Common pathophysiological mechanisms of chronic kidney disease: Therapeutic perspectives

Pathophysiological Mechanisms of Renal Fibrosis: A Review of Animal Models and Therapeutic Strategies

“…Diabetes and hypertension gradually lead to glomerular expansion, which causes endothelial dysfunction and haemodynamic changes: loss of the glomerular basement membrane electric charge and its thickening, a decreased number of podocytes, foot-process effacement and mesangial distension have been shown to underlie the initial glomerular injury, which probably leads to glomerulosclerosis. (1). The reaction of renal tissue to damage resembles the common wound-healing response that occurs in other tissues.…”

“…For the study of renal disease, this can be performed in one of two ways: a) unilateral nephrectomy plus polectomy of the remnant kidney, resulting in approximately 5/6 renal mass reduction; and b) unilateral nephrectomy plus complete ligation of two branches of the contralateral renal artery, resulting in infarction of approximately 2/3 of the remnant kidney, which produces an overall 5/6 renal mass nullification (1). In the 5/6 renal mass reduction model, the remaining nephrons increase their filtration rate (64) to preserve the excretory function; renal dysfunction occurs when the remaining nephrons are unable to perform this excretory function (1). Over time, these animals develop a syndrome of systemic and glomerular hypertension (68), proteinuria (64) and matrix expansion (5), and by 12 weeks present progressive glomerulosclerosis and tubulointerstitial fibrosis in the originally healthy remnant nephrons (23, 62, 68).…”

“…Urinary pathway obstruction, which may result either from the blockage of one or both ureters, provokes the progressive damage of renal structures, which leads to chronic renal dysfunction. Ureteral obstruction leads to kidney enlargement, caused by urine collecting in the renal pelvis or calyces, which causes hydronephrosis (1,71). This situation therefore causes renal dysfunction by impeding the normal flow of urine through the renal pelvis, ureters, bladder and urethra (1).…”

“…In developed countries, it is estimated that more than 10% of adults present some degree of CKD (1). Despite a varied initial evolution, which is related to the diversity of its aetiologies -namely genetics, autoimmune-related infections, environmental factors, diet, and drugs -progressive renal disease frequently results in renal fibrosis and finally in renal failure.…”

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients

“…CKD can result from a variety of ecologically distinct causes, including infectious glomerulonephritis, renal vascular, genetic alterations, autoimmune disease and oxidative stress. 9 Increased oxidative stress has been observed in CKD patients before the hemodialysis. 10 During the pathogenesis of CKD, ROS play important role in regulating the cell signaling pathways of nuclear factor kappa B (NF-iB), which can promote renal cell apoptosis and senescence and decrease regenerative ability of cells in the kidney.…”