Chronic Kidney Disease Pathophysiology and Treatment Strategies

Chronic kidney disease (CKD) arises from a sustained decline in nephron number and function, leading to progressive loss of glomerular filtration, accumulation of metabolic waste and deranged electrolyte balance. Central to its pathophysiology are glomerulosclerosis and interstitial fibrosis, driven by persistent inflammation, oxidative stress and activation of the renin–angiotensin–aldosterone system. Endothelial injury, podocyte depletion and maladaptive repair mechanisms such as epithelial–mesenchymal transition converge to remodel the renal parenchyma. Systemic consequences include hypertension, anaemia and accelerated cardiovascular disease, which together impose a substantial global burden of morbidity and healthcare cost. Current treatments combine blood‐pressure control, tight glycaemic management and blockade of the renin–angiotensin–aldosterone system, supplemented by dietary modification and correction of mineral–bone disorder. Emerging strategies under investigation aim to retard fibrogenesis and inflammation by targeting novel signalling pathways, harnessing antioxidant therapies, modulating non-coding RNAs and exploring regenerative approaches such as cell therapy. Recent advances in sodium–glucose cotransporter-2 inhibition and precision medicine herald a shift towards multifaceted regimens that address both renal and extra-renal sequelae, offering real-world impact on quality of life and disease progression.

Research from Nature Portfolio

Recent studies have elucidated the role of C-reactive protein in promoting renal inflammation and fibrosis via a CD32b–Smad3–mTOR signalling axis, demonstrating that modulation of this pathway can attenuate proteinuria and structural damage in diabetic nephropathy models. In parallel, investigations into microRNA-212 overexpression in CKD have revealed its association with left ventricular hypertrophy and diastolic dysfunction, underscoring the heart–kidney interplay. These findings deepen understanding of cardiorenal crosstalk and open avenues for miRNA-based therapies that could concurrently protect renal function and mitigate cardiovascular risk.

Chronic Kidney Disease Pathophysiology and Treatment Strategies publication trend

The graph below shows the total number of articles in chronic kidney disease pathophysiology and treatment strategies across all publications each year (not limited to Nature Index journals).

Technical terms

Glomerulosclerosis: Scarring of the glomerular capillary network leading to reduced filtration.

Interstitial fibrosis: Deposition of extracellular matrix in the renal interstitium that impairs tissue architecture.

Renin–angiotensin–aldosterone system (RAAS): Hormonal cascade regulating blood pressure and fluid balance, often overactivated in CKD.

Oxidative stress: Imbalance between reactive oxygen species production and antioxidant defences causing cellular damage.

Epithelial–mesenchymal transition (EMT): Phenotypic switch of tubular cells to a fibrogenic state contributing to interstitial fibrosis.

MicroRNA: Small non-coding RNA molecules that regulate gene expression post-transcriptionally and influence disease pathways.

References

1. C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway. Scientific Reports (2016).
2. Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Scientific Reports (2019).
3. Intermedin protects peritubular capillaries by inhibiting eNOS uncoupling through AMPK/GTPCH-I/BH4 pathway and alleviate CKD following AKI. Free Radical Biology and Medicine (2025).
4. C-Phycoerythrin Prevents Chronic Kidney Disease-Induced Systemic Arterial Hypertension, Avoiding Oxidative Stress and Vascular Dysfunction in Remanent Functional Kidney. Marine Drugs (2024).
5. Mitochondrial Pathophysiology on Chronic Kidney Disease. International Journal of Molecular Sciences (2022).