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Pediatric Nephrology

, Volume 29, Issue 5, pp 779–792 | Cite as

Chronic kidney disease: a new look at pathogenetic mechanisms and treatment options

  • Damien Noone
  • Christoph Licht
Review

Abstract

The concept of renoprotection has evolved significantly, driven by improved understanding of the pathophysiology of chronic kidney disease (CKD) and the advent of novel treatment options. Glomerular hyperfiltration, hypertension and proteinuria represent key mediators of CKD progression. It is increasingly recognized that proteinuria may actually be pathological and etiological in CKD progression and not just symptomatic. It initiates a sequence of events involving activation of proinflammatory and profibrotic signaling pathways in proximal tubular epithelial cells with transmission of the disease to the tubulointerstitium and progression to end-stage kidney disease (ESKD). Although the etiology and epidemiology of pediatric CKD differs to that in adults, studies in the various animal models of kidney disease, from obstructive uropathy to glomerulonephritis, have revealed that many common proinflammatory and profibrotic pathways are induced in progressive proteinuric CKD, irrespective of the primary disease. This pathomechanistic overlap therefore translates into the potential for common treatment targets for a wide spectrum of kidney diseases. In this review we therefore discuss the experimental and clinical evidence for an array of prospective future drug treatments of CKD progression. While conceptually promising, clear definitive evidence beyond preclinical data does not exist for many of these treatments, and others are limited by serious adverse effects. More studies are needed before general recommendations can be given.

Keywords

Chronic kidney disease Proteinuria Treatment 

Abbreviations

ACE

Angiotensin converting enzyme

ANP

Atrial natriuretic peptide

ARB

Angiotensin receptor I blocker

BMI

Body mass index

CAKUT

Congenital anomalies of the kidney and urinary tract

CCL 2

Chemokine (C-C motif) ligand 2 (MCP 1)

CCL 5/RANTES

Chemokine (C-C motif) ligand 5

CCR

β chemokine receptor

CKD

Chronic kidney disease

CKiD

Chronic Kidney Disease in Children cohort

CTGF

Connective tissue growth factor

DN

Diabetic nephropathy

ECM

Extracellular matrix

ESKD

End-stage kidney disease

ET

Endothelin

FSGS

Focal segmental sclerosis

GBM

Glomerular basement membrane

GFR

Glomerular filtration rate

HMG CoA

3-Hydroxy-3-Methylglutaryl CoA

IF

Interstitial fibrosis

KDOQI

Kidney Disease Outcomes Quality Initiative

MCP 1

Monocyte chemotactic protein 1 (CCL 2)

MMP

Matrix metalloproteinase

MSC

Mesenchymal stromal cell

NADPH

Nicotinamide adenine dinucleotide phosphate

NEP

Neutral endopeptidase

NO

Nitric oxide

NOS

Nitric oxide synthase

PAN

Puromycin aminonucleoside

PPAR γ

Peroxisome-proliferator-activated-receptor γ

PTEC

Peritubular epithelial cell

RAAS

Renin angiotensin aldosterone system

RANTES

Regulated upon activation normal T-cell expressed, and secreted (CCL 5)

ROS

Reactive oxygen species

TGF β

Transforming growth factor β

TNF α

Tumor necrosis factor α

VDR

Vitamin D receptor

VEGF

Vascular endothelial growth factor

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Copyright information

© IPNA 2013

Authors and Affiliations

  1. 1.Division of Nephrology, Department of PaediatricsThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Program in Cell BiologyThe Hospital for Sick ChildrenTorontoCanada
  3. 3.Department of PaediatricsUniversity of TorontoTorontoCanada

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