Chronic renal failure

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 chronic renal failure
definition:
- a pathophysiologic process with multiple etiologies
- reduced of nephron number and function
- A state, in which there has been an irreversible loss of
renal function, must depend upon dialysis or
transplantation
- “The world kidney day”, the second tuesday in March
every year
- Be a great social and economic burden on the whole
world, in USA, the cost on therapy for chronic kidney
disease has been rised to 20,000,000,000 dollars
- Be the leading killer to mankinds health
 definition
1.Azotemia - elevated blood urea nitrogen (BUN
>28mg/dL) and creatinine (Cr>1.5mg/dL)
2.Uremia - azotemia with symptoms or signs of renal
failure
3.End Stage Renal Disease (ESRD) - uremia requiring
transplantation or dialysis
4.Chronic Renal Failure (CRF) - irreversible kidney
dysfunction with azotemia >3 months
5.Creatinine Clearance (CCr) - the rate of filtration of
creatinine by the kidney (GFR marker)
6.Glomerular Filtration Rate (GFR) - the total rate of
filtration of blood by the kidney
7.Chronic kidney disease (CKD)
from National Kidney foundation, K-DOQI,
chronic kidney disease guidelines
 difference
Chronic renal failure?
chronic kidney disease?
Chronic kidney diseae including patients in
stage 1, GFR is normal or elevated
Aims: to appeal more attention to the
kidney disease, prevent the patients
develop renal failure quickly
 Major Causes of CRF

In china, glomerulonephritis, diabetic,

hypertension,and polycystic renal disease
are the leading underlying etiologies of CRD
or ESRD
But in the advanced countries, such as the
USA, diabetic is the leading cause, and then
hypertension, glomerulonephritis and
polycytic kidney disease
 Etiology
1.Primary glomerular diseases
a.focal and segmental GN
b.membranoproliferative GN
c.IgA nephropathy
d.membranous nephropathy
 Etiology
2.Secondary glomerular diseases
a.diabetic nephropathy
b.Amyloidosis
c.post-infectious GN
d.HIV-associated nephropathy
e.Collagen vascular disease
f.Sickle cell nephropathy
 Etiology
3.Tubulointerstitial nephritis
a.Drug hypersensitivity
b.heavy metals
c.analgesic nephropathy
d.Reflux/chronic pyelonephritis
e.Idiopathic
 Etiology
4.Hereditary diseases
a.polycystic kidney disease
b.medullary cystic disease
c.Alports syndrome
5.Obstuctive nephropathies
a.prostatic disease
b.retroperitoneal fibrosis/tumor
6.Vascular diseases
a.hypertensive nephrosclerosis
b.renal artery stenosis
 Common causes of Chronic
Renal Failure
Glomerulonephritis 25%
Diabetes Mellitus 25%
Hypertension 10%
Chronic pylonephritis/reflux 10%
Polycystic kidney disease 10%
Interstitial nephritis 5%
Obstruction 3%
Unknown 12%
 pathophysiology
initiating mechanisms -- specific to undrelying
etiology
progressive mechanisms --- non-specific
compensatory hypertrophy of surviving nephrons
– - adaptive hyperfiltration
– - mediated by vasoactive molecules, cytokines, growth factors
– - increased glomerular capillary pressure and flow
(hyperperfusion, hypertension, hyperfiltration)
– but, cannot last long
– sclerosis of remaining nephrons
 chronic renal failure
diabetes
hypertension damage to kidney
glomerulonephritis
loss of renal mass (nephrons)

hypertrophy & hyperfiltration of

remaining nephrons

“hypertension” of remaining nephrons

glomerulosclerosis
Pathophysiology and biochemistry
of uremia
Presently, the main toxins responsible for uremic
syndrome remain elusive
Urea may contribute to some symptoms, including:
anorexia, malaise, vomiting
Additional categories of nitrogenous excretory products
include urates, polyamines, etc. which molecular mass
(500-12000 Da, so-called middle molecules)
Polypeptide hormones, including parathyriod
hormone(PTH), insulin, glucagon,and prolactin rise with
renal failure, production of erythropoietin(EPO) and 1,25-
dihydroxycholecalciferol are reduced
Resulting in anemia, malnutrition, impaired metabolism
of carbohydrates, fats, and metabolic bone disease
Clinical manifestation of CRF
Disturbance in every organ system
Develop slowly and asymptomatic until
renal failure is far-advanced
Dialysis can reduce the severity of the
disturbance but is not a panacea
Some disturbance resulting from impaired
renal function fail to respond fully.
Sodium and water homeostasis
Disrupt glomerulotubular balance and promote
sodium retention
Excessive sodium ingestion
Lead to cumulative positive Na+ balance and
extracellular fluid volume expansion(ECFV)
Patients with CRD also have impaired renal
mechanisms for fluid conserving Na+ and
H2O ， will be prone to volume depletion,impair
residual renal fuction
Potassium homeostasis
Hyperkalemia
Cause:
constipation augmented dietary intake
protein catabolism hemolysis
hemorrhage transfusion of stored RBC
metabolic acidosis
medication(beta-blockers, ACE inhibitors
ARB, K+-sparing diuretics)
Metabolic acidosis
Is commom in CRF or ESRD
Cause:
a.reduced ability to produce ammonia
b.hyperkalemia further depresses ammonia
excretion
c.with tubulointerstitial disease
In most patients, the acidosis is mild, severe
acidosis may occur when the patient is
challenged with an excessive endogenous or
exogenous acid load or loses excessive alkali
 Renal osteodystrophy
Osteitis fibrosis
high bone turnover and high PTH levels
Osteomalacia and adynamic bone disease
low bone turnover with low or normal PTH levels,
excessive active vitamine D, which suppress
production of parathyroid hormone
Symptoms: bony pain and proximal muscle
weakness, spontaneous bone fractures can
occur that are slow to heal
Calcification of soft tissue and blood vessels
 signs of CRF/ESRD
1. osteodystrophy
failing kidney function

electrolyte imbalance

secondary hyperparathyroidism

“renal” osteodystrophy
 also
↓ GFR
↓ 1α -hydroxylase activity
↓ phosphorus excretion ↓ vit D activation

hyperphosphatemia ↓ Ca2+ intake in gastr

↓ Ca2+ & PO4 3- reabsorption
↑ PTH production in distal tubules
Secondary hyperparathyroidism

↑ osteoclast activity
osteitis fibrosis cystica
renal
slow bone mineralization
osteodystropy
osteomalacia
Cardiovascular abnormalities

The leading cause of morbility and mortality in

patients with CRD at all stages!
Ischemic cardiovascular disease
risk factors
traditional CKD-related
hypertention anemia
hypervolemia hyperphosphatemia
dyslipidemia hyperparathyroidism
smoking microinflammation
alcohol dialysis
age
over-weight
 Congestive heart failure
Cause:
a.myocardial ischemic disease
b.left ventricular hypertrophy
c.salt and water retention

heart failure and pulmonary edema

usually respond promptly to vigorous dialysis
 Hypertention and left ventricular
hypertrophy
cause:(hypertenyion)
a.volume overload is the major cause
b.elevation level of serum renin
cause:(LVF)
a.is the most ominous risk fator for morbility
and mortality in CRF
b.prolonged hypertention
c.fluid volume overload
 Pericarditis
a.Pericardial pain with respiratory
b.Accompanied with a friction rub
c.Electrocardiographic abnormalities include:
PR-interval depression
ST-segment elevation
d.Detected by echocardiography
e.Sometimes lead to cardiac tamponade
Hematologic abnormalities
Anemia
Observed beginning at stage 3 CRD and
universal at stage 4
Reasons:
a.insufficient production of EPO
b.iron and folate deficiency
c.severe hyperparathyroidism
d.inflammation
e.aluminum toxicity
f.shorten red cell survial
 Neuromuscular abnormalities
Cause: retained nitrogenous metabolities vt6

. and middle molecules as well as PTH

contribute to
Manifestations:
mind disturbance sleep disturbance
neuromuscular irritability: hiccups,cramps,chorea
Peripheral neuropathy
initially,sensory nerves are involved than motor
 Endocrine metabolic disturbance
a.Parathyroid function
b.Blood glucose slightly elevated
c.Plasma insulin slightly elevated
d.Many hypoglycemic drugs require dose
reduction
e.Metformin are contraindicated when
GFRdiminished by 25%-50%
f.In women,estrogen levels are low, inability to
carry pregnancies to term
g.In men, impotence, testosterone are
low,growth, sexual maturation is often impaired
 Dermatology abnormalities
a.Calciumphosphate deposition, secondary
hyperparathyroidism, and deposition of
pigmented metabolities or urochrome and urea
itself.
b.Pruritus
c.Skin necrosis
Evaluation and management
 History and physical examination
a.history: hypertension, diabetes,systemic
infection,inflammation, metabolic disease,
exposure to drugs and toxins, and family
history of renal disease
b.questions: appetite, diet, nausea, vomiting,
short of breath, edema, weight loss, muscule
cramps, pruritus
c.Physical examination:blood pressure,
funduscopy, abdomen palpation, prostate size
Laboratory investigation
a.Focus on a search for clues to an underlying
disease process and its continued activity
b.Immunologic tests for systemic lupus
erythematosus and vasculitis
c.Serum and urinary eletrophoresis to preclude
paraproteinemia
d.Tests for determine the stage and complication:
creatinine, GFR, urea, eletrolytes, alkaline
phosphatase to assess metabolic bone disease
24h urine collection for protein excretion
Imaging studies
a.Ultrasound examination: kidney size,
obstructive uropathy
b.Symmetric small kidneys support diagnosis of
CFR,and indicate irreversible
c.Normal size usually suggests acute renal failure
d.Asymmetric kidney size suggests unilateral
developmental abnormality or chronic
renovascular disease
e.MRI and doppler sonography are useful in
assess the renal arteries and veins
Renal biopsy
a.Reserved for patients with normal kidney
size,diagnosis cannot be made by invasive
means,or when the possibility of a reversible
underlying disease .
b.contraindication:bilateral small kidneys,
polycytic kidney disease, uncontroled
hypertension, urinary or perinephric infection,
bleeding diathesis, respiratory distress, and
morbid obesity
Establishing the diagnosis and etiology of
CRD
a.To distinguish newly diagnosed CRD from
acute renal failure
b.Chronic metabolic bone disease with
hyperphosphatemia, hypocalcemia, elevated
PTH level,normocytic anemia, bilateral reduced
kidney size, strongly support CRF
c.In advanced stages of CRD, definitive etiology
becomes less feasible and is also of less
therapeutic significance
treatment
1.Specific treatement aimed at selected
underlying etiology of CFR,such as lupus
vasculitis,optimal time for such therapy can
made the function of the kidney reversible
2.To find out superimposed acute processes that
lead to an acute and reversible decline in GFR
3.Include volume depletion, uncontroled
hypertension, nephrotoxin of medications,and
so on
4.Slowing the progression of CRD, aimed to
stabilize the GFR or reduce the annual rate of
decline
Reversible causes of renal failure

reversible factors diagnostic clues

Infection urine culture and sensitivity tests

obstruction catheterization and renal ultrasound
EFVD orthostatic blood pressure
hyperkalemia serum electrilytes examination
hypercalcemia serum electrilytes examination
nephrotoxic agents drug history
hypertension blood pressure
congestive heart failure physical examination chest X-ray
Protein restriction
1.Aim:ameliorating the complications of uremia
to slow the rate of decline of nephron injury.
2. Protein requirement of 0.6g/d.kg is
recommended
3.Dietary protein should be higher in essential
amino acids
4.Energy requirements in the rage of 35kcal/kg.d
are recommended
Reducing intraglomerular hypertension and
proteinuria
1.aim:to slow the progression of nephron injury
by ameliorating intraglomerular hypertension
and hypertrophy
2.Proteinuria is considered a risk factor for
progressive nephron injury
3.ACEI inhibitors and (angiotensin receptor
blockers(ARB) are effective to reduce
proteinuria, second-line therapeutic approch is
calcium channel blockers
Disorder of water, sodium, potassium, and acidosis
1.Restriction of dietary intake and use of loop diuretics
2.Attention : excessive use of diuretics cause
hypovolemia, thus lead to further decline in GFR
3.hyperkalemia: avoid potassium-containing or retaining
medications,and dietary restriction of
potassium,potassium-binding resins can promote
gastrointestinal potassium loss
4.Metabolic acidosis:serum bicarbonate level should be
maintained at >21mmol/l, sodium bicarbonate and
calcium bicarbonate should be given to the patients
Disorder of mineral metabolism
1.Dietary phosphorus restriction should be less
than 1000mg/d
2.Oral phosphorus-binding agents such as
calcium carbonate given in divided doses three
or four times dialy with meals
3.Vitamin D should be given the patients with
hyperparathyroidism
4.Since adynamic bone disease is often a
consequence of overzealous treatment of
hyperparathyroidism, PTH should not be
<120pg/ml
Hypertension
1.Should be controled to 130/80-85mmHg
2.In CRD patients with diabetes or proteinuria
>1.0g/d,further reduced to 125/75mmHg
3.Volume control with salt restriction and diuretics
is the mainstay of therapy
4.Because of the vascular-renal protective
benefit, ACE inhibitors and ARB are
recommended firstly.
Cardiovascular disease
1.Hyperhomocysteinemia may repond to vitamin
therapy
2.Hyperlipidemia: HMG-coA reductase inhibitor.
simvastatin and lovastatin can be selected
Uremic pericarditis
1.Should be intensify the dialysis in those already
on dialysis
2.Pericardiectomy should be considered only if
more conservative measures fail
Congestive heart failure
1.Salt and water intake should be control
2.Diuretics are of value, loop diuretics often used
3.Digoxin should be used with caution
4.ACEI and ARB are effective in hear failure,but
serum creatinine and potassium should be
checked within 5-14 days
Anemia
1.Recombinant human EPO
2.Before treatment of EPO, iron stores should be
available.
3.Anemia resistant to recommended doses of
EPO often suggest:
inadequate dialysis, hyperparathyroidism
aluminum toxicity, chronic blood loss
malnutrition, chronic infection
Medication dose adjustment
1.Drugs that >70% excretion is by nonrenal route,
adjustment should not be needed
2.Meperidine, metformin, and other drugs with a
renal route of excretion
3.Many drugs have nephrotoxicity,such as
NSAIDs,should be forbiden.
4.Drugs aggravate the tendency to hyperkalemia,
and further reduce GFR should be used with
caution.
Renal replacement therapy
1.When conservative management of ESRD is
inadequate,hemodialysis, peritoneal
dialysis,and kidney transplantation are needed
2.When GFR <10ml/min, require renal
replacement therapy
3.Absolute indication:
severe volume overload
severe hyperkalemia and acidosis
encephalopathy
pericarditis
symptomatic uremia
• Procedure for Chronic Hemodialysis
b. Blood is run through a semi-
permeable filter membrane bathed in
dialysate
c. Composition of the dialysate is altered
to adjust electrolyte parameters
d. Electrolytes and some toxins pass
through filter
e. By controlling flow rates (pressures),
patient's intravascular volume can be
reduced
f. Most chronic hemodialysis patients
receive 3 hours dialysis 3 days per
week
Peritoneal dialysis
1.Place a peritoneal catheter that allow infusion
of a dialysate solution into the abdominal
cavity.which served as “artificial kidney”
2.Exchange dialysate
3.The most common complication is peritonitis
Kidney transplantation
With the advent of more potent and well-
tolerated immunosuppressive drugs,kidney
transplantation offers the potential for nearly
complete rehabilitation