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Hydrogen Sulfide and the Kidney

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Advances in Hydrogen Sulfide Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1315))

Abstract

Hydrogen sulfide (H2S) is constitutively synthesized in the kidney. Recent investigations suggest a role for H2S in the regulation of fundamental kidney physiological events including arterial blood flow, glomerular filtration, and electrolyte and water transport. Deficiency of H2S generation has been implicated in acute kidney injury brought on by ischemia, administration of nephrotoxic medications, and obstruction. A role for impaired H2S expression has been shown in chronic kidney injury seen with chronic heart failure, obesity, and diabetes. Deficient H2S generation by the kidney could contribute to blood pressure dysregulation in models of hypertension and preeclampsia. Aging induced chronic kidney impairment is associated with inadequate H2S generation in the kidney. The mechanistic pathways regulated by H2S include but not limited to transcription, mRNA translation, signaling, inflammation, and oxidative stress demonstrating the versatility of the gasotransmitter. In the aforementioned conditions amelioration of kidney injury has been reported by the administration of agents that provide H2S. In renal cancer H2S may participate as an injurious agent. Overall, research on H2S in the kidney is in its early stages, and it is becoming evident that it has a context-dependent nuanced role in various kidney pathologies. There is an urgent need for exploration of H2S in physiology and pathology of the kidney including its role in oxygen sensing and glomerulonephritis. H2S may prove to be a novel therapeutic agent in some kidney disease states.

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Abbreviations

3-MST:

3-mercaptopyruvate sulfurtransferase

AAT:

Aspartate amino transferase

ACC:

Acetyl-CoA carboxylase

AE1:

Anion exchanger-1

AKI:

Acute kidney injury

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

AQP2:

Aquaporin-2

AT1:

Angiotensin receptor type 1

ATP:

Adenosine triphosphate

ATPase:

Adenosine triphosphatase

Bnip3:

BCL2/adenovirus E1B 19kDA-interacting protein

CBS:

Cystathionine β-synthase

ccRCC:

Clear cell renal cell carcinoma

cGMP:

Cyclic guanosine monophosphate

CHF:

Congestive heart failure

CKD:

Chronic kidney disease

CO:

Carbon monoxide

CSE:

Cystathionine γ-lyase

DAO:

D-amino acid oxidase

DKD:

Diabetic kidney disease

EGF:

Epidermal growth factor

EMT:

Epithelial-mesenchymal transition

ENaC:

Epithelial Na channel

eNOS:

Endothelial NO synthase

ER:

Dietary restriction

ERK:

Extracellular-signal-regulated kinase

ESKD:

End stage kidney disease

FGF23:

Fibroblast growth factor 23

FOXO3:

Forkhead box O3

GFR:

Glomerular filtration rate

GSK-3β:

Glycogen synthase kinase-3β

H2S:

Hydrogen sulfide

HIF:

Hypoxia inducible factor

HO-2:

Hemoxygenase-2

HS:

Hydrosulfide

IGF1:

Insulin-like growth factor 1

IL:

Interleukin

iNOS:

Inducible NO synthase

IRI:

Ischemic renal injury

IRβ:

Insulin receptor β

JNK:

c-Jun N-terminal kinase

KIM-1:

Kidney injury molecule-1

MAP kinase:

Mitogen-activated protein kinase

miR:

microrna

MMP:

Matrix metalloprotease

mTORC1:

Mechanistic target of rapamycin complex 1

NAD:

Nicotinamide adenine dinucleotide

NaHS:

Sodium hydrosulfide

NFκB:

Nuclear factor κ B

NMDA:

N-methyl D-aspartate

NO:

Nitric oxide

NOX:

NADPH (nicotinamide adenine dinucleotide phosphate) oxidase

Nrf-2:

Nuclear factor erythroid-2 related factor-2

PARP-1:

Poly(ADP ribose) polymerase-1

PI 3 kinase:

Phosphoinositide 3 kinase

PKG-II:

cGMP activated protein kinase G-II

PlGF:

Placental growth factor

PTEN:

Phosphatase and tensin homolog

RCC:

Renal cell carcinoma

ROS:

Reactive oxygen species

SASP:

Senescence associated secretory phenotype

sFlt1:

Soluble fms-like tyrosine kinase

sGC:

Soluble guanylyl cyclase

Sirt:

Sirtuin

TGFβ:

Transforming growth factor β

TNFα:

Tumor necrosis factor α

VEGF:

Vascular endothelial growth factor

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Acknowledgement

The author wishes to thank high school and college students, physicians-in-training, post-doctoral fellows, and collaborators without whose contributions work done in his laboratory and cited in this article would not have been possible. He also gratefully acknowledges funding support from the NIH, Veterans Research Administration Service, National Kidney Foundation, American Diabetes Association, and the Juvenile Diabetes Research Foundation over the years.

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Authors and Affiliations

  1. Center for Renal Precision Medicine, Department of Medicine, University of Texas Health, San Antonio, TX, USA

    Balakuntalam S. Kasinath & Hak Joo Lee

  2. Barshop Institute for Longevity and Aging Studies, University of Texas Health, San Antonio, TX, USA

    Balakuntalam S. Kasinath

  3. Geriatric Research, Education & Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA

    Balakuntalam S. Kasinath

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  1. Balakuntalam S. Kasinath
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  2. Hak Joo Lee
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Correspondence to Balakuntalam S. Kasinath .

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  1. Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Shanghai, China

    Yi-Chun Zhu

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Kasinath, B.S., Lee, H.J. (2021). Hydrogen Sulfide and the Kidney. In: Zhu, YC. (eds) Advances in Hydrogen Sulfide Biology. Advances in Experimental Medicine and Biology, vol 1315. Springer, Singapore. https://doi.org/10.1007/978-981-16-0991-6_2

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