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Pathophysiology Of Acute And Chronic Renal Failure Pdf

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Professional Reference articles are designed for health professionals to use. You may find the Acute Kidney Injury article more useful, or one of our other health articles. NICE has issued rapid update guidelines in relation to many of these.

Chronic Kidney Disease

Yu HT. Progression of Chronic Renal Failure. Arch Intern Med. The author has no relevant financial interest in this article. Chronic renal failure is characterized by a persistently abnormal glomerular filtration rate. The rate of progression varies substantially. Mediators of the process include abnormal glomerular hemodynamics, hypoxia, proteinuria, hypertension, and several vasoactive substances ie, cytokines and growth factors.

Several predisposing host factors may also contribute to the process. Treatments to delay progression are aimed at treating the primary disease and at strictly controlling the systemic blood pressure and proteinuria. The role of antihypertensive agents, statins, and use of other maneuvers such as protein restriction and novel approaches are also discussed herein. Chronic renal failure is characterized by a persistently abnormal glomerular filtration rate GFR.

It represents an evolving process that is initiated by various causes, all with the common end result of persistent and usually progressive damage of varying severity to the kidneys. However, the rate of decline, often referred to as progression, can vary substantially.

The present article will discuss processes that affect progression after the initial renal insult has occurred. Chronic renal failure is a common problem. Many features are common to progression of renal failure of various causes, and the final histologic appearance is one of glomerulosclerosis, interstitial fibrosis, and loss of native renal cells. Nevertheless, the causes of chronic renal failure are heterogeneous, and the mechanisms and locations of the initial injury may vary.

Different animal models emphasize different aspects of the pathophysiologic characteristics and only incompletely replicate clinical disease. These represent the end result of the constant interplay between vasoactive substances ie, cytokines and growth factors. Impairment of renal function correlates better with the extent of tubulointerstitial injury than with histologic glomerular injury. The abnormal ECM contains an excess of normal components such as fibronectin, laminin, proteoglycans, and type IV collagen.

Apart from the evident histologic changes, alterations in the ECM composition also change the ways the cells interact with the ECM, and these in turn affect gene regulation in response to specific growth factors. The details remain an active area of inquiry. Myofibroblasts cells containing features of smooth muscle cells and of fibroblasts are involved in the fibrogenic process and can secrete alpha 2 I and alpha 2 III collagens and fibronectin.

Their origins vary because several types of intrarenal cells can transdifferentiate into myofibroblasts. Physiologic cell death is a normal event in tissue homeostasis and is important for removal of unnecessary or damaged cells.

In the context of renal disease, the balance between cell proliferation and apoptosis plays a critical role in maintaining an optimal number of cells after an insult. Because the normal ECM becomes replaced by an abnormal one, its antiapoptotic effect is lost.

The Fas apoptosis pathway is initiated by the binding of FasL to Fas, which triggers a cascade of intracellular signals that results in apoptotic deletion of Fas-bearing target cells. As a response to injury, overexpression of macrophage-colony stimulating factor by the tubules drives local macrophage proliferation in the kidney.

For purposes of the present discussion, mediators are factors and processes that perpetuate renal dysfunction after an initial insult of sufficient severity has occurred. They usually occur as a consequence, no matter how remote, of the initial renal damage Figure 1.

In rats subjected to subtotal nephrectomy, compensatory hyperfiltration of the spared nephrons helps to maintain overall GFR. However, this adaptation also leads to glomerular hypertension, proteinuria, and progressive chronic renal failure. Early diabetic nephropathy is well known to be associated with an elevated GFR. Thus, as in the remnant kidney model, the glomerular hypertension in diabetic nephropathy itself propagates chronic GFR decline, at least partly by increasing protein leakage across the glomerular capillaries into the Bowman space.

Hyperfiltration has not been well studied in nondiabetic human renal disease, and the extent to which this occurs in humans is not known for certain.

Keller et al 44 recently found that white hypertensive patients have fewer but larger glomeruli, suggesting compensatory hyperfiltration.

Modeling of human lupus nephritis also suggests that hyperfiltration occurs and is indeed beneficial, at least in the short term. Hypoxia has been regarded as a potential cause as well as effect of progression. There is loss of the postglomerular intertubular capillaries in chronic renal failure of various causes.

Expansion of the interstitial space may also diminish capillary perfusion of the tubules. Experimentally, this is associated with increased expression of the antiangiogenic factor thrombospondin 1 and decreased expression of the proangiogenic factor VEGF, which may impair angiogenesis and further propagate the hypoxia.

Cellular hypoxia prevents degradation of the transcription factor hypoxia-inducible factor 1, which then becomes available to bind to hypoxia-response elements in genes that are switched on by hypoxia. Proteinuria occurs as a result of glomerular capillary hypertension and damage to the permeability barrier in the glomerulus. Protein leaking across the glomerulus is taken up by the proximal tubule cells by endocytosis.

This causes protein overload on the proximal tubular cells, leading to increased activation of the intrarenal angiotensin-converting enzyme ACE 54 and also, either directly or via activation of transcription factors, 55 to abnormal production of the following cytokines: ET-1, monocyte chemoattractant protein 1, and RANTES regulated on activation, normal T-cell expressed and secreted.

These then interact with receptors located at the apical membrane of tubular cells to promote interstitial fibrosis. Specific protein metabolites may also be involved in the progression of chronic renal failure. In the presence of impaired glomerular permeability, transferrin in association with iron also enters the tubular lumen and is taken up by the proximal tubule cells.

Such accumulation has been demonstrated in human chronic renal disease. Consistent with its role in pathophysiology, proteinuria is a strong predictor of clinical progression of renal disease. The rapidity of GFR decline is proportional to the severity of proteinuria.

Systemic hypertension is a frequent accompaniment to chronic renal disease. Sodium, volume excess, and activation of the renin-angiotensin-aldosterone system in patients with chronic renal failure all cause hypertension. In addition, afferent stimuli from the kidneys may activate the sympathetic nervous system and contribute to the elevated pressure. There is at least 1 animal model in which proteinuria is ameliorated by inhibition of complements.

The kidneys contain all the machinery necessary to generate AII locally. Apart from its hemodynamic effects, AII also stimulates expression of fibronectin 80 and several other downstream cytokines and growth factors that favor fibrogenesis and recruitment of macrophages. As noted above, a growing list of vasoactive substances ie, cytokines and growth factors have been shown to be involved in progression of renal disease 84 - 95 Table 1. Cytokines and growth factors gain access to the kidneys by multiple pathways.

They can be synthesized elsewhere and be ultrafiltered across the glomeruli and act on tubular cells through apical receptors. Moreover, chemical mediators probably do not act in isolation; they often mediate the expression or release, or modulate the effect, of other mediators. There is also no universal agreement on the overexpression and underexpression of all cytokines among different models of renal disease studied by various investigators.

It is produced by resident renal cells and by infiltrating monocytes. Production is stimulated by various chemical stimuli such as AII, elevated plasma glucose, and IL-1, 13 as well as by mechanical stretching of mesangial and renal tubular cells.

Plasminogen Activator Inhibitor 1. There are 2 major systems involved in degradation of ECM: the plasminogen system and the matrix metalloproteinases. Both systems are activated by tissue-type plasminogen activator. Not detectable in the normal kidney, PAI-1 is expressed in the chronically damaged kidney and inhibits the ability of tissue-type plasminogen activator to convert plasminogen to plasmin and tissue matrix metalloproteinases to the active form.

In addition, PAI-1 may also inhibit the endothelial isoform of nitric oxide synthase and thereby locally decrease nitric oxide production. Loss of this inhibition, mediated either by cytokines or by loss or change of the normal matrix, favors ECM deposition. Nitric Oxide. Nitric oxide is formed by the oxidation of L-arginine into L-citrulline. Three isoforms of the nitric oxide synthase catalyze this reaction: constitutive endothelial nitric oxide synthase, neuronal nitric oxide synthase, and inducible nitric oxide synthase.

Nitric oxide inhibits mesangial cell proliferation and ECM synthesis and may limit capillary permeability. In rat models, nitric oxide inhibition results in proteinuria, 79 , increased blood pressure, and decreased GFR independent of renal AII levels.

A polymorphism of the endothelial nitric oxide synthase gene has been described and found to be associated with development of diabetic nephropathy, suggesting that the associated lower mean plasma nitric oxide level may translate into decreased suppression of ECM synthesis. Total nitric oxide production has been shown to be low in chronic renal failure in most, but not all, studies.

The major source of endogenous arginine is normally the proximal tubules. Whole-body L-arginine synthesis of arginine remains normal in hemodialysis patients and may reflect compensatory extrarenal synthesis. The extent to which local arginine availability may affect nitric oxide production locally is unclear. Parathyroid hormone, which is elevated in chronic renal failure, down-regulates nitric oxide synthase expression.

In patients with diabetes, scavenging of formed nitric oxide by advanced glycosylation end products may also contribute to the decreased nitric oxide levels. On the other hand, cytokines activated by injury may inappropriately activate inducible nitric oxide synthase. Aldosterone levels are often elevated in normokalemic patients with chronic renal failure.

Arterial hypertension, proteinuria, and glomerulosclerosis develop; these are ameliorated by the combination of an angiotensin receptor blocker ARB and an ACE inhibitor. Infusion of exogenous aldosterone restores the deleterious effects of subtotal nephrectomy, despite the concomitant administration of the ARB and the ACE inhibitor.

Aldosterone has also been shown to up-regulate ACE messenger RNA expression in cultured neonatal rat cardiocytes, thus completing a positive feedback mechanism. The ET system consists of 2 receptors, 3 ligands, and 2 activating peptidases. All are constitutively synthesized and released by glomerular and tubular cells. Several actions mediated by ET may play a role in the progression of renal failure: blockage of inducible nitric oxide synthase transcription via the ET A receptor; increased expression of the collagen 1 gene 81 ; vascular remodeling ; mediation of proteinuria ; macrophage chemotaxis; and stimulation of interstitial fibroblast proliferation and ECM synthesis.

This suggests that ETs play a role in at least some animal models. Platelet-derived growth factor has been implicated in the progression of renal injury. It stimulates mesangial proliferation and increases ECM synthesis.

Furthermore, overexpression of this cytokine, as well as its receptor, in the glomeruli and tubular and interstitial compartments has been demonstrated experimentally. Numerous host factors have been associated with progression of renal failure.

The most important ones are discussed below. A —base-pair fragment in intron 16 in the ACE gene can either be present the I allele or absent the D allele.

Progression of Chronic Renal Failure

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Acute kidney injury AKI in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine — the most common marker of AKI — should be identified. En consecuencia, las LRA ocasionan una importante carga para el sistema sanitario. However, it has not been until recently that intensivists have shown a growing interest in and awareness of its real impact on costs and outcomes, as evidenced by the dramatic increase in the number of articles published on this topic in dedicated journals Fig. At present, it is widely accepted that AKI is a common clinical syndrome in ICUs 1—3 and has a central role as a systemic disease causing multiple systemic sequels and lesions in extra-renal organs.

Acute on Chronic Kidney Failure, Acute on Chronic Kidney Injury

Acute kidney injury AKI is a common disorder, with a population incidence of about 2, per million population pmp. If the underlying cause of the acute component of ACRF can be ascertained, it should be treated promptly. If the sequelae of ACRF cannot be managed medically, prompt consideration of renal replacement therapy should be done. In patients without severe volume overload, acidemia can be treated with intravenous sodium bicarbonate.

Histopathology of chronic kidney disease of unknown etiology in Salvadoran agricultural communities. I Anatomical patho-logist with a master's degree in atherosclerosis. Associate professor, Nephrology Institute, Havana, Cuba. Corresponding author: laura. OBJECTIVE: Characterize histopathology of chronic kidney disease of unknown etiology in patients from Salvadoran agricultural communities, describe renal damage associated with each disease stage, and assess associations between histopathological alterations and sociodemographic variables.

A more recent article on acute kidney injury is available. Abstract Definition Etiology Clinical Presentation Diagnosis Management Prognosis Prevention References Article Sections Abstract Definition Etiology Clinical Presentation Diagnosis Management Prognosis Prevention References Acute kidney injury is characterized by abrupt deterioration in kidney function, manifested by an increase in serum creatinine level with or without reduced urine output. The spectrum of injury ranges from mild to advanced, sometimes requiring renal replacement therapy. The diagnostic evaluation can be used to classify acute kidney injury as prerenal, intrinsic renal, or postrenal.

Chronic Kidney Disease

Chronic kidney disease CKD is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies, and seizures. Diagnosis is based on laboratory testing of renal function, sometimes followed by renal biopsy. Treatment is primarily directed at the underlying condition but includes fluid and electrolyte management, blood pressure control, treatment of anemia, various types of dialysis, and kidney transplantation.

Yu HT. Progression of Chronic Renal Failure. Arch Intern Med. The author has no relevant financial interest in this article. Chronic renal failure is characterized by a persistently abnormal glomerular filtration rate. The rate of progression varies substantially. Mediators of the process include abnormal glomerular hemodynamics, hypoxia, proteinuria, hypertension, and several vasoactive substances ie, cytokines and growth factors.

NursingCenter Blog

Rahman M, Smith MC. Arch Intern Med. Chronic renal insufficiency ultimately culminating in end-stage renal disease requiring dialysis or transplantation is a major health problem in the United States.

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 - Он потянулся к клавиатуре.  - Мистер Беккер, пожалуйста, продиктуйте надпись. Медленно и отчетливо.


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Stephanie K. 21.03.2021 at 01:19

Patients with this pathology remain asymptomatic most of the time, presenting the complications typical of renal dysfunction only in more advanced stages.

Toussaint R. 23.03.2021 at 01:04

Chronic kidney disease CKD is long-standing, progressive deterioration of renal function.