Chronic kidney disease

Chronic Kidney Disease (CKD) is defined by the presence of either kidney damage or decreased kidney function for three months or more, irrespective of the cause. It is typically classified based on the estimated glomerular filtration rate (eGFR) and evidence of kidney damage, often measured by the level of proteinuria. It is typically progressive and may lead to end-stage renal disease (ESRD).

Here are the general criteria for CKD:

  • Kidney Damage:
    • Persistent abnormalities of kidney structure or function for more than three months identified by
      • Albuminuria
        • Typically assessed by the urine albumin-to-creatinine ratio (ACR)
      • Heamaturia (after exclusion of other cuases)
      • Renal imaging
      • Renal biopsy.
  • Decreased Kidney Function:
    • A normal eGFR > 60 mL/min/1.73 m²  with  evidence of kidney damage.
    • A reduced eGFR below 60 mL/min/1.73 m² with or without kidney damage.
    • CKD is categorized into five stages based on the eGFR:
      • Stage 1: Normal or high eGFR (≥90 mL/min/1.73 m²) with evidence of kidney damage.
      • Stage 2: Mildly decreased eGFR (60-89 mL/min/1.73 m²) with evidence of kidney damage.
      • Stage 3: Moderately decreased eGFR, subdivided into:
        • Stage 3a: eGFR 45-59 mL/min/1.73 m²
        • Stage 3b: eGFR 30-44 mL/min/1.73 m²
      • Stage 4: Severely decreased eGFR (15-29 mL/min/1.73 m²).
      • Stage 5: Kidney failure (eGFR <15 mL/min/1.73 m² or on dialysis).

Risk factors

Several risk factors can contribute to the development of CKD, including both modifiable and non-modifiable factors:

  • Non-modifiable risk factors:
    • Age: The risk of CKD increases as you age.
    • Family History: A family history of kidney disease can increase risk.
    • Ethnicity: Certain ethnic groups, such as ATSI, African American, Hispanic, Asian, or Native Americans, are at higher risk.
    • Genetics: Certain genetic conditions, like polycystic kidney disease, are linked to CKD.
    • Abnormal Kidney Structure: Conditions that affect the structure of the kidneys can lead to CKD.
  • Modifiable risk factors:
    • Diabetes: Diabetes is the leading cause of CKD. High blood sugar can damage blood vessels in the kidneys.
    • High Blood Pressure: Hypertension is the second leading cause of CKD. Uncontrolled blood pressure can cause damage to the blood vessels in the kidneys.
    • Cardiovascular Disease: Heart diseases increase the risk of CKD.
    • Obesity: Excess weight increases the risk of developing conditions like diabetes and hypertension, which in turn can lead to CKD.
    • Smoking: Smoking can damage kidney function and make existing kidney problems worse.
    • Recurrent Kidney Infection: Chronic urinary tract infections (UTIs) that reach the kidneys can cause scarring and lead to CKD.
    • Prolonged Use of Certain Medications: Long-term use of medications that can damage the kidneys, such as NSAIDs or certain antibiotics.
    • Toxic Exposure: Regular exposure to certain chemicals, such as lead or organic solvents, can increase the risk of kidney damage.
    • Glomerulonephritis: Inflammation of the kidney’s filtering units (glomeruli) can lead to CKD.
    • Interstitial Nephritis: Inflammation of the kidney’s tubules and surrounding structures.
    • Lupus and other autoimmune diseases: Conditions that cause inflammation throughout the body can also affect the kidneys.
    • Obstructive Uropathy: Chronic obstruction of the urinary tract, caused by conditions like kidney stones or enlarged prostate, can lead to CKD.
    • Repeated Episodes of Acute Kidney Injury: Kidney damage that occurs in short bursts but is severe can lead to CKD.

Diagnosis:

The diagnosis of CKD relies on blood tests, urine tests, imaging, and sometimes biopsy. Here are the steps to establish a diagnosis:

  • Assessment of Symptoms and Signs: Although many patients with early CKD are asymptomatic, symptoms such as fatigue, reduced urine output, pruritis, and edema can be indicative of CKD.
  • Blood Tests:
    • Full Blood Count (FBC) to look for anemia.
    • Creatinine and Electrolyte levels to assess kidney function.
    • Haematinics – Iron/B12/folate
    • Fasting Lipids
    • Fasting Glucose and/or HbA1c
    • Calcium, phosphate, parathyroid hormone (PTH), and Vitamin D
    • Autoimmune screen – CRP, ESR, ANA, ENA, Anti-glomerlar basement membrane
    • Vasculitis screen – ANCA, Complement
    • Serum electophoresis for myeloma
    • HIV, HBV, HCV, Syphilis serology
  • Urine Tests:
    • ACR
    • Haematuria and red cell casts
  • Imaging Tests:
    • Renal ultrasound to evaluate kidney size, structure, cysts, stones, obstruction.
    • Doppler ultrasound for renal artery stenosis
    • CT scans or MRI may be required for more detailed imaging.
  • Kidney Biopsy:
    • In selected cases where the cause of CKD is unclear or when specific glomerular diseases are suspected.

Differential Diagnosis:

When diagnosing CKD, it’s important to differentiate it from acute kidney injury (AKI), which is often reversible. Other conditions to consider include:

  • Diabetic nephropathy
  • Hypertensive nephrosclerosis
  • Glomerulonephritis
  • Polycystic kidney disease
  • Obstructive uropathies
  • Renal artery stenosis
  • Other systemic illnesses that affect the kidneys, such as lupus

Management:

Management of CKD includes both treatments to slow the progression of kidney damage and interventions to address the complications of decreased kidney function:

  • Control of Underlying Conditions: Optimal management of diabetes and hypertension are critical for slowing the progression of CKD.
    • BP target 130/80 mmHg
    • ACR target 50% fall
    • HbA1c target <7.0 (6.5-7.5)
    • Hb target 100-115 g/L
    • Cease any nephrotoxic drugs
    • Adjust doses of other drugs to suit eGFR
  • Medications:
    • ACE inhibitor or ARB (need K <5.5 to start) – max tolerated dose
    • Other BP medications as required to reach target
      • Thiazide
      • Ca channel blocker
      • Beta blocker (cardio selective)
    • Statin if:
      • <50 and 5 year CVD risk 15%
      • >50 all
    • Ezetimibe (if age > 50 and eGFR < 60)
    • SGLT2
    • Iron supplements (Ferritin > 100, Sat > 20%)
    • Erythropoetin
    • Once commenced Feritin > 200, Sat 20-30%
  • Diet and Lifestyle: A diet low in sodium, potassium, and protein may be recommended. Smoking cessation and regular exercise are also advised.
  • Management of Complications: This can include treatment for anemia (often with erythropoietin or iron supplements), bone disease (with vitamin D and phosphate binders), and acidosis.
  • Monitoring for Cardiovascular Disease: CKD increases the risk of cardiovascular disease, so lipid management, blood pressure control, and lifestyle interventions are important.
    • Death due to CVD is 10x more likely than ESRD
  • Referral to Nephrologist: If eGFR < 30 or 25% fall in 1 year, resistant hypertension, macroalbuminuria and combined haematuria/albuminuria
  • Dialysis: In later stages, peritoneal or haemodialysis may be needed to remove waste products and excess fluid from the blood.
  • Kidney Transplant: A transplant may be considered for suitable candidates.
  • Education and Monitoring: Regular monitoring of kidney function and education about CKD are vital components of care.
  • Renal Supportive Care is a program offered by the Kidney Foundation

Follow-up:

Patients with CKD require close monitoring to track the progression of the disease and adjust treatment as needed. Frequency of follow-up visits depends on the stage of CKD, the rate of progression, and the presence of complications or comorbid conditions.

SGLT2

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications initially developed to treat type 2 diabetes mellitus. They work by preventing the kidneys from reabsorbing glucose back into the bloodstream, which results in the excretion of glucose through the urine, thereby lowering blood glucose levels.

  • Role in CKD: Recent studies have shown that SGLT2 inhibitors have protective effects on the kidneys, independent of their blood sugar-lowering effects. These drugs have been found to:
    • Reduce the progression of CKD.
    • Lower the risk of developing end-stage kidney disease.
    • Decrease the incidence of cardiovascular events, which are common in patients with CKD.
  • Mechanism of Renal Protection: SGLT2 inhibitors confer renal protection through several mechanisms:
    • Reducing hyperfiltration in the glomeruli, which can lead to reduced kidney damage.
    • Lowering systemic blood pressure, which contributes to the reduction of intraglomerular pressure.
    • Decreasing the workload on the kidneys by lowering blood glucose levels.
  • Evidence: Clinical trials, such as the CREDENCE and DAPA-CKD trials, have demonstrated the benefits of SGLT2 inhibitors in slowing the progression of CKD and reducing the risk of cardiovascular events in patients with type 2 diabetes and CKD.
  • Indications for CKD: Based on these findings, the use of SGLT2 inhibitors is now recommended in guidelines for the management of CKD in patients with type 2 diabetes. Additionally, there is increasing interest in using these drugs in the treatment of CKD in patients without diabetes, given their renal and cardiovascular benefits.
  • Safety and Monitoring: While SGLT2 inhibitors are generally safe, they are associated with some risks, such as urinary tract infections, dehydration, hypotension, and a rare risk of diabetic ketoacidosis, even with only mildly elevated blood sugar levels. Therefore, patients on SGLT2 inhibitors require monitoring for these potential side effects.

In summary, SGLT2 inhibitors have emerged as an important therapeutic option for patients with CKD, particularly for those with type 2 diabetes. Their role in the treatment of CKD in non-diabetic patients continues to be an area of active research.