Chronic Kidney Disease Flashcards
What are some major functions of the kidneys?
Excretion of wastes/toxic products
Fluid balance
Electrolyte balance
Acid base balance
Calcium homeostasis
Regulation of RBC production
What is the definition of chronic kidney disease?
Abnormalities in kidney structure or function, present for 3 months or longer, and with implications for health
How is the prognosis of chronic kidney disease rated?
Classification system based mainly on GFR and Albumin:Creatinine ratio
Is ESRD an early stage of chronic kidney disease?
No, it is the final stage
Defined as GFR<15mL/min
These patients need dialysis or kidney transplant to live
What are some risk factors for chronic kidney disease?
The following are the main three risk factors:
Diabetes (damages glomerular structure)
High BP
CV disease
How do symptoms of chronic kidney disease progress?
They develop over time, kidneys can adequately operate until below 50% full functionality. This is where symptoms begin to develop
What are some symptoms and signs of chronic kidney disease?
Can be classified into two groups:
“Caused by the build up of waste” (loss of appetite; fatigue and weakness; Sleep problems; Muscle twitches and cramps)
“Due to not enough water leaving the body”)
(Swelliong of feet and ankles; inflammed organs due to fluid build up around the organs)
What is the GFR range for G1 CKD?
Higher than 90mL/min (Normal or high)
What is the GFR range for G2 CKD?
60-89mL/min (Mildly decreased)
Are G1 and G2 CKD symptomatic conditions?
No, the body can tolerate 50% GFR without onset of side effects
What is the GFR range for G3a CKD?
45-59mL/min (MIldly to moderately decreased)
What is the GFR range for G3b CKD?
30-44mL/min (Moderately to severely decreased)
What is the GFR range for G4 CKD?
15-29mL/min (Severely decreased)
What is the GFR range for G5 CKD?
below 15 (Kidney failure)
What is the Albumin:creatinine ratio (ACR) for A1 CKD?
less than 30 (normal to mildly increased)
What is the ACR for A2 CKD?
30-300 (moderately increased)
What is the ACR for A3 CKD?
more than 300 (severely increased)
What are some causes of CKD?
Glomerular disease
Tubulointerstitial disease
Vascular diseases
Cystic and congenital diseases
What are the clinical manifestation of CKD?
Accumulation of toxins
Consequences of non-excretory functions (fluid/electrolytes, hormones)
Progressive inflammation
Is identifying CKD at an early stage easy?
No, the condition is usually asymptomatic.
What does normal GFR decline look like?
GFR peaks at age 20 (120mL/min), but declines by 1mL/min every year
What factors affect the progression of CKD?
The original cause of CKD
GFR at time of diagnosis
Degree of albuminuria
Presence of comorbid conditions:
Hypertension
Diabetes
Congestive heart failure
Ischemic heart failure
COPD
What exactly is happening in the kidneys in CKD?
Irreversible injury to nephrons, remaining nephrons are in overdrive
Overworked nephrons caused damage and reduces GFR even faster
What causes uremia?
Uremia is a serious complication of CKD and AKI, and it involves the accumlation of hundreds of toxins
Creatinine and urea can be viewed as markers for other retained waste products
What happens to Na+ balance in CKD?
IN CKD, Na+ and water excretion is not adjusted based on intake.
Intake exceeds excretion, resulting in Na+ and water retention
How are the consequences of fluid retention?
Symptoms develop slowly starting with eczema, but eventuallly, it can become very difficult to manage, contributing to HF, HTN, edema, and weight gain (increased water mass)
Why can diuretic drugs have reduced efficacy in CKD?
IN CKD, the tubules are damaged. The ion transporters that would be inhibited by diuretic drugs are damaged or do not exist. This means that the diuretic drugs are not able to bind to many receptors
Can any drug class used in CKD treatment cause deafness?
High doses of Loop diuretics are ototoxic, and could cause deafness following long-term use
How is end stage renal disease (ESRD) diagnosed?
Kidney permanently fail to work (no urine production)
Blood tests (Blood cell and electrolyte levels; and kidney function)
Urine tests
Sonography
Kidney biopsy
CT Scan
What is the most common primary disease that causes ESRD?
Diabetes is the number one cause, closely followed by hypertension
Kidney disease on its own is much lower than the first two
What are some treatment options for ESRD?
Dialysis (not cure):
Peritoneal dialysis
Hemodialysis
Kidney transplantation
How does hypertension worsen CKD?
Chronic glomerular hypertension can lead to hypertrophy to tissues due to increased pressure, but subsequent loss of nephrons due to damage
High glomerular pressure also promotes tissue remodelling, a change that leads to protein leakage into the nephrons. Proteins are toxic in the tubules
What is the expected albumin:urea ratio in late CKD?
Above 300, up to 1000
What are some common measures taken to slow hypertension from worsening CKD?
Salt restriction
ACEi and ARBs
How can proteinuria be identified?
ACR (albumin:creatinine ratio)
Protein dipstick (urine test)
Blood can be lost in the urine, so blood volume could be lower than normal
What is the impact of diabetes on CKD?
Diabetes is associated with glomerular mesangial matrix expansion, and subsequent renal vessel damage from being distorted by the expansion of mesangial cells.
High blood sugar also can glycosylate tissues, a function that can directly damage the tissues
How are cardiovascular disease and CKDrelated?
Most CKD patients, actually die from a cardiovascular problem before the reach the final stages of CKD
Reduction of CV risk can slow progression of CKD
What is the relationship between atherosclerosis and CKD?
CKD patients usually have classic risk factors for atherosclerosis (HTN, lipid, SNS tone).
Are ACEi/ARBs useful in CKD?
Yes, the benefit increases in people with more severe disease
In lower risk people, (lower SCr and GFR) other drugs show similar protection
When does hyperkalemia develop in CKD?
When GFR falls below 5mL/min, hyperkalemia becomes a serious problem
How is hyperkalemia in CKD resolved with pharmaceutical agents?
K-wasting diuretics (TZD & Loop diuretics)
Reduce use of K-sparing medications
Potassium-binding resins
How do potassium-binding resins reverse hyperkalemia?
Na+ or Ca2+ polystyrene sulfonate will bind to K+, in exchange for Na+ or Ca2+
These agents run the risk of elevating Na+ or Ca2+
What happens to acid/base balance in patients with CKD?
Under normal function, the kidneys are responsible for maintaining bicarbonate concentration. In CKD, the kidneys have a diminished capacity to excrete acid and to generate base. Blood pH steadily increases in patients with CKD
What are fixed acids and what is their relationship to CKD patients?
Lactic acid and ketones are not volatile, so they do not react with usual excitatory mechanisms. The kidneys are responsible for their excretion. Patients with CKD have a buildup of fixed acids (lower pH)
How is ammonia from protein metabolism excreted?
Circulating ammonia molecules are combined with CO2 in the liver to form urea.
Urea is highly soluble and is easily excreted by the kidneys
What is metabolic acidosis?
Due to the build up of protons in the blood, ph decreases.
Because blood ph is low (acidic), free bicarbonate (base) will bind to the acid in attempt to neutralize the pH. This means that bicarbonate levels are lower
Because metabolic acidosis is a disease that can be caused by kidney dysfunction, PaO2 is normal
When does metabolic acidosis begin in CKD?
Normally mild until GFR falls below 20ml/min
sodium bicarbonate (baking soda) can be used to reveres metabolic acidosis, but it can also deliver large amounts of Na+. This can add load to her kidneys and worsen some of the risk factor conditions
How are the kidneys important in Vitamin D activity?
The kidneys activate Vitamin D into its active form.
In CKD, this process has been damaged
What are the effects of parathyroid hormones on the kidneys?
When Ca2+ falls, the parathyroid gland secretes PTH. PTH has effects on the function of kidneys and bone.
KIdney functions:
Promotes renal tubular Ca2+ reabsorption and phosphate excretion. PTH also stimulates the conversion of VItamin D into its active form
Bone functions:
Promotes catabolism of bone to release Ca2+ and P into the bloodstream (increase blood concentrations)
What happens in CKD patients with functions associated with PTH?
In damages kidneys, Ca2+ reabsorption does not occur. This means the PTH promotes the breakdown of bones to maintain Ca2+ homeostasis
Is PTH release inhibited by kidney activated Vitamin D?
Yes
In patients with CKD, their kidneys have a lower ability to produce activated Vitamin D. This means that they have a reduced ability to reduce PTH levels. Elevated PTH levels cause Ca2+ and P loss from the bones. This can result in weak bones in CKD patients
How does reduced reabsorption of Ca2+ and P by the kidneys in CKD patients affect bone mass?
These patients are not able to reabsorb Ca2+ and P and it is lost in the urine. This prompts PTH to break down bones for Ca2+ and P.
How are the kidneys and RBC production related?
Kidneys contain specialized cells that can detect low oxygen levels in the body. IN response to hypoxia, the kidneys release erythropoietin.
Erythropoietin is resoponsible for promoting the production of RBCs, in advanced kidneys disease the production of RBC is reduced
What happens if RBC production no longer has enough stimulation?
Anemia often begins when GFR falls below 30-45 mL/min (due to low production of erythropoietin)
To treat this type of anemia, patients are given iron supplements, erythropoietin-stimulating agents, and an agent that extends the duration of the above drugs
What are some drug dosing considerations in patients with CKD?
Approximately half of patients with a GFR below 60ml/min are at risk for adverse drug reactions.
The following factors make patients more susceptible to adverse drug reactions:
Old age
ACEi/ARB use
Diabetes
Advanced CKD
What are some pharmacokinetic and pharmacodynamic considerations in CKD?
Increased volume of distribution
Metabolite accumulation
NO-renal clearance (billiary excretion)
Loading and maintainance dose
Serum drug monitoring
When is dialysis therapy needed in CKD?
Uremic symptoms are severe
Hyperkalemia is unresponsive to therapy/diet or drug modification
Volume expansion becomes untreatable
Chronic acidosis
GFR is below 10mL/min (kidney failure)
