Transcript Overview of the management of chronic kidney disease in adults

Overview of chronic
kidney disease in
adults
Chronic kidney disease
• Chronic kidney disease is a worldwide public health
problem.
• there is a rising incidence and prevalence of kidney
failure
•
The number of patients enrolled in the ESRD
program has increased from approximately 10,000
beneficiaries in 1973 to 86,354 in 1983, and to
506,256 as of December 31, 2006
• Patients with ESRD consume a disproportionate
share of health care resources.
• The total cost of the ESRD program in the US was
approximately $22.7 billion in 2006.
• The projected number of ESRD patients by the year
2010 has been estimated to be 651,330 and the total
Medicare ESRD program cost in excess of $28 billion
dollars
• Despite the magnitude of the resources committed
to the treatment of ESRD and the substantial
improvements in the quality of dialysis therapy,
these patients experience significant mortality and
morbidity, and a reduced quality of life.
• Unfortunately, CKD, which is highly prevalent, is
commonly "under-diagnosed" and/or "undertreated", resulting in lost opportunities for
prevention
The National Kidney Foundation - Kidney Disease Outcomes
Quality Initiative (NKF-K/DOQI) workgroup has defined CKD;
• The presence of markers of kidney damage for ≥3
months, as defined by structural or functional
abnormalities of the kidney with or without decreased
glomerular filtration rate (GFR), that can lead to
decreased GFR, manifest by abnormalities in the
composition of blood or urine, or abnormalities in
imaging tests
OR
• The presence of GFR <60 mL/min/1.73 m2 for ≥3
months, with or without other signs of kidney damage
• Stage 1 disease is defined by a normal GFR (greater than 90
mL/min per 1.73 m2) and persistent albuminuria (1.8 percent).
• Stage 2 disease is a GFR between 60 to 89 mL/min and
persistent albuminuria (3.2 percent).
• Stage 3 disease is a GFR between 30 and 59 mL/min (7.7
percent).
• Stage 4 disease is a GFR between 15 and 29 mL/min (0.35
percent).
• Stage 5 disease is a GFR of less than 15 mL/min or end-stage
renal disease (2.4 percent).
• The rate of progression of chronic renal
disease from one major stage to another
varies based upon the underlying disease,
presence or absence of comorbid conditions,
treatments, socioeconomic status, individual
genetics, ethnicity, and other factors.
• The albumin/creatinine ratio combined
with estimated GFR may provide a better
predictor of patients at risk for
progression to ESRD than estimated
GFR alone
• For small changes in serum creatinine, which
may be clinically significant, the
measurements are most reliable if performed
in the same laboratory.
• By comparison, changes in serum creatinine
of ±0.3 mg/dL measured in different
laboratories may represent variations in the
assay rather than the GFR
• Normal individuals demonstrate a
decline in renal function over time.
•
Above the age of 30, this amounts to
an average decrease of 0.7 to 0.9
mL/min in the glomerular filtration rate
per year
SCREENING FOR CKD
Screening for CKD is justified because:
• Various
therapeutic
interventions
effective in slowing or preventing
progression toward kidney failure.
are
the
• CKD can be detected in its earlier stages via
laboratory testing.
•
However, because of the relatively low
prevalence of CKD, massive screening in the
general population is not recommended
In general, the presence of the following risk factors for CKD
should provoke formal testing for CKD:
• History of diabetes, cardiovascular disease, hypertension,
hyperlipidemia, obesity, metabolic syndrome, smoking, HIV or
hepatitis C virus infection, and malignancy
• Family history of CKD
• Age >60 years
• Treatment with potentially nephrotoxic drugs
• he kidney is able to adapt to damage by increasing
the filtration rate in the remaining normal nephrons,
a process called adaptive hyperfiltration.
• As a result, the patient with mild renal insufficiency
often has a normal or near-normal serum creatinine
• Adaptive hyperfiltration, although initially beneficial,
appears to result in long-term damage to the
glomeruli of the remaining nephrons, which is
manifest by proteinuria and progressive renal
insufficiency
• The gradual decline in function in patients with
(CKD) is initially asymptomatic. However, different
signs and symptoms may be observed with
advanced renal dysfunction, including volume
overload, ….
• Manifestations of the uremic state include anorexia,
nausea, vomiting, pericarditis, peripheral
neuropathy, and central nervous system
abnormalities
• No direct correlation exists between the absolute
serum levels of blood urea nitrogen (BUN) or
creatinine, and the development of these symptoms.
• ASSOCIATION WITH CARDIOVASCULAR DISEASE
• Patients with CKD are at increased risk for a variety
of non-cardiovascular diseases, including infection
and malignancy
• Careful attention should be paid to preventive
measures such as influenza and pneumococcal
immunization, and age-appropriate screening for
malignancy
GENERAL MANAGEMENT OF
CHRONIC KIDNEY DISEASE
• Treatment of reversible causes of
renal dysfunction
• Preventing or slowing the
progression of renal disease
• Treatment of the complications of
renal dysfunction
• Identification and adequate
preparation of the patient in
whom renal replacement therapy
will be required
• Reversible causes of renal
dysfunction
Slowing the rate of progression
• Once renal injury has occurred, independent of
etiology, the decline in GFR can be accelerated by
hypertension,
proteinuria,
and
possibly
by
dyslipidemia ,metabolic acidosis
• The rate of decline in GFR can be decelerated with
early intervention. Perhaps the most successful
intervention is the reduction of blood pressure
• intraglomerular
hypertension
and
glomerular
hypertrophy leading to glomerular scarring
• glomerular damage and proteinuria typically occur
with progressive renal failure, even in primary TID
• In diabetic nephropathy and nondiabetic chronic
kidney diseases administration of ACE inhibitors or
ARBs slows the progression of chronic kidney
disease, with the greatest benefit in patients with
higher degrees of proteinuria
• the benefit is likely to be greatest if begun before a
great deal of irreversible scar has occurred.
• Thus, protective therapy has the greatest impact if it
is initiated relatively early in the course, before the
serum creatinine concentration exceeds 1.2 and 1.5
mg/dL in women and men, respectively, or the GFR is
less than 60 mL/min per 1.73 m2.
• ARBs are as effective as ACE inhibitors in reducing
protein excretion in patients with chronic kidney
disease
•
The reduction in proteinuria appears to be greater
when ACE inhibitors are used in combination with
ARBs than with either drug alone
•
However, it has not been proven that combination
therapy improves renal outcomes and adverse
effects are more common.
• It is not known whether the benefits
from ACE inhibitors/ARBs in
proteinuric chronic kidney disease
extend to patients older than 70 years
older patients are more likely to have
adverse effects from therapy (acute
kidney injury and hyperkalemia)
• ACE inhibitors and ARBs can cause a decline in
renal function and a rise in plasma potassium that
typically occur soon after the onset of therapy.
• An elevation in serum creatinine of as much as 30 to
35 percent above baseline that stabilizes within the
first two to four months of therapy is considered
acceptable and not a reason to discontinue therapy
with these drugs
• However, a repeat plasma creatinine and potassium
should be measured within three to five days.
• A high salt intake blunts the antiproteinuric effects
of angiotensin inhibitors and calcium channel
blockers, even when blood pressure reduction
seems appropriate
• Thus, patients on ACE inhibitors or ARBs who do
not have sufficient reduction in proteinuria despite
appropriate blood pressure goals should be
instructed to take a low sodium diet.
• reduction in protein excretion to less
than 500 to 1000 mg/day; or a minimum
reduction of at least 60 percent of
baseline values.
• reduction in blood pressure to less
than 130/80 mmHg.
• Caution is advised about lowering the
systolic blood pressure below 110
mmHg.
Protein restriction and
progression of chronic
kidney disease
• The optimal level of protein intake has not been
determined but it may be reasonable to restrict
intake to 0.8 to 1.0 g/kg per day of high biologic
value protein
• Some recommend even lower levels, such as 0.6 to
0.75 g/kg per day of high value protein, with close
supervision and dietary counseling
• an increase in the GFR can be induced by animal
protein and by amino acid mixtures
• vegetable protein and egg whites alone produce
little or no effect ( little hemodynamic activity)
• lower concentrations of the amino acids that cause
renal vasodilatation (such as glycine and alanine)
and lesser stimulation of vasodilator prostaglandins
may be involved
MECHANISM OF PROTEIN-INDUCED
HYPERFILTRATION
• Enhanced secretion of glucagons ,insulin-like growth
factor I (IGF-I) and kinins
direct renal vasodilator that can increase both RBF
and the GFR
• alterations in renin-angiotensin system
• Intrarenal effects —TGF may contribute to proteininduced hyperfiltration
•
Nutritional studies in patients with
CKD suggest that protein intake can be
safely lowered to 0.6 g/kg per day.
•
However, a very low protein diet has
been
associated
with
increased
mortality over the long term
• Protein-energy wasting can be diagnosed if three
characteristics are present;
• Low serum albumin, pre-albumin or cholesterol
• Reduced body mass (low or reduced body or fat
mass or weight loss)
• Reduced muscle mass (muscle wasting, reduced
mid-arm muscle circumference)
• Serum transferrin, which is used as a marker of
protein adequacy in general population, is not useful
in CKD patients
• Patients with CKD who are on a protein restricted diet
should be carefully monitored with close follow-up
every three to six months for adequate caloric intake
and evidence of protein malnutrition. (body weight ,
serum albumin, pre-albumin, and cholesterol ).
•
More frequent monitoring (ie, monthly) may be
necessary in patients with advanced CKD (ie, stages 4
and 5).
• Both hyperlipidemia and metabolic acidosis should be
treated
• Smoking cessation should be encouraged,
• Smoking enhanced risk of developing kidney disease
(primarily nephrosclerosis)
• Obesity — There is an association
between
morbid
obesity
and
proteinuria.
• an association between a body mass
index over 35 kg/m2 and proteinuria
• The relationship between body weight
and glomerular filtration rate is less
clear.
Treatment of the complications of
renal dysfunction
• A wide range of disorders may develop
as a consequence of the loss of renal
function. These include disorders of
fluid and electrolyte balance, such as
volume
overload,
hyperkalemia,
metabolic acidosis, and….
Volume overload
• Sodium and intravascular volume balance are
usually maintained via homeostatic mechanisms
until the GFR falls below 10 to 15 mL/min.
• However, the patient with mild to moderate chronic
kidney disease, despite being in relative volume
balance, is less able to respond to rapid infusions of
sodium and is therefore prone to fluid overload.
• Patients with CKD and volume overload
generally respond to the combination
of dietary sodium restriction and
diuretic therapy.
• sodium intake may also help decrease
progression of chronic kidney disease
by lowering intraglomerular pressure
Hyperkalemia
• The ability to maintain potassium excretion at near
normal levels is generally maintained in patients with
renal disease as long as both aldosterone secretion
and distal flow are maintained
•
Thus, hyperkalemia generally develops in the
patient who is oliguric or who has an additional
problem such as a high potassium diet, increased
tissue breakdown, or hypoaldosteronism (due in
some cases to the administration of an ACE inhibitor
or ARB)
• In this setting, institution of a low-potassium diet or
concurrent use of a loop diuretic often ameliorates
the degree of hyperkalemia.
•
In selected patients, low dose Kayexalate (5 grams
with each meal) can be used to lower the serum
potassium concentration without the side effects
Metabolic acidosis
• There is an increasing tendency to
retain hydrogen ions among patients
with chronic renal disease
• This can lead to a progressive
metabolic acidosis with the serum
bicarbonate concentration tending to
stabilize between 12 and 20 meq/L, and
rarely falling below 10 meq/L
• There are three major reasons why treatment of the
acidemia may be desirable in patients with chronic
kidney disease.
• Bicarbonate supplementation may
progression of chronic kidney disease
slow
the
• Bone buffering of some of the excess hydrogen ions
is associated with the release of calcium and
phosphate from bone
• Uremic acidosis can increase skeletal muscle
breakdown and diminish albumin synthesis, leading
to loss of lean body mass and muscle weakness.
• alkali therapy to maintain the serum
bicarbonate concentration above 23
meq/L is recommended.
• If alkali is given, sodium bicarbonate (in
a daily dose of 0.5 to 1 meq/kg per day)
is the agent of choice
Hyperphosphatemia
• A tendency toward phosphate retention begins early
in renal disease, due to the reduction in the filtered
phosphate load.
• the hypersecretion of PTH is initially appropriate,
since PTH can correct both hyperphosphatemia and
hypocalcemia.
• The price paid is secondary HPT and development
of renal osteodystrophy
• Once the GFR falls below 25 to 30 mL/min, the
addition of oral phosphate binders are usually
required to prevent hyperphosphatemia
• The K/DOQI recommend that phosphorus levels
should be between 2.7 and 4.6 mg/dL among
patients with stage 3 and 4, and between 3.5 and 5.5
mg/dL among those with stage 5 disease
• The serum calcium-phosphorus product should also
be maintained at <55 mg2/dL2
• hormone levels begin to rise when the creatinine
clearance is less than 40 to 70 mL/min
•
Dietary phosphate restriction may limit the
development of secondary HPT in patients with
chronic kidney disease.( about 800 mg/day )
• The K/DOQI work group suggests the
following target serum levels for intact PTH ;
• 35 to 70 pg/mL for those with stage 3
disease
• 70 to 110 pg/mL for those with stage 4
disease
• 150 to 300 pg/mL for stage 5 disease
• In patients with stage 3 to 5 CKD, the K/DOQI
guidelines suggest that total elemental calcium
intake (including both dietary calcium intake and
calcium-based phosphate binders) should not
exceed 2,000 mg/day.
• Lanthanum, a rare earth element, also
has significant phosphate binding
properties. Although no significant
clinical adverse effects have yet been
reported, the long-term safety of
lanthanum, particularly its possible
effect on bone and other organs,
remains unclear.
• Most other phosphate binders should be avoided:
• Aluminum hydroxide, the previous standard,
because of the gradual induction of aluminum
toxicity
• Magnesium-containing antacids, because of the risk
of hypermagnesemia and the frequent development
of diarrhea
• Calcium citrate, since it markedly
intestinal aluminum absorption
increases
Hypertension
• Hypertension is present in approximately 80 to 85
percent of patients with CKD
• Treating hypertension can both slow the progression
of proteinuric CKD and reduce the rate of
cardiovascular complications.
• The desired degree of blood pressure control can
usually be safely achieved with combined therapy
which usually begins with an ACE inhibitor or ARB
and a diuretic.
• A loop diuretic is recommended for the treatment of
hypertension and edema in patients with chronic
kidney disease.
• The thiazide diuretic
in conventional dosage
become less effective as monotherapy when the
GFR falls below 20 mL/min. however, produce an
additive effect when administered with a loop
diuretic for refractory edema.
• The optimal blood pressure in hypertensive patients
with chronic kidney disease is uncertain
Anemia
•
The anemia of CKD is normocytic and
normochromic, and is due to reduced production of
EPO by the kidney and to shortened red cell survival
• anemia becoming
increasingly common as
glomerular filtration rates (GFRs) decline below 60
mL/min per 1.73 m2
• the evaluation of anemia in CKD should
begin when the Hgb level is less than
12 g/dL in females, and Hgb levels of
less than 13.5 g/dL in adult males
•
If untreated, the hematocrit of patients
with advanced chronic kidney disease
normally stabilizes at approximately 25
percent in the absence of bleeding or
hemolysis
• The anemia observed with chronic
kidney disease is largely diagnosed by
excluding non-renal causes of anemia
in the patient with a suitably decreased
GFR.
• Targeting Hgb levels in the range of 11
to 12 g/dL
• The EPO dose should be approximately
50 to 100 U/kg per week.
• An adequate response to EPO requires
the maintenance of sufficient iron
• K/DOQI guidelines defined low levels of
iron tests among patients with
predialysis CKD as either serum ferritin
<100 ng/mL or TSAT <20 percent
•
If oral iron is given, adults should
receive a daily dose of approximately
200 mg of elemental iron, usually as
ferrous sulfate 325 mg three times
daily (65 mg elemental iron per tablet).
Dyslipidemia
• Abnormal lipid metabolism is common in patients
with renal disease
•
The primary finding in chronic kidney disease is
hypertriglyceridemia with the total cholesterol
concentration usually being normal (perhaps due in
part to malnutrition in some patients).
• Patients with chronic kidney disease should be
assessed for dyslipidemia, including a total
cholesterol, LDL, HDL, and TG.
• Beneficial effects of statins on vessel
stiffening and endothelial function in
renal failure have been described
• anti-inflammatory role for statins in
patients without renal failure have been
described
• Effect on proteinuria
• statins may
progression
slow
the
rate
of
• may improve cardiovascular outcomes
• the goal LDL-cholesterol is similar to that in patients
with CHD, which has been less than 100 mg/dL or a
lower goal of less than 70 mg/dL
•
Limited data suggest that lipid lowering may have an
additional benefit which is slowing the rate of
progression of the underlying renal disease.
Treatment of complications of
ESRD
•
Once the patient has reached the stage of near endstage renal disease (GFR less than 15 mL/min),
signs and symptoms related to uremia begin to
occur, such as malnutrition, anorexia, nausea,
vomiting, fatigue, sexual dysfunction, platelet
dysfunction, pericarditis, and neuropathy.
Malnutrition
•
Malnutrition is common in patients
with advanced chronic renal disease
because of a lower food intake
(principally due to anorexia), decreased
intestinal absorption and digestion, and
metabolic acidosis
• It is therefore desirable to monitor the
nutritional status of patients with
chronic kidney disease.
• To best assess nutritional status, the serum albumin
concentration and body weight should be measured
serially
•
these should be measured approximately every one to
three months for those with estimated GFRs <20
mL/min, and more frequently if necessary for those
with GFRs ≤15 mL/min
Uremic bleeding
•
An increased tendency to bleeding is present in both
acute and chronic kidney disease. This appears to
correlate most closely with prolongation of the bleeding
time, due primarily to impaired platelet function.
• No specific therapy is required in asymptomatic
patients. However, correction of the platelet dysfunction
is desirable in patients who are actively bleeding or who
are about to undergo a surgical or invasive procedure
(such as a renal biopsy).
• A number of different modalities can be used in this
setting….
Pericarditis
• Fever, pleuritic chest pain, and a pericardial friction
rub are the major presentations
•
One relatively characteristic feature of uremic
pericarditis is that the ECG does not usually show
the typical diffuse ST and T wave elevation,
presumably because this is a metabolic pericarditis
and epicardial injury is uncommon.
• The occurrence of pericarditis in a patient with mild
to moderate chronic kidney disease is another clue
that the renal disease is probably not responsible.
Uremic neuropathy
• Dysfunction of the central and peripheral nervous
system, including encephalopathy, polyneuropathy,
and mononeuropathy are important complications of
end-stage renal disease.
• Sensory dysfunction, characterized by the restless
leg, are frequent presentations of uremic neuropathy.
• These complications are usually absolute indications
for the initiation of dialysis.
PREPARATION FOR AND
INITIATION OF RENAL
REPLACEMENT THERAPY
Referral to nephrologists
•
Patients with CKD should be referred
to a nephrologist early in the course of
their disease, preferably before the
plasma
creatinine
concentration
exceeds 1.2 and 1.5 mg/dL in women
and men, respectively, or the eGFR is
less than 60 mL/min per 1.73 m2.
•
It is important to identify patients who may
eventually require RRT since adequate preparation
can decrease morbidity and perhaps mortality.
•
Early identification enables dialysis to be initiated at
the optimal time with a functioning chronic access
and may also permit the recruitment and evaluation
of family members for the placement of a renal
allograft prior to the need for dialysis.
• Protective therapy has the greatest impact if it is
initiated before the plasma creatinine concentration
exceeds 1.2 and 1.5 mg/dL in women and men,
respectively, or the eGFR is less than 60 mL/min per
1.73m2. At this point, most patients have already lost
more than one-half of their GFR.
Choice of renal replacement
therapy
•
Once it is determined that RRT will eventually be
required, the patient should be counseled to consider
the advantages and disadvantages of hemodialysis
(in-center or at home), peritoneal dialysis (continuous
or intermittent modalities), and renal transplantation
(living or deceased donor)
• The 2006 K/DOQI guidelines recommend that patients
with a GFR less than 30 mL/min per 1.73 m2 should be
educated concerning these issues
• Kidney transplantation is the treatment
of choice for end-stage renal disease. A
successful kidney transplant improves
the quality of life and reduces the
mortality risk
• Referral to a transplant program should
occur once renal replacement therapy
is thought to be required within the next
year
• patients should be referred for surgery
to attempt access construction when it
is estimated that the patient is within
one year of the anticipated need for
dialysis as manifested by a GFR less
than 25 mL/min, a plasma creatinine
concentration greater than 4 mg/mL, or
a rapid rate of progression.
• The 2006 K/DOQI guidelines
recommend that a synthetic
graft be placed at least three to
six
weeks
prior
to
the
anticipated
start
of
hemodialysis
• Preparation for peritoneal dialysis ;
•
Peritoneal dialysis catheters, which are placed into
the abdominal cavity, can be used immediately after
placement. However, to minimize the risk of fluid
leak, it is preferable to wait at least 10 to 14 days
before beginning dialysis.
• If dialysis is required less than 10 days following
catheter placement, small volume exchanges
performed in the recumbent position can be
performed with little risk of leak
Indications for renal
replacement therapy
•
The decision to initiate dialysis in a
patient with chronic kidney disease
involves the consideration of subjective
and objective parameters by the
physician and the patient.
• Pericarditis or pleuritis (urgent indication)
• Progressive uremic encephalopathy or neuropathy, with
signs such as confusion, asterixis, myoclonus, wrist or
foot drop, or, in severe, cases, seizures (urgent
indication)
• A clinically significant bleeding diathesis attributable to
uremia (urgent indication)
• Fluid overload refractory to diuretics
• Hypertension poorly responsive to antihypertensive
medications
• Persistent metabolic disturbances that are refractory to
medical therapy. These include hyperkalemia, metabolic
acidosis,
hypercalcemia,
hypocalcemia,
and
hyperphosphatemia.
• Persistent nausea and vomiting
• Weight loss or signs of malnutrition
Thanks for your attention