Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective

Barnett, Lillie Marie A.; Cummings, Brian S.

doi:10.1093/toxsci/kfy159

Cited by 169 publications

(119 citation statements)

References 138 publications

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“…The process of nephrotoxicity usually encompasses changes in tubular cell toxicity, glomerular hemodynamics, crystal nephropathy, inflammation, thrombotic microangiopathy, and rhabdomyolysis. Diagnosis of nephrotoxicity is via measurement of serum creatinine, blood urea nitrogen (BUN), creatinine clearance, and glomerular filtration rate …”

Section: Resultsmentioning

confidence: 99%

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Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

et al. 2019

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Drug‐induced nephrotoxicity is a frequent serious adverse effect, contributing to morbidity and increased healthcare utilization. Prevention or reversal is key. Curcumin has useful biological features that include antioxidant, anti‐inflammatory, and anticancer properties. This review covers aspects of curcumin in relation to prevention of drug‐induced nephrotoxicity: dosage and schedule, effect on kidney biomarkers and histological changes, and mechanisms of curcumin's protective effects. Despite success in some animal models, human studies and clinical administration of curcumin for nephroprotection remains limited due to difficulty in achieving therapeutic levels following oral administration and in determining the optimal dosing schedule. Lack of sufficient evidence from animal studies, coupled with low systemic bioavailability, continues to limit the utilization of curcumin in addressing and controlling drug‐induced nephrotoxicity. Therefore, human studies are required to fully assess and validate the therapeutic potential of curcumin.

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Section: Resultsmentioning

confidence: 99%

“…Diagnosis of nephrotoxicity is via measurement of serum creatinine, blood urea nitrogen (BUN), creatinine clearance, and glomerular filtration rate. 75…”

Section: Kidney Function Histological Changes and Markers Of Oxidmentioning

confidence: 99%

Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

et al. 2019

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“…Nephrotoxicants, including chemotherapeutics, drugs of abuse, antimicrobials, radiocontrast agents, environmental pollutants, and natural substances, can induce kidney injury via similar mechanisms. Renal cell death can be mediated by drug transporters that determine the selectivity for the tubular cell, mitochondrial damage, and drug metabolism (Barnett and Cummings 2018). The reabsorption of solutes by the kidneys is a task that demands a large consumption of energy.…”

Section: Kidneys Can Experience Both Structural Damage and Loss Of Fumentioning

confidence: 99%

Kidney-based in vitro models for drug-induced toxicity testing

et al. 2019

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The kidney is frequently involved in adverse effects caused by exposure to foreign compounds, including drugs. An early prediction of those effects is crucial for allowing novel, safe drugs entering the market. Yet, in current pharmacotherapy, drug-induced nephrotoxicity accounts for up to 25% of the reported serious adverse effects, of which one-third is attributed to antimicrobials use. Adverse drug effects can be due to direct toxicity, for instance as a result of kidney-specific determinants, or indirectly by, e.g., vascular effects or crystals deposition. Currently used in vitro assays do not adequately predict in vivo observed effects, predominantly due to an inadequate preservation of the organs' microenvironment in the models applied. The kidney is highly complex, composed of a filter unit and a tubular segment, together containing over 20 different cell types. The tubular epithelium is highly polarized, and the maintenance of this polarity is critical for optimal functioning and response to environmental signals. Cell polarity is dependent on communication between cells, which includes paracrine and autocrine signals, as well as biomechanic and chemotactic processes. These processes all influence kidney cell proliferation, migration, and differentiation. For drug disposition studies, this microenvironment is essential for prediction of toxic responses. This review provides an overview of drug-induced injuries to the kidney, details on relevant and translational biomarkers, and advances in 3D cultures of human renal cells, including organoids and kidney-on-a-chip platforms.

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“…It leads to tubular cell damage and obstruction associated with interstitial inflammation, reno-microvascular contraction, and chronic intravascular volume depletion, in part caused by chronic dehydration and the effects of raised renin-angiotensin hormonal system [27,45], which exacerbates tubular oxidative stress [46]. CKDmfo is a fatal chronic tubulointerstitial disease in which renal tubules get blocked and inflamed in early stages [6,47]. With the gradual local spread of chronic inflammation and fibrosis, the entire kidney is affected [26,48].…”

Section: Ckdmfo: General Pathologymentioning

confidence: 99%

“…Most nongenetic renal tubulointerstitial diseases generally are attributed to exposure to chemical nephrotoxins [4,6,10,16], which can be acute (e.g., snake venom, drugs, toxins, infections, immunological reactions) or chronic, as in the case of CKDmfo. Chronic tubulointerstitial renal diseases can be caused by nephrotoxic substances, such as HMs, fluoride, or reflux nephropathy [47,[50][51][52][53][54].…”

Section: Toxic Tubular Nephropathymentioning

confidence: 99%

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

Wimalawansa¹,

Dissanayake

2019

Environments

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A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease. Research findings suggest that in addition to drinking water from stagnant sources that contain high ionic components, more than 10 years of exposure to environmental nephrotoxins and micronutrient malnutrition are needed to contract this fatal disease.

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Nephrotoxicity and Renal Pathophysiology: A Contemporary Perspective

Cited by 169 publications

References 138 publications

Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies

Kidney-based in vitro models for drug-induced toxicity testing

Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings

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