Table 2.

The commonly used rodent models of CKD

CKD Models	Induction Methods	Models(Refs.)	Pathology	Pros and Cons
Interstitial fibrosis models	Surgical	UUO53,54	• Tubular injury and atrophy. • Myofibroblast activation and interstitial fibrosis. • Infiltration of inflammatory cells.	• Work in all species and strains. • Rapid and robust fibrosis. • No functional assessment. • Less clinically relevant.
		Severe UIRI23	• Tubular cell injury and atrophy. • Interstitial inflammation. • Long-term expression of tubular injury markers and cytokines.	• Avoid animal loss. • Significant fibrosis. • No functional assessment.
		Two-stage UIRI/UNX22	• Increased BUN and SCr levels. • Myofibroblast activation, interstitial fibrosis. • Interstitial inflammation.	• Avoid animal loss. • Significant fibrosis. • SCr and BUN assessing impaired compensation after UNX. • Additional surgery.
	Drug-induced	High-dose folic acid134	• Damage proximal tubular cells. • Interstitial inflammation. • Interstitial fibrosis, increased BUN and SCr.	• Modeling intratubular obstruction. • Moderate fibrosis.
		Repeated low-dose cisplatin34,58	• Tubular cell injury and atrophy. • Interstitial fibrosis, increased BUN and SCr. • Long-term expression of cytokines.	• Modeling clinical protocol. • Moderate fibrosis.
Remnant kidney model	Surgical	5/6 subtotal nephrectomy60,61	• Hypertension. • Proteinuria, glomerular sclerosis. • Tubulointerstitial inflammation and fibrosis.	• Recapitulate most human CKD features. • Work well in rats. • Resistant in C57BL6 mice.
Hypertensive nephropathy model	Drug-induced	DOCA-salt63	• Low-renin, neurogenic form of hypertension. • Renal sodium retention, aldosterone release, inflammation, and mild fibrosis. • Cardiovascular lesions.	• Neurogenic model of hypertension. • Relevant to humans.
		Ang II infusion62	• Hypertension, lesions in kidney, and extrarenal organs. • Proteinuria and mild-to-moderate podocyte injury. • Renal inflammation and mild fibrosis.	• Imitate systemic RAS activation. • Affects extrarenal organs such as heart.
	Genetic	Spontaneously hypertensive rat135,136	• Model of essential hypertension. • Mild proteinuria. • Renal inflammation and fibrosis. • Cardiovascular lesions.	• Spontaneity. • Enigmatic origin. • Normotensive WKY rats as controls.
Glomerular disease models	Drug-induced	Adriamycin65,67 Puromycin66,68	• Podocytes injury, proteinuria. • Glomerulosclerosis. • Tubular injury and interstitial fibrosis.	• Simple injection operation. • High reproducibility and relatively low mortality. • Resistant in C57BL6 mice.
	Immunological	Lupus nephritis (NZB/W F1, MRL/lpr, or BXSB strains)73	• Mesangial proliferation. • Proteinuria and glomerulonephritis. • Tubular atrophy and interstitial inflammation.	• Rodent sex-related. • Variable in individual animals.
		Thy-1 nephritis137	• Mesangial cell proliferation. • Inflammatory cell infiltration. • Mesangial matrix expansion. • Proteinuria and hematuria.	• Simple injection operation.
		Anti-GBM nephritis138,139	• Proteinuria and crescent formation. • Mesangial cell proliferation. • Inflammatory cell infiltration. • Interstitial fibrosis.	• Simple injection operation. • Variable susceptibility among different strains. • Animal loss.
Polycystic kidney disease models	Hereditary model	Pcy mice75,76 Cy rats PCK rats	• Renal cysts formation and grow. • Renal volume expansion. • Increased cell proliferation.	• Relatively long lifespan. • Suitable for pharmacological experiments. • Variable severity of phenotypes.
	Gene-modified model	Pkd1 knockout75,76	• Renal cysts formation and grow. • Renal volume expansion. • Increased cell proliferation. • Inflammatory cell infiltration. • Renal fibrosis.	• Relevant to humans. • Suitable for cystogenesis research.

UUO, unilateral ureteral obstruction; UIRI, unilateral ischemia–reperfusion injury; UNX, uninephrectomy; SCr, serum creatinine; DOCA, deoxycorticosterone acetate and high-salt; GBM, glomerular basement membrane. PCK, polycystic kidney; RAT, renin-angiotensin system; WKY, Wistar Kyoto.