Chronic kidney disease

• Chronic kidney disease is defined as a GFR of less than 60 ml/min for >90 days/3 months
• CKD can be causes by:

  • diabetes
  • hypertension
  • glomerularnephritis
  • cystic kidney disease (APCKD)
  • renovascular disease
• Many of the consequences of CKD start early, and include:

  • excretory/endocrine effects
  • dialysis/transplant/increased mortality and morbidity
• normal GFR is ∼125ml/min/1.73m2
• ways to test renal function:

  • creatinine clearance (24 hour urine collection, urea and creatinine together are more accurate)
  • isotope GRFs - expensive and time consuming
• serum creatinine can be very misleading as a way to test renal function, as it may be affected by age muscle mass/drugs, and urea
• after initial testing for renal function, a formulae must be used on the collected data, for estimated GFR (MDRD) or creatinine clearance (Cockcroft and gault) - based on creatinine
• there are 5 stages of CKD:

  • stage 1: normal (120-90 GFR)
  • stage 2: early CRF (90-60 GFR)
  • stage 3: moderate CRF (60-30 GFR)
  • stage 4: pre- ESRD (30-15 GFR)
  • stage 5: ESRD (15-0 GFR)
• strategies to prevent progression of CKD

  • control blood pressure (RAS inhibitor)
  • reduce proteinuria (RAS inhibitor)
  • if diabetes, optimise glycemic control through SGLT2 inhibitor (used for diabetes control but also have a positive affect on kidneys)
• SGLT2 inhibitor include:

  • Canagliflozin - renal outcome hazard ratio (HR) 0.7 / CV outcome HR 0.61
  • Dapagliflozin - renal outcome HR 0.56 / CV outcome HR 0.71
  • Emapagliflozin (still waiting for results)
• prognosis of CKD decreases the lower the GFR is (CKD stage), and the higher the protein urea is (>300 mg/g ; >30 mg/mmol)
• high protein in filterate (proteinuria) occurs due to diabetes or glomerular nephritis
• proteinuria causes the cells which reuptake proteins to become overloaded and “die”, which leads to formation of scaring and fibrosis
• ACE inhibitors cause efferent vasodilatation which reduces the glomerular pressure and reduces amount of protein urea
• if ACE inhibitors are not used for CKD, it can lead to chronic interstitial fibrosis of the nephron
• avoid potential toxins in CKD:

  • NSAID’s/ contrast/ Gentamicin
  • phosphate enemas
• many drugs need to be given at a lower dose in patients with CKD especially chemotherapy agents/antibiotics
• CKD complications can be sliplit into two groups, excretory and endocrine
• excretory complications of CKD include:

  • hypertension
  • hyperkalemia
  • acidosis
• endocrine complications of CKD include:

  • anaemia
  • renal osteoclystrophy
  • cardiovascular disease
  • malnutrition
• hypertension is common in CKD and end stage renal disease (ESRD), it can cause left ventricular hypertrophy/ stroke/ end-organ damage-eyes/ kidneys
• hyperkalaemia is common in CKD patients as GFR declines <25, but can also occur at GFR >25 due to diabetes and type 4 renal tubular acidosis, ACE inhibitors, high potassium diet
• hyperkalaemia in CKD is related to distal sodium delivery (↓DND with ↓GFR)
• for hyperkalaemia in CKD it is not advised to eat high potassium foods such as: orange juice, banana, crisps, nuts, beer/wine, baked potatoes, coffee, chips, chocolate, bean
• for hyperkalaemia in CKD, potassium binders can be given
• potassium binders include: patiromer/ sodium zirconium (taken orally with food to bind potassium in the gut)
• if patient has untreated hypertension (160/100) and CKD, the GFR can decrease by up to 12 ml/min/year, if hypertension is treated well and reduced to 130/80, the GFR can only reduce by 2 mo/min/year
• acidosis in chronic renal failure is due to animal protein food, inability to acidify urine in CKD and phosphate/sulphates/other anions are resorbed very late in the nephron
• the aim in acidosis caused by CKD is to keep serum bicarb>22 as it can of set the affects, thus treatment includes sodium bicarbonate (be careful of fluid overload)
• CKD generally causes normochromic normocytic anaemia, where the structure of the RBC is not affected, but the amount is
• CKD leads to a decreased responce of EPO to an hypoxic stimulus (kidneys), decreased red cell survival, iron deficiency, blood loss ( dialysis/blood samples/GI), and albumin/hyperPTH/B12+folate deficits
• for anaemia caused by CKD, erythropoietin (Epo) replacement therapy can be an option.
• Epo replacement therapy:

  • all patients with Hb<105 and adequate iron stores should be on Epo (better quality of life/ less dyspnoea/ reduced left ventricular hypertrophy)
  • target Hb is 100-120
  • if poor responce to Epo, check iron stores/ CRP/ B12+folate/ PTH/ aluminium/ malnutrition/ malignancy
• excessive Epo can cause hypertension/thrombosis, and so epo has to be reduced and patients are still a little anaemic
• renal osteoclystrophy is the umbrella term used to describe the bone condition in people with kidney disease
• renal osteoclystrophy can cause:

  • high turnover bone disease (secondary hyperparathyroidism)
  • low turnover bone disease (osteomalacia, a-dynamic bone disease, aluminium bone disease)
• mechanism of renal osteoclystrophy:

  • kidney damage leads to reduced Vitamin D production, which causes decreased plasma Ca
  • decreased Ca causes rickets in children and osteomalacia in adults (softening of bone)
  • the decreased Ca also causes increased PTH, which increases absorption of calcium phosphate from the GI and the bone, which can cause osteitis fibrosa
  • the PTH tries to causes increased Ca, but also ends up causing increased phosphate, which can build-up and causes hyperphosphatemia if kidneys are not working properly
• treatment of renal osteoclystrophy:

  • phosphate restriction (0.8-1g/kg/day), diet control Ca/non-Ca binders, and increases $Ca^{2+}$
  • vitamin D therapy (alfacalcidol) (increases Ca and decreases phosphate)
  • monitor PTH 6 monthly/yearly
  • parathyroidectomy may be required
• vessel classification:

  • intimal calcification (calcification of cholesterol plaques in the lumen of the vessel, seen in CVD)
  • medial calcification (due to high phosphate and Ca, calcification in the wall of the vessel)
• consequences of hyperphosphatemia:

  • damaged vessel
  • calciphylaxis (calcific uremic arteriolopathy)