Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection

Scholz, Holger; Boivin, Félix; Schmidt‐Ott, Kai M.; Bachmann, S.; Eckardt, Kai Uwe; Scholl, Ute I.; Persson, Pontus B.

doi:10.1038/s41581-021-00394-7

Cited by 171 publications

(173 citation statements)

References 164 publications

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“… 72 Further, the kidney’s unique vascularization leads to regional heterogeneity of oxygen supply and differential susceptibility to hypoxia. 61 Renal biopsies have demonstrated vascular changes, including cortical necrosis, tubular necrosis, and thrombotic microangiopathy in kidney tissue of patients with AKI, supporting a central role for vascular involvement in AKI. 66 An accumulation of uremic toxins is associated with endothelial damage and microvascular injury in AKI.…”

Section: What Is Known About the Etiology And Pathophysiology Of Severe Malaria-associated Aki?mentioning

confidence: 92%

“…Proximal tubular cells have a high metabolic rate and are susceptible to injury from ischemia or endogenous or exogenous toxins. 61 Endogenous nephrotoxins are a frequent etiological factor of AKI in children in sub-Saharan Africa. 62 Ultrastructural examination of kidney tissue of adults with fatal severe malaria reveals parasite sequestration in glomerular and tubulointerstitial vessels and monocyte accumulation in glomerular capillaries.…”

Section: What Is Known About the Etiology And Pathophysiology Of Severe Malaria-associated Aki?mentioning

confidence: 99%

“…Proximal tubular cells have a high metabolic rate and are susceptible to injury from ischemia or endogenous or exogenous toxins. 61 Following the loss of tubular cells from injury, epithelial cells can re-differentiate and replace lost or damaged cells as part of the natural repair process. 142 However, perturbations in the repair process can lead to fibrosis, or the development of CKD, placing survivors at risk for reduced lifespan and comorbidities, including cardiovascular disease, or kidney failure.…”

Section: Kidney Recovery Following Injurymentioning

confidence: 99%

See 2 more Smart Citations

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

Batte¹,

Berrens²,

Murphy³

et al. 2021

IJNRD

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Acute kidney injury (AKI) is emerging as a complication of increasing clinical importance associated with substantial morbidity and mortality in African children with severe malaria. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI, an estimated 24-59% of African children with severe malaria have AKI with most AKI community-acquired. AKI is a risk factor for mortality in pediatric severe malaria with a stepwise increase in mortality across AKI stages. AKI is also a risk factor for postdischarge mortality and is associated with increased long-term risk of neurocognitive impairment and behavioral problems in survivors. Following injury, the kidney undergoes a process of recovery and repair. AKI is an established risk factor for chronic kidney disease and hypertension in survivors and is associated with an increased risk of chronic kidney disease in severe malaria survivors. The magnitude of the risk and contribution of malaria-associated AKI to chronic kidney disease in malaria-endemic areas remains undetermined. Pathways associated with AKI pathogenesis in the context of pediatric severe malaria are not well understood, but there is emerging evidence that immune activation, endothelial dysfunction, and hemolysis-mediated oxidative stress all directly contribute to kidney injury. In this review, we outline the KDIGO bundle of care and highlight how this could be applied in the context of severe malaria to improve kidney perfusion, reduce AKI progression, and improve survival. With increased recognition that AKI in severe malaria is associated with substantial post-discharge morbidity and long-term risk of chronic kidney disease, there is a need to increase AKI recognition through enhanced access to creatinine-based and nextgeneration biomarker diagnostics. Long-term studies to assess severe malaria-associated AKI's impact on long-term health in malaria-endemic areas are urgently needed.

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Section: What Is Known About the Etiology And Pathophysiology Of Severe Malaria-associated Aki?mentioning

confidence: 92%

Section: What Is Known About the Etiology And Pathophysiology Of Severe Malaria-associated Aki?mentioning

confidence: 99%

Section: Kidney Recovery Following Injurymentioning

confidence: 99%

See 1 more Smart Citation

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

Batte¹,

Berrens²,

Murphy³

et al. 2021

IJNRD

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“…The most common causes of AKI, characterized by a sudden decrease in renal function, include ischemic insults, sepsis and poisoning, wherein hypoxia, pathogen- or damage-associated molecular patterns, inflammatory cytokines and environmental toxins or drugs damage the kidney, and particularly the tubular epithelium [ 251 , 252 , 253 ]. Its incidence is high (estimated to be 2–20% in hospitalized patients) and its mortality remains around 20% [ 251 ]. Of recent interest, AKI develops in 10% of hospitalized Covid-19 patients [ 254 ].…”

Section: Mrtf In Kidney Diseasesmentioning

confidence: 99%

MRTF: Basic Biology and Role in Kidney Disease

Miranda

Lichner

Szászi

et al. 2021

IJMS

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A lesser known but crucially important downstream effect of Rho family GTPases is the regulation of gene expression. This major role is mediated via the cytoskeleton, the organization of which dictates the nucleocytoplasmic shuttling of a set of transcription factors. Central among these is myocardin-related transcription factor (MRTF), which upon actin polymerization translocates to the nucleus and binds to its cognate partner, serum response factor (SRF). The MRTF/SRF complex then drives a large cohort of genes involved in cytoskeleton remodeling, contractility, extracellular matrix organization and many other processes. Accordingly, MRTF, activated by a variety of mechanical and chemical stimuli, affects a plethora of functions with physiological and pathological relevance. These include cell motility, development, metabolism and thus metastasis formation, inflammatory responses and—predominantly-organ fibrosis. The aim of this review is twofold: to provide an up-to-date summary about the basic biology and regulation of this versatile transcriptional coactivator; and to highlight its principal involvement in the pathobiology of kidney disease. Acting through both direct transcriptional and epigenetic mechanisms, MRTF plays a key (yet not fully appreciated) role in the induction of a profibrotic epithelial phenotype (PEP) as well as in fibroblast-myofibroblast transition, prime pathomechanisms in chronic kidney disease and renal fibrosis.

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“…It has been established that tubular dilatation, tubular epithelial damage, cast formation, and debris accumulation were all found in the renal medulla of ARF [9,26,27]. To confirm the effect of JGE administration on tubular injury, PAS staining analysis was performed.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Joa-Gui Em through the Improvement of the NLRP3 and TLR4/NF-κb Signaling by Ischemia/Reperfusion-Induced Acute Renal Failure Rats

Jang

Hong

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Joa-gui em (左歸飮, JGE) is known to be effective for treating kidney-yin deficient syndrome. However, there is a lack of objective pharmacological research on improving kidney function. This study was designed to evaluate whether JGE improves renal function and related mechanisms in rats with acute renal injury induced by ischemia/reperfusion (I/R). The acute renal failure (ARF) group was subjected to reperfusion after inserting a clip into the renal artery for 45 min. The ARF + JGE (100 or 200 mg/kg/day) groups were orally administered for four days after their I/R surgery, respectively. JGE treatment suppressed the increase in kidney size in the ARF animal model and alleviated the polyuria symptoms. In addition, to confirm the effect of improving the kidney function of JGE, lactate dehydrogenase levels, blood urea nitrogen/creatinine ratio, and creatinine clearance were measured. As a result, it decreased in the ARF group but significantly improved in the JGE group. Also, as a result of examining the morphological aspects of renal tissue, it was shown that JGE improved renal fibrosis caused by ARF. Meanwhile, it was confirmed that JGE reduced inflammation through the nucleotide-binding oligomerization domain-like receptor pyrin domain containing-3 (NLRP3) and toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathways, which are the major causes of acute ischemic kidney injury, thereby improving renal function disorder. The JGE has a protective effect by improving the NLRP3 and TLR4/NF-κB signaling pathway in rats with acute renal dysfunction induced by I/R injury.

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Kidney physiology and susceptibility to acute kidney injury: implications for renoprotection

Cited by 171 publications

References 164 publications

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

MRTF: Basic Biology and Role in Kidney Disease

Protective Effect of Joa-Gui Em through the Improvement of the NLRP3 and TLR4/NF-κb Signaling by Ischemia/Reperfusion-Induced Acute Renal Failure Rats

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