Chronic Kidney Disease (CKD)

Question 1

Define CKD

Answer 1

• Kidney damage or a GFR <60 lasting for 3 months or more, regardless of the cause
• Or, significant proteinuria

Question 2

End Stage Renal Disease (ESRD)

Answer 2

• Chronic kidney failure treated with dialysis or transplantation

Question 3

CKD risk scale

Answer 3

Question 4

Types of CKD

Answer 4

1. Community CKD- disease of elderly patients with comorbidities. Associated with a reduced and very slow age releated decline in GFR, with most patients dying before reaching ESRD.
   
   • After age 40-50 there is a natural decline in GFR of ~.75 per year. However, certain risk factors make one more likely to have CKD (hypertension, diabetes, atherosclerosis).
2. Referred CKD - patients have significant nephorpathies causng early renal impairment and progress to ESDR
   
   • Patients often present at an earlier age due to either an acquried hereditary nephropathy (i.e., polycystic kidney disease) or an acquried nephropahty (i.e., diabetic nephropathy), that results in progressive damage and loss of function.

Question 5

Risk factors of CKD

Answer 5

• Age
• Race/ethnicity (non-caucasion)
• Genetics
• Low birth weight
• Systemic hypertension
• Diabetes mellitus
• Cardiovascular disease
• Albuminuria
• Obesity or metabolic syndrome
• Dyslipidemia
• Hyperuricemia
• Smoking
• Low SES
• Nephrotoxin exposure - NSAIDs, analgesics, heavy metals

Question 6

Explain the role of hypertension in CKD development

Answer 6

• Hypertension is a major cause of ESRD. It is due to the transmission of systemic hypertension into glomerular capillary beds resulting in glomerular hypertension and contributes to the progression to glomerulosclerosis

Question 7

CKD progression

Answer 7

• Chronic and sustained injury to the kidney, as seen in CKD, evolves to progressive kidney fibrosis with destruction of normal microarchitecture of the kidney being replaced by fibrous tissue (made of collagen), resulting in a loss of function.
  
  • Damages all components of the kidney (glomerular, tubules, interstitum, vasculature)

Question 8

CKD Pathophysiology

Answer 8

Question 9

Endothelial cell damage in CKD

Answer 9

• Damage to glomerular endothelial cells can be triggered by an acute inflammatory process, metabolic insult (diabetes), or hemodynamic shear stress (hypertension).
• Usually the endothelium has protective functions (anticoagulant, anti-inflammatory, and antiproliferative). Damage to endothelium alters the layers so it becomes proaggreggatory, proinflammatory, and mitogenic, resulting in a accumulation of inflammatory cells and platelets.
• Overall, we see stimulation and proliferation of mesangial cells

Question 10

Podocytes cell damage CKD

Answer 10

• Podocytes are very specialized epithelial cells with little ability to proliferate.
• The foot processes of the podoctyes are very important to the filtration barrier. A podoctyes loss of >40% results in segmental sclerosis and progressive CKD.
• Podocytes are a target in a variety of glomerular disease and can be effected by mutation and various circualtion factors

Question 11

Tubular cell damage in CKD

Answer 11

• As tubular cells are damaged they attempt to repair themselves - surviving cells dedifferentiated into embroyonic penotypes that allows them to repopulate the tubules. However, repeated injury will result in tubular cells transforming into myofibroblasts.

Question 12

Vascular cell damage in CKD

Answer 12

• Vascular sclerosis is a feature of renal scarring. Renal arteriolar hyalinosis is seen at early stages of CKD, even without hypertension.
• Changes in postglomerular arterioles and peritubular capillaries may worsen interstitial ischemia and fibrosis.
• Ischemia stimulates tubular cells and kidney fibrosis to produce ECM, resulting in accumulation of ECM.

Question 13

Clinical Presentation CKD

Answer 13

• CKD is generally asymptomatic until stage 4 or 5. It is generally detecte via routine blood testing.
• Early diagnosis with management may slow progression and reduce risk of CVD.

Question 14

Investigations CKD

Answer 14

• GFR - if distinction between AKI and CKD is unclear, GFR should be re-measured 2 weeks after intital assessment.
  
  • CKD eGFR < 60 for 3 months or more
• Proteinuria - Dipstick urine testing and urine culture
  
  • Proteinuria is an important diagnostic and prognostic marker - presence indicates higher risk for kidney disease and progression and CVD complications
• Imaging - Imaging of kidney can be useful - small kidneys with reduced cortical thickness, showing increases echogenicity, scarring, or multiple cysts is indicative of chronic process

Question 15

Prevention of CKD progession

Answer 15

• Hypertension- High BP is assocaited with a decline in kidney function. Patients should be encourgaed to maintain a healthy weight, reduce salt and alcohol intake, and to exercise regularly. ACEi and ARBs are recommended firt line agents, but often multiple medications are requried.
• Dietary changes - In early CKD obesity may be a problem. However, in advanced CKD malnutrition is a common issue (why protein restriction is controversal). Sodium intake should be restricted because the kidney losses its ability to excrete salt and water. Potassium and phosphate should also be restricted. Finally, fluid intake should be restricted to prevent volume overload.
• Smoking cessation
• Glycemic control

Question 16

CKD complications

Answer 16

• There are few manifestation of CKD in G1 and G2, but complications tend to occur as GFR declines below 60

1. Volume overload
2. Hyperkalemia
3. Metabolic acidosis
4. Mineral and bone disorders
5. Hypertension
6. Anemia
7. Dyslipidemia
8. Sexular dsyfunction

Question 17

Treatment of volume overload in CKD

Answer 17

• Sodium and intravascular volume balance tends to be maintained until GFR drops below 15. However, the kidney is less able to respond to rapid sodium intake and thus volume overload may occur.
• Treat with sodium restruction and a loop diuretic

Question 18

Treatment of Hyperkalemia in CKD

Answer 18

• Normal potassium levels are maintained as long as aldosterone secretion and distal flow are normal, hyperkalemia develops if patietn is oliguric or has another issue like high-potassium diet, increased tissue breakdown, or hypoaldosteronism (can be caused by ARBs and ACEi)
• Treat with low potassium diet and avoid use of medication that can elevate potassium (NSAIDs)

Question 19

Treatment of metabolic acidosis in CKD

Answer 19

• Metabolic acidosis is due to a failure or the kidney to excrete H⁺ and may be worsened by accumulation or organic acids and bicarb loss
• Can give alkali therapy (sodiu bicarbonate) to maintain serum bicarbonate concentration, unless contraindicated.

Question 20

Treatment of mineral and bone disorders in CKD

Answer 20

• Kidney is responsible for conversion of 1,25-OHVitD₃ into calcitrioil as well as for the uptake of 1,25-OHVitD₃ from filtrate to maintain serum levels. Thus, kidney damage results in a deficiency in 1,25-OHVitD₃ and calcitriol.
• 1,25-OHVitD₃ is responsible for stimulation the kidney to excrete phosphate and thus CKD is also associated with hyperphosphatemia.
• High phosphate stimualtes the parathyroid gland to release PTH (secondary hyperparathyroidism) and ultimately development of renal bone disease
• Phosphate-binding drugs may be needed
  
  • May result in vascular calcification due to increase Ca²⁺ intake from treatment hyperphosphatemic resulting in calcium - phosphorus products. (May increase coronary artery calcification).

Question 21

Treatment of anemia in CKD

Answer 21

• Anemia in CKD is due to a deficiency in EPO, but can also be contributed to by reduced iron and chronic inflammation. Anemia can result in many negative effects.
  
  • Worsen CHF by increased CO, worsening LV hypertrophy
  • Worsening kidney function
  • Reducing congition
• Can attempt to correct anemia by giving EPO, however, this is only recommened once HB drops below 100g/L and anyother underlying causes of anemia are addressed.

Question 22

Treatment of dyslipidemia in CKD

Answer 22

• Abnormal lipid metabolism is a common problem in CKD
• Can give patient a statin to lower plasma cholesterol

Question 23

sexual dysfunction in CKD

Answer 23

• Abnormalities in sexual and reproductive function are seen in CKD
• >50% of uremic males report ED, decreases libido, decline in frequency of intercourse
• Women report disturbances in menstration, fertility and amenorrhea once ESRD is reached.

Question 24

Complications of End Stage Renal Disease (ESRD)

Answer 24

1. Malnutrition - due to anorexia, decreased intestinal absorption and digestion, and metabolic acidosis
2. Uremic bleeding - increased bleeding tendency due to imparied platelet function. Generally treatment is not neccessary unless patient is actively bleeding or patient is about to have a surgery or biopsy. Treatment options = correction of anemia, administration of desmopressin, cryoprecipitate, estrogen, and initiation of dialysis.
3. Uremic pericarditis - fever, pleuritic chest pain, pericardial fricition rub. Indication to start dialysis.
4. Uremic neuropathy - dysfunction of central and peripheral nervous system - encephalopathy, polyneuropathy, and mononeuropathy
5. Thryoid dysfunction - Kidney normally plays a role in metabolism, degradation, and execretion of thrypid hormones. So, impaired kidney dunction effects the thyroid - may see low T3 levels.
6. Infection - patients with CKS are at increases risk of infection and patients should be vaccinated (flu, pneumonia, hepatitis) to reduce risks.

Question 25

CKD and AKI

Answer 25

• Patients with CKD are at increased risk of AKI and AKI is associated with more rapid progression to ESRD.
  
  • Radio contrast can increase risk of AKI and should only be used if benefits > risks
  • Patients should avoid certain medications, especially when sick.

Question 26

Renal Replacement Therapy (RRT)

Answer 26

• Many patients will progress to needing RRT
• Patients with an eGFR <20 or patients who are likely to have ESRD within 12 months should receive education about RRT (kidney failure = eGFR < 15 or dialysis).

1. Hemodialysis - arteriovenous fistula should be made (can take up to 12 weeks for vein to become appropriately arterialized).
2. Peritoneal dialysis - insertion of catheter to allow time for testing and training

• it is suggested that dialysis start when one or more of the following occur
  
  • Signs of symptoms caused by kidney failure (acid-base imbalance, puritus, etc.)
  • Inability to control volume status or BP
  • Progressive deterioration in nutritional status refractory to dietary intervention
  • Cognitive impariment
• Patients may also choose conservative management - palliative option