Kidney

Chronic Kidney Disease (CKD)

 
Contents
  1. About chronic kidney disease (CKD)
  2. Definition of CKD
  3. CKD risk factors
  4. Approved drug for CKD
  5. Endpoint for CKD
  6. Disease mouse model for CKD
  7. Reference Links

About chronic kidney disease (CKD)

Chronic kidney disease (CKD), a condition characterized by gradual structural and functional deterioration of the kidneys due to a variety of factors, has a significant impact on global health. Approximately 10-14% of the world’s adult population suffers from some form of chronic kidney disease, resulting in approximately 1.2 million deaths each year. By 2040, it’s predicted that chronic kidney disease will be the fifth leading cause of death worldwide, one of the largest increases of any major cause of death.

Definition of CKD

CKD is defined as abnormalities of kidney structure or function, present for > 3 months, with implications for health.

Criteria for CKD (either of the following present for > 3 months)

  1. Albuminuria (AER ≧ 30 mg/24 hours; ACR ≧30 mg/g [≧3 mg/mmol])
  2. Urine sediment abnormalities
  3. Electrolyte and other abnormalities due to tubular disorders
  4. Abnormalities detected by histology
  5. Structural abnormalities detected by imaging
  6. History of kidney transplantation

Decreased GFR

  1. GFR < 60 ml/min/1.73 m2 (GFR categories G3a–G5)

CKD risk factors

  1. Older age
  2. High blood pressure
  3. Diabetes
  4. Obesity
  5. Smoking
  6. Heart disease
  7. Acute kidney injury

Approved drug for CKD

  1. Jardiance (empagliflozin), Approved September 2023 for adults with chronic kidney disease
  2. Farxiga (dapagliflozin), Approved April of 2021 for adults with chronic kidney disease who are at risk of disease progression.
  3. Canagliflozin for diabetic kidney disease (), Approved September 2019

Endpoint for CKD

Endpoints assessed in previous approved drugs

empagliflozin 

  • Incidence rate of first occurrence of kidney disease progression (KDP)
  1. end stage kidney disease (defined as the initiation of maintenance dialysis or receipt of a kidney transplant) OR
  2. a sustained decline in estimated glomerular filtration rate (eGFR) to <10 mL/min/1.73m2 OR
  3. renal death OR
  4. a sustained decline of ≥40% in eGFR from randomisation.
  • Adjudicated cardiovascular death

dapagliflozin

  • Time to the First Occurrence of Any of the Components of the Composite: ≥50% Sustained Decline in eGFR or Reaching ESRD or CV Death or Renal Death
  • End Stage Renal Disease (ESRD) is defined as:
  1. Sustained eGFR <15 mL/min/1.73m2 or,
  2. Chronic dialysis treatment or,
  3. Receiving a renal transplant The proportional hazards Cox regression model takes into account the time to the event. Data is reported as the numbers of subjects with the event and the Hazard ratio is included in the Statistical Analysis section attached to the Outcome Measure data table.

Disease mouse model for CKD

UUO mouse model

  • The Unilateral Ureteral Obstruction (UUO) is a model widely used to study obstructive nephropathy and is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow.

ADR mouse model

  • Adriamycin (ADR)-induced nephropathy has been the leading model used to study human primary focal segmental glomerulosclerosis (FSGS), a common pathway for podocyte damage and glomerular loss of function that leads to kidney damage and failure. Commonly used both in rats and mice, the ADR model has been used to study the mechanisms that develop in FSGS and chronic kidney disease (CKD) as it allows for a spatio-temporal evaluation of pathophysiological events.

Adenine mouse model

  • The adenine-induced CKD animal model has gained attention due to its relative ease of implementation without surgery and encouraging outcomes. Orally administered adenine metabolizes to 2,8-dihydroxyadenine, which forms crystal in the proximal tubular epithelia leading to inflammation and subsequent tubulointerstitial fibrosis as well as anemia.

5/6 nephrectomy mouse model

  • 5/6 Nephrectomy (PNx) on rat and mouse mimics renal failure after loss of kidney function in human, and it has been widely used in CKD researches. The conventional 5/6 nephrectomy model removes one kidney and excises 2/3 of the other kidney 1 week later, which cause glomerular sclerosis and fibrosis.

Reference Links

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