ pathology.

THU0003 Effect of Renal Damage on Extra-Renal Organ Damage and Mortality in Patients with Systemic Lupus Erythematosus (SLE): A Longitudinal Cohort Study of 756 Patients

ObjectivesTo study the effect of renal damage on extra-renal organ damage and mortality in patients with SLE.MethodsPatients who fulfilled ≥4 ACR criteria for SLE between 1995 and 2011 were longitudinally...

The role of renal damage on cardiac remodeling in patients with diabetic nephropathy

Cardiovascular damage and diabetic nephropathy are major complications in patients with Type 2 diabetic nephropathy (T2DN); however, the role of renal damage on cardiac remodeling is not yet fully known. A retrospective research was conducted in 254 T2DN patients. All were divided into three groups according to urinary albumin excretion (UAE): the normoalbuminuria group (UAE < 30 mg/g, n = 18), the microalbuminuria group (UAE 30 - 300 mg/g, n = 99) and the macroalbuminuria group (UAE > 300 mg/g, n = 137). The parameters of cardiac remodeling, left atrial diameter (LAD), left ventricular diameter at the end of diastole (LVDd), interventricular septum (IVS), posterior wall of left ventricle (PWLV) and ejection fraction (EF), were determined by Doppler echocardiography. The effects of renal damage on cardiac remodeling were analyzed. Among the 254 patients, LAD and LVDd enlargement was found in 180 (70.86%) and 53 (20.86%) patients, respectively; 46 cases (18.11%) suffered from both LAD and LVDd enlargement. Compared with normal LAD/LVDd groups, creatinine clearance (Ccr) and hemoglobin (Hb) were significantly lower in the left atrial (LA) and left ventricular (LV) dilated groups. LAD was positively correlated with mesangial sclerosis, tubular-interstitial lesions, interstitial fibrosis, as well as tubular basement membrane thickness (r = 0.273, 0.208, 0.176, 0.155, p < 0.05, respectively). Moreover, in comparison to patients with LA enlargement, more severe renal damage was detected in patients with LV enlargement. There is a strong correlation between echocardiographic parameters and kidney lesions in patients with T2DN in China; the more severe the renal damage, the more severe the cardiac structural alteration. Renal damage contributes to cardiac remodeling, which may provide new insights into the pathogenesis of cardiovascular complications ,in diabetes mellitus.

Renal involvement in multiple myeloma

In this paper, the spectrum of renal involvement in the course of multiple myeloma (MM) is discussed. We describe the most important pathophysiological mechanisms underlying the development of renal complications observed in MM. In particular, we focused on the correlations between morphological changes in the kidneys and clinical signs and symptoms. Physicochemical characteristics of light chains that are synthesized in excess are critically important in the development of different types of renal involvement. It seems that patients with MM should be actively treated regardless of the type of lesions because the current methods allow to reverse renal lesions and reduce the negative effect of renal damage on prognosis in these patients.

Does renal ageing affect survival?

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Blunted erythropoietin response to anemia in patients with Type 1 diabetes.

It is known that patients with renal failure have normochromic normocytic anemia due to impaired endogenous erythropoietin (EPO) synthesis. The aim of this work was to determine whether low serum erythropoietin (s-EPO) levels play a role in the pathogenesis of anemia in patients with Type 1 diabetes without overt nephropathy. We included in the study 13 patients with Type 1 diabetes whose Hb levels were <11 g/dl. Blood cell count, s-EPO, urinary albumin excretion rate (AER), HbA(1c), glomerular filtration rate, serum iron, serum ferritin, the presence of neuropathy, retinopathy and nephropathy were determined. Ten out of 13 patients with anemia (77%) had a blunted EPO response to anemia. All ten patients with low EPO levels had autonomic neuropathy; five had clinical nephropathy but with serum creatinine<1.6 mg/dl. Three patients were treated with rHuEPO and showed an improvement in their anemia after treatment. The majority of patients with Type 1 diabetes who had anemia also had low EPO levels. The pathogenesis of this phenomenon is probably multifactorial. Autonomic neuropathy appears to play a role, but it is not sufficient, per se, to be the only cause. Dysautonomia might enhance the effect of renal damage.

Angionephrographic effect in renal damage: an experimental study in dogs.

Angionephrographic effect in renal damage: an experimental study in dogs.