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


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.


Chronic kidney disease Proteinuria Treatment 



Angiotensin converting enzyme


Atrial natriuretic peptide


Angiotensin receptor I blocker


Body mass index


Congenital anomalies of the kidney and urinary tract


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


Chemokine (C-C motif) ligand 5


β chemokine receptor


Chronic kidney disease


Chronic Kidney Disease in Children cohort


Connective tissue growth factor


Diabetic nephropathy


Extracellular matrix


End-stage kidney disease




Focal segmental sclerosis


Glomerular basement membrane


Glomerular filtration rate


3-Hydroxy-3-Methylglutaryl CoA


Interstitial fibrosis


Kidney Disease Outcomes Quality Initiative


Monocyte chemotactic protein 1 (CCL 2)


Matrix metalloproteinase


Mesenchymal stromal cell


Nicotinamide adenine dinucleotide phosphate


Neutral endopeptidase


Nitric oxide


Nitric oxide synthase


Puromycin aminonucleoside


Peroxisome-proliferator-activated-receptor γ


Peritubular epithelial cell


Renin angiotensin aldosterone system


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


Reactive oxygen species


Transforming growth factor β


Tumor necrosis factor α


Vitamin D receptor


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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