CKD

• Proteinuria (albuminuria)

  Marker of kidney damage, higher levels increase risk of CKD progression & cardiovascular events, measured using urinalysis (uPCR, uACR preferred for CKD assessment)
• CKD management aims

  • Treat underlying conditions like hypertension and diabetes
  • Reduce risk of CKD progression with ACE inhibitors and SGLT-2 inhibitors
  • Reduce cardiovascular risk with lipid-lowering therapy
• CKD is expected to become the 5th leading cause of mortality by 2040 worldwide
• Blood pressure control targets are recommended for non-diabetics based on uACR levels
• Common Causes of CKD

  • Age
  • Diabetes
  • Hypertension
  • Glomerulonephritis (IgA, Lupus, Vasculitis)
  • Polycystic Kidney Disease (PKD)
  • Lower urinary tract disease (chronic pyelonephritis, reflux nephropathy, prostatic hyperplasia)
  • Medicines (NSAIDs, lithium, calcineurin inhibitors, methotrexate)
• Increasing age and the rising incidence of diabetes and hypertension are driving CKD cases
• Hypertension and CKD


  High blood pressure leads to scarred and narrowing of renal blood vessels, activation of Renin Aldosterone Angiotensin System (RAAS), and vasoconstriction
• KFRE (Kidney Failure Risk Equation) individualises a patient's risk of needing dialysis or a kidney transplant
• 1st line agent for blood pressure control is ACEi/ARB (Ramipril/Losa)
• Chronic Kidney Disease (CKD) is a progressive, irreversible decline in kidney function
• Chronic Kidney Disease (CKD) definition

  Reduction of eGFR to <60ml/min (at least 3 months) and/or markers of kidney damage present (proteinuria, haematuria, or structural abnormalities)
• Patients with CKD have an increased cardiovascular risk profile, including a higher risk of heart attack, stroke, and coronary artery disease
• 7.2 million people in the UK have CKD (>10%)
• eGFR


  A blood test estimating how well the kidneys are filtering (ml/min), as eGFR drops, kidney function decreases
• If 5-year risk is >5%, discussion with a kidney specialist is recommended
• Cardiovascular disease is the most common cause of death in patients with CKD
• 1st line agents for non-diabetic patients based on blood pressure targets

  • <30: ACEi/ARB (Ramipril/Losartan)
  • 30-70: ACEi/ARB (Ramipril/Losartan)
  • >70: ACEi/ARB (Ramipril/Losartan)
• Microalbuminuria is an early marker of kidney damage in DKD
• Statins should be offered to all patients with CKD regardless of cholesterol levels, with atorvastatin 20mg OD recommended by NICE Guidance
• Diabetes is the leading cause of end-stage renal disease
• The general HbA1c target is 7.0% (53mmol/mol) for DKD
• Finerenone, a novel MRA, is an add-on therapy in DKD, licensed in stage 3 and 4 diabetic CKD with albuminuria, reducing proteinuria, CKD progression, and risk of CV events
• RAAS inhibitors (ACEi/ARB) are renoprotective as they relieve pressure within the glomerulus by causing vasodilation of the efferent arteriole
• Cardiovascular disease is the most common cause of death in patients with Chronic Kidney Disease (CKD)
• Treatment regime for DKD should be individualised based on co-morbidities, but if uACR >3, it should include ACEi/ARB irrespective of blood pressure
• If diabetes is uncontrolled, it leads to altered haemodynamics, inflammation, and fibrosis in the kidney resulting in Diabetic Kidney Disease (DKD)
• SGLT-2 inhibitors inhibit sodium-glucose cotransporter 2 in the kidney, leading to reduced blood glucose levels and renoprotective effects
• SGLT-2 inhibitors have a renoprotective effect independent of blood glucose lowering, reducing CKD progression, proteinuria, and cardiovascular risk
• A large study comparing lipid-lowering therapy vs placebo in CKD patients showed a significant reduction in cardiovascular events in the treatment arm
• Mineral imbalance in CKD

  1. Healthy kidney activates Vit D absorbed from sun. Active Vit D increases calcium absorption from gut = Normal calcium level

  2. Kidney helps regulate phosphate level in the blood and eliminates any excess = Normal phosphate level

  3. Failing kidney cannot activate Vit D so calcium is no longer efficiently absorbed from gut = Low calcium level (Hypocalcemia)

  4. Kidney loses ability to eliminate excess phosphate. It accumulates in the blood = High phosphate (Hyperphosphatemia)
• Mineral and bone disorder - Vascular

  • Calcification leading to hardened arteries = heart and vessel disease
• Mineral and bone disorder: Symptoms

  • Early stages – no symptoms
  • Advanced mineral and bone disorder: Itching, Bone pain, Weak bones that break more easily, Calcification of blood vessels
• Mineral and bone disorder treatment needs to be combined with patient
• Mineral and bone disorder - Skeletal

  • Abnormal bone turnover, mineralisation & strength = weak painful bones (fracture risk)
• Disorder in CKD caused by mineral imbalance

  Skeletal and vascular problems
• Parathyroid hormone

  • Parathyroid glands maintain serum calcium levels
  • Parathyroid gland detects LOW CALCIUM, LOW VIT D and HIGH PHOSPHATE and releases a hormone parathyroid hormone (PTH)
• Mineral and bone disorder

  • Common complication of CKD
  • Affects 50-100% of people with CKD stages 3-5
  • Bone abnormalities are seen in almost all patients on dialysis
• Mineral and bone disorder involves

  • Vitamin D & Calcium
  • Phosphate
  • Parathyroid Hormone (PTH)
• Mineral and bone disorder: Diagnosis

  1. Blood tests: Calcium, phosphate, vit D and PTH

  2. A bone biopsy or a bone density X-ray (DEXA scan) may be needed

  3. Abdominal X-ray or an echocardiogram to assess if there is vascular involvement
• Mineral imbalance in CKD

  1. Healthy kidney PTH increases calcium and Vit D absorption, removes more phosphate = Normal calcium, phosphate, PTH gland switches off

  2. Failing kidney Low calcium and vit D levels trigger parathyroid gland to release more PTH = Low calcium, high phosphate, high PTH (PTH gland does not switch off). Hyperparathyroidism