Chapter 28

what is chronic kidney disease (CKD)

irreversible decrease in glomerular, tubular and endocrine functions of the kidney for longer than 3 months AND evidence of kidney damage (albuminuria or abnormal biopsy) OR GFR < 60 ml/min/1.73m²

different stags of CKD

stage 1: damaged (at risk) with normal or increased GFR (90 mL/min/1.73m²)

stage 2: mild reduction in GFR (60-89)

stage 3: moderate reduction in GFR (30-59)

Stage 4: severe reduction in GFR (15-29)

stage 5: failure (GFR <15 or dialysis)

what is the prevalence of CKD

15% in the general U.S. population

Chronic kidney disease (CKD) is a progressive and irreversible

true

Etiology of CKD

• diabetic kidney disease is the most common cause (40%; 1 in 4 adults with diabetes has CKD)

• Chronic high blood pressure (20%)

• Glomerulonephritis (15%)

• Polycystic kidney disease (10%)

• Interstitial nephritis (10%)

at what stage are patients diagnosed as having CKD

beginning with stage 3 according to GFR, regardless of the existence of kidney damage

Medicare spending for patients with CKD ages 65 and older exceeded $50 billion in 2013 and represented 20% of all Medicare spending in this age group 

true 

How is the progression of CKD monitored

• measuring changes in GFR

• determining the presence and degree of proteinuria

• examining urinary sediment for RBC and WBC

• measuring serum creatinine levels 

• performing imaging studies with renal ultrasonography 

stages of CKD with no symptoms

stages 1-3

stages of CKD that have symptoms

stages 4-5

symptoms and signs of stage 4-5 CKD

• disturbances in water/electrolyte balance

• metabolic and endocrine changes become clinically manifest 

  • abnormal handling of salt and water

    • sodium and water retention

  • abnormal handling of acid/base balance causes acidosis too little

    • H+ secretion

  • Reduced Erythropoietin causes anemia

    • reduced RBC production

Clinical manifestations of abnormal handling of salt and water

• generalized edema

• fluid in the lungs

• high BP

• palpitations

• muscle pain

Clinical manifestations of abnormal handling of acid/base causes acidosis 

• protein energy malnutrition

• loss of lean body mass

• muscle weakness

clinical manifestations of reduced erythropoietin production causing anemai 

• fatigue 

• reduced exercise capacity

• reduced quality of life

• impaired cognitive function

Decreased renal reserve

75% nephron loss

• remaining nephrons accommodate additional workload 

• no signs/symptoms

• BUN and creatinine normal

• may not be diagnosed 

Renal insufficiency 

75-90% 

• kidney is unable to concentrate the filtrate so polyuria occurs 

• nocturia

• slight elevation of BUN and creatinine 

End stage renal disease

> 90%

• kidney is unable to fulfil its multiple roles 

• uremia

• fluid and electrolyte abnormalities

• osteodystrophy

• anemia

• dialysis or translation is essential 

why would polyuria occur

Kidney is unable to concentrate the filtrate

cardiovascular disease is both a risk factor and a complication of CKD

true

Complications of CKD

• hypertension and cardiovascular disease

(each can cause the other: CKD, hypertension, CD)

• uremic syndrome

• metabolic acidosis 

• electrolyte imbalances

• mineral and bone disorders 

• anemia

• depression 

do most people with CKD die from kidney failure

no, most die from the results of cardiovascular disease

Complications of uremia

• urea and other toxins accumulate in the blood and can cause life-threatening problems 

  • gastro-intestinal bleeding due to platelet dysfunction caused by urea

• Inflammation of the pericardium (uremic pericarditis)

  • chest pain 

• Urea effect on the CNS (mechanisms unclear)

  • headache, confusion, coma

• patients must get dialysis no matter what GFR is 

What are some urea effects on the CNS

• headache 

• confusion

• coma 

CKD associated bone disorders

usually without symptoms, but pain and fracture can be seen

• hyperphosphatemia (high blood phosphate)

• Hypocalcemia (low blood calcium)

• secondary hyperparathyroidism (excess parathyroid hormone production)

Hyperphosphatemia

high blood phosphate

• bone disorder associated with CKD

• damaged kidneys fail to excrete phosphate

• extra phosphate in blood binds calcium taking it away from the bones

• increased risk of cardiovascular disease 

hypocalcemia

Low blood calcium

• bone disorder associated with CKD 

• impaired vitamin D activation → reduced calcium absorption in the kidney

calcium is needed for bone strength

Secondary hyperparathyroidism 

excess parathyroid hormone production 

• bone disorder associated with CKD

• to compensate for low calcium due to low active vitamin D and hyperphosphatemia, the parathyroid glands produce extra parathyroid hormone

• causes the release of more calcium from the bones (so bones become weaker)

CKD associated anemia

• development of anemia is anticipated in patients with CKD

• most significant is lack of erythropoietin production by the kidney

• problem is escalated by malnutrition

  • iron, folate, Vitamin B₁₂

• Uremia reduced the normal life expectancy of RBC

most significant when assuming CKD associated anemia

the lack of erythropoietin production by the kidney

CKD water/sodium balance

sodium/water retention, hypertension, edema

treatment → Na restriction and diuretics 

CKD balanced potassium excretion

high blood potassium and palpitations

treatment → low potassium diet

CKD balanced acid excretion

metabolic acidosis

treatment → sodium bicarbonate 

CKD calcium phosphate balance

high PO4, high PTH, low act-vit D, low Ca++

treatment → phosphate binders, low phosphate diet, calcimimetics

CKD RBC production

anemia

treatment → erythropoietin iron

Treatment options for end stage renal disease CKD5

• hemodialysis (3-4 times per week = 72K per year)

• Peritoneal dialysis (less expensive)

• Kidney transplant 

Risk factors for developing advanced CKD

• obesity 

• SES

• smoking

• Nephrotoxins and NSAIDS

• high BP

• Diabetes mellitus

• periodontal disease

• sleep apnea

what is key towards addressing the major health problem of CKD

identification of at-risk individuals and early detection

Acute kidney injury

was known as acute kidney failure

• AKI now 

• Broad spectrum of kidney diseases ranging from minor changes in renal function to complete renal failure requiring renal replacement therapy 

What does AKI do

sudden reduction of kidney function causing:

• disruptions in fluid, electrolyte, and acid-base balances

• retention of nitrogenous waste products

• increased serum creatinine 

• decreased glomerular filtration rate (GFR)

What does the Kidney Disease improving Global Outcomes (KIDGO) define AKI as

• increase in serum creatinine by > 0.3 mg/dl within 48 hrs

• Increase in serum creatinine to > 1.5 times baseline within the prior to 7 days 

• urine volume < 0.5 mL/kg/h for 6 hours 

RIFLE classification

for AKI

• R → risk of injury

• I → injury

• F → failure

• L → loss of function

• E → end stage kidney disease 

First 3 stages of RIFLE indicate what

severity of kidney injury

what do last 2 stages of RIFLE indicate

represent patient outcomes

what is the incidence of AKI in hospitalized patients

15-23% with higher rates in the elderly

Etiology and pathophysiology of AKI

• abrupt reduction in renal function producing an accumulation of waste materials in the blood

what pre-existing conditions increase the risk of developing AKI

• preexisting kidney impairment

• CVD

• Hypertension

• Diabetes

• HF

• Malignancies

• Nephrotoxic drugs 

What does renal blood flow do with age

decreases → 10% per decade

What are the 3 sites of disruption in AKI

1) renal perfusion (prerenal)

2) Urine flow distal to the kidney (postrenal)

3) circumstances within the kidney blood vessels, tubules, glomeruli, or interstitium (intrinsic/intrarenal) 

distinction between the sites helps determine appropriate therapy 

What is prerenal kidney injury

because of conditions that diminish perfusion of the kidney

• hypovolemia, hypotension, HF

• renal artery obstruction

• fever, vomit, diarrhea

• burns

• overuse of diuretics

• edema, ascites

• drugs: ACE inhibitors, angiotensin II blockers, NSAID

Is characterized by low GFR, oliguria, high urine specific gravity and osmolality

How does the kidney tolerate significant reduction in perfusion

can tolerate up to 25%

Postrenal kidney injury

• because of obstruction within the urinary colleting system distal to the kidney

• elevated pressure in bowman capsule

• impeded glomerular filtration 

• clinical findings based on duration of obstruction

• prolonged postrenal ARF leads to acute tubular necrosis (intrinsic) and if continues leads to irreversible kidney damage 

Intrinsic/intrarenal kidney injury

because of a primary dysfunction of the nephrons and the kidney itself

• most common problem in renal tubules resulting in acute tubular necrosis (ATN)

• may also occur in glomerular, vascular, or intestinal etiologies 

ATN

Acute tubular

• causes:

  • Nephrotoxic insult (contrast media)

  • Ischemic insults (sepsis) 

What are the two interrelated pathophysiologic processes of intrinsic/intrarenal kidney injury

1) Vascular: renal blood flow decrease due to hypertensive episode or inflammation or obstruction 

• causes hypoxia, vasoconstriction

2) Tubular: inflammation and reperfusion injury

• causes casts, obstructs urine low, tubular back leak 

what two kidney injuries will progress to intrinsic/intrarenal kidney injury if not corrected within a few hours

1) Prerenal

2) Postrenal 

Can intrinsic intrarenal kidney injury repair itself

yes, but if sustained can lead to end-stage renal disease

Clinical presentation of AKI

Divided into 3 phases

1) Prodromal

2) Oliguric

3) Post-oliguric 

• varies with the phase

• lab findings can help differentiate prerenal from intrinsic/intrarenal kidney injury

Prodromal phase of AKI

• normal or declining urine output

• serum BUN and creatine start to rise

• insult to the kidney has occurred and the duration of this phase will vary depending on 

  • cause of injury

  • amount of toxin ingested

  • duration and severity of the hypotension 

Oliguric phase of AKI

• can las up to 8 weeks with usual urine output 50 to 400 mL/day

• Characterized by oliguria, progressive uremia, decreased GFR, and hypervolemia 

  • have signs/symptoms of fluid excess, hyperkalemia, uremic syndrome

  • those with severe can become anuric (no urine output) 

• Sodium is lost in urine because reabsorption mechanism is impaired

• other electrolyte (potassium, magnesium, and phosphorous) are retained in the blood

• hyperkalemia is the greatest concern

  • levels less than double of normal can be fatal

• As GFR drops, organic metabolic waste products accumulate

  • uremic solutes are found to be responsible for my of the signs and symptoms = uremic syndrome

Postoliguric phase

• termination of oliguric phase represents renal recovery

• not all recover

• urine volume increases → diuresis

• tubular function improves fluid volume deficit until kidneys recover

• could last a week but full recover is about a year

  • full recovery: creatinine and BUN normal

  • usually degree of renal insufficiency persists