scholarly journals Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease

2020 ◽  
Vol 31 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Donald E. Wesson ◽  
Jerry M. Buysse ◽  
David A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Acid Excretion ◽  
Adaptive Responses ◽  
Disease Treatment ◽  
Chronic Metabolic Acidosis ◽  
Progression Of Kidney Disease

Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.

A4982 Effects of obesity on urinary acid excretion and kidney injury in chronic kidney disease

2018 ◽  
Vol 36 ◽  
pp. e40
Author(s):  
Yuichiro Izumi ◽  
Koji Eguchi ◽  
Yushi Nakayama ◽  
Naomi Matsuo ◽  
Akiko Hara ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Acid Excretion ◽  
Urinary Acid

Pathophysiology of Acute Kidney Injury, Repair, and Regeneration

2014 ◽  
Author(s):  
Ching-Wei Tsai ◽  
Sanjeev Noel ◽  
Hamid Rabb
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Critical Role ◽  
Recovery Period ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Phase Cell ◽  
M2 Macrophage ◽  
Renal Stem Cells

Acute kidney injury (AKI), regardless of its aetiology, can elicit persistent or permanent kidney tissue changes that are associated with progression to end-stage renal disease and a greater risk of chronic kidney disease (CKD). In other cases, AKI may result in complete repair and restoration of normal kidney function. The pathophysiological mechanisms of renal injury and repair include vascular, tubular, and inflammatory factors. The initial injury phase is characterized by rarefaction of peritubular vessels and engagement of the immune response via Toll-like receptor binding, activation of macrophages, dendritic cells, natural killer cells, and T and B lymphocytes. During the recovery phase, cell adhesion molecules as well as cytokines and chemokines may be instrumental by directing the migration, differentiation, and proliferation of renal epithelial cells; recent data also suggest a critical role of M2 macrophage and regulatory T cell in the recovery period. Other processes contributing to renal regeneration include renal stem cells and the expression of growth hormones and trophic factors. Subtle deviations in the normal repair process can lead to maladaptive fibrotic kidney disease. Further elucidation of these mechanisms will help discover new therapeutic interventions aimed at limiting the extent of AKI and halting its progression to CKD or ESRD.

scholarly journals Microvascular rarefaction and hypertension in the impaired recovery and progression of kidney disease following AKI in preexisting CKD states

2018 ◽  
Vol 315 (6) ◽  
pp. F1513-F1518 ◽  
Author(s):  
Aaron J. Polichnowski
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Injury ◽  
Major Complication ◽  
Progression Of Kidney Disease ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage ◽  
Progression Of Renal Disease ◽  
Microvascular Rarefaction

Acute kidney injury (AKI) is a major complication in hospitalized patients and is associated with elevated mortality rates. Numerous recent studies indicate that AKI also significantly increases the risk of chronic kidney disease (CKD), end-stage renal disease (ESRD), hypertension, cardiovascular disease, and mortality in those patients who survive AKI. Moreover, the risk of ESRD and mortality after AKI is substantially higher in patients with preexisting CKD. However, the underlying mechanisms by which AKI and CKD interact to promote ESRD remain poorly understood. The recently developed models that superimpose AKI on rodents with preexisting CKD have provided new insights into the pathogenic mechanisms mediating the deleterious interactions between AKI and CKD. These studies show that preexisting CKD impairs recovery from AKI and promotes the development of mechanisms of CKD progression. Specifically, preexisting CKD exacerbates microvascular rarefaction, failed tubular redifferentiation, disruption of cell cycle regulation, hypertension, and proteinuria after AKI. The purpose of this review is to discuss the potential mechanisms by which microvascular rarefaction and hypertension contribute to impaired recovery from AKI and the subsequent progression of renal disease in preexisting CKD states.

scholarly journals Risks of chronic metabolic acidosis in patients with chronic kidney disease

2005 ◽  
Vol 67 ◽  
pp. S21-S27 ◽  
Author(s):  
Joel D. Kopple ◽  
Kamyar Kalantar-Zadeh ◽  
Rajnish Mehrotra
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Chronic Metabolic Acidosis

scholarly journals Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That of Diabetes or Obesity

2017 ◽  
Vol 8 (1) ◽  
pp. 41-49 ◽  
Author(s):  
Adam Whaley-Connell ◽  
James R. Sowers
Keyword(s):  
Insulin Resistance ◽  
At Risk ◽  
Kidney Disease ◽  
Kidney Tissue ◽  
Tubuloglomerular Feedback ◽  
Central Component ◽  
Metabolic Dysregulation ◽  
Elevated Systolic Blood Pressure ◽  
Progression Of Kidney Disease

Insulin resistance is a central component of the metabolic dysregulation observed in obesity, which puts one at risk for the development of type 2 diabetes and complications related to diabetes such as chronic kidney disease. Insulin resistance and compensatory hyperinsulinemia place one at risk for other risk factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of kidney disease. Our traditional view of insulin actions focuses on insulin-sensitive tissues such as skeletal muscle, liver, adipose tissue, and the pancreas. However, insulin also has distinct actions in kidney tissue that regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways which, in turn, impact glomerular filtration, including that governed by tubuloglomerular feedback. However, it is often difficult to discern the distinct effects of excess circulating insulin and impaired insulin actions, as exist in the insulin resistance individual, from the associated effects of obesity or elevated systolic blood pressure on the development and progression of kidney disease over time. Therefore, we review the experimental and clinical evidence for the distinct impact of insulin resistance on kidney function and disease.

Angiotensin-(1–7) in kidney disease: a review of the controversies

2012 ◽  
Vol 123 (6) ◽  
pp. 333-346 ◽  
Author(s):  
Danielle Zimmerman ◽  
Kevin D. Burns
Keyword(s):  
Angiotensin Ii ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Biological Effects ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Biologically Active ◽  
Renal Vasculature ◽  
Experimental Conditions ◽  
Enzymatic Pathways

Ang-(1–7) [angiotensin-(1–7)] is a biologically active heptapeptide component of the RAS (renin–angiotensin system), and is generated in the kidney at relatively high levels, via enzymatic pathways that include ACE2 (angiotensin-converting enzyme 2). The biological effects of Ang-(1–7) in the kidney are primarily mediated by interaction with the G-protein-coupled receptor Mas. However, other complex effects have been described that may involve receptor–receptor interactions with AT1 (angiotensin II type 1) or AT2 (angiotensin II type 2) receptors, as well as nuclear receptor binding. In the renal vasculature, Ang-(1–7) has vasodilatory properties and it opposes growth-stimulatory signalling in tubular epithelial cells. In several kidney diseases, including hypertensive and diabetic nephropathy, glomerulonephritis, tubulointerstitial fibrosis, pre-eclampsia and acute kidney injury, a growing body of evidence supports a role for endogenous or exogenous Ang-(1–7) as an antagonist of signalling mediated by AT1 receptors and thereby as a protector against nephron injury. In certain experimental conditions, Ang-(1–7) appears to paradoxically exacerbate renal injury, suggesting that dose or route of administration, state of activation of the local RAS, cell-specific signalling or non-Mas receptor-mediated pathways may contribute to the deleterious responses. Although Ang-(1–7) has promise as a potential therapeutic agent in humans with kidney disease, further studies are required to delineate its signalling mechanisms in the kidney under physiological and pathophysiological conditions.

scholarly journals Energy turnover and the production of ammonium by the kidney: effect of hypernatremia

1992 ◽  
Vol 70 (1) ◽  
pp. 8-12
Author(s):  
Mitchell L. Halperin ◽  
Ching-Bun Chen
Keyword(s):  
Body Weight ◽  
Oxygen Consumption ◽  
Metabolic Acidosis ◽  
Metabolic Regulation ◽  
Urine Flow ◽  
Acid Excretion ◽  
Acid Base ◽  
Energy Turnover ◽  
Chronic Metabolic Acidosis ◽  
Rate Of Oxygen Consumption

The purpose of this study was to explore further the relation between the rates of oxygen consumption and ammonium (NH4+) production in the kidney during chronic metabolic acidosis. The experimental model was the dog with chronic metabolic acidosis because of the extensive background literature in this species. Chronic metabolic acidosis was produced by the ingestion of 10 mmol NH4Cl/kg body weight for 5 days. There was a significant increase in the rate of oxygen extraction when hypernatremia was present. Despite this rise in the rate of oxygen consumption, there was no increase in the rate of NH4+ production nor in the rate of glutamine extraction. These data suggest that hypernatremia might prevent a further augmentation in glutamine extraction when the rate of oxygen consumption rises. In addition, a larger proportion of the NH4+ produced was excreted in the urine during hypernatremia. This increase was associated with a rise in the urine flow rate, but not with a fall in urine pH.Key words: Acid–base, ATP, glutamine, energy metabolism, metabolic acidosis, metabolic regulation, net acid excretion, oxygen consumption.

Sign in / Sign up

Export Citation Format

Share Document