chronic kidney disease

1. CHRONIC KIDNEY DISEASE(CKD)
Dr. Abdulkadir SAĞDIÇ
SOMALIA MOGADISHU
25.01.2018

2. CKD
 The guidelines define CKD as either kidney
damage or a decreased glomerular filtration
rate (GFR) of less than 60 mL/min/1.73
m2 for at least 3 months. Whatever the
underlying etiology, once the loss of
nephrons and reduction of functional renal
mass reaches a certain point, the remaining
nephrons begin a process of irreversible
sclerosis that leads to a progressive decline
in the GFR

3. RENAL FUNCTION FORMULAS
 The Cockcroft-Gault formula for estimating
creatinine clearance (CrCl) should be used
routinely as a simple means to provide a
reliable approximation of residual renal
function in all patients with CKD. The
formulas are as follows:
 CrCl (male) = ([140-age] × weight in
kg)/(serum creatinine × 72)
 CrCl (female) = CrCl (male) × 0.85

5.  the Modification of Diet in Renal Disease
(MDRD) Study equationcould be used to
calculate the glomerular filtration rate (GFR).
This equation does not require a patient's
weight.
 However, the MDRD underestimates the
measured GFR at levels above 60
mL/min/1.73 m

6.  the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) equation is more
accurate than the MDRD Study equation
overall and across most subgroups and that
it can report estimated GFRs that are at or
above 60 mL/min/1.73 m2

7. CKD STAGING
 Stage 1: Kidney damage with normal or increased GFR
(>90 mL/min/1.73 m 2)
 Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m 2)
 Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73
m 2)
 Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73
m 2)
 Stage 4: Severe reduction in GFR (15-29 mL/min/1.73
m 2)
 Stage 5: Kidney failure (GFR <15 mL/min/1.73 m 2 or
dialysis)

8.  In stage 1 and stage 2 CKD, reduced GFR alone does not
clinch the diagnosis, because the GFR may in fact be
normal or borderline normal. In such cases, the presence
of one or more of the following markers of kidney damage
can establish the diagnosis :
 Albuminuria (albumin excretion >30 mg/24 hr or
albumin:creatinine ratio >30 mg/g [>3 mg/mmol])
 Urine sediment abnormalities
 Electrolyte and other abnormalities due to tubular
disorders
 Histologic abnormalities
 Structural abnormalities detected by imaging
 History of kidney transplantation in such cases

9. CKD
 In an update of its CKD classification system, advised
that GFR and albuminuria levels be used together,
rather than separately, to improve prognostic
accuracy in the assessment of CKD.
 More specifically, the guidelines recommended the
inclusion of estimated GFR and albuminuria levels
when evaluating risks for overall mortality,
cardiovascular disease, end-stage kidney failure,
acute kidney injury, and the progression of CKD.
 Referral to a kidney specialist was recommended for
patients with a very low GFR (<15 mL/min/1.73 m²) or
very high albuminuria (>300 mg/24 h).

10. “””” EPIDEMIOLOGY
 Kidney disease is the ninth leading cause of
death in the United States.
 The US prevalence of CKD increases
dramatically with age (4% at age 29-39 y; 47%
at age >70 y), with the most rapid growth in
people aged 60 years or older.
 A systematic review and meta-analysis of
observational studies estimating CKD
prevalence in general populations worldwide
found a consistent estimated global CKD
prevalence of 11-13%. The majority of cases are
stage 3.

11.  Although CKD affects all races, the incidence
rate of ESRD among blacks in the United States
is nearly 4 times that for whites.
 Choi et al found that rates of ESRD among
black patients exceeded those among white
patients at all levels of baseline estimated
glomerular filtration rate (GFR).
 Risk of ESRD among black patients was highest
at an estimated GFR of 45-59 mL/min/1.73 m2,
as was the risk of mortality.

12.  Schold et al found that among black kidney transplant
recipients, rates of graft loss and acute rejection were
higher than in white recipients, especially among
younger patients.
 Hicks et al looked at the connection between black
patients with the sickle cell trait and their increased
risk for kidney disease; the study found that sickle cell
trait was not associated with diabetic or nondiabetic
ESRD in a large sample of black patients.
 Glomerular disease was much more common among
nonwhite persons.

13.  Overall, FSGS in particular is more common among
Hispanic Americans and black persons, as is the risk
of nephropathy with diabetes or with hypertension; in
contrast, IgA nephropathy is rare in black individuals
and more common among those with Asian ancestry.
 CKD in children is somewhat more common in boys,
because posterior urethral valves, the most common
birth defect leading to CKD, occur only in boys.
Importantly, many individuals with congenital kidney
disease such as dysplasia or hypoplasia do not
clinically manifest CKD or ESRD until adulthood.

14. ETIOLOGY
 Diabetic kidney disease
 Hypertension
 Vascular disease
 Glomerular disease (primary or secondary)
 Cystic kidney diseases
 Tubulointerstitial disease
 Urinary tract obstruction or dysfunction
 Recurrent kidney stone disease
 Congenital (birth) defects of the kidney or bladder
 Unrecovered acute kidney injury

15. Vascular diseases that can cause CKD include the
following:
 Renal artery stenosis
 Cytoplasmic pattern antineutrophil cytoplasmic
antibody
(C-ANCA)–positive and perinuclear pattern
antineutrophil cytoplasmic antibody (P-ANCA)–
positive vasculitides
 ANCA-negative vasculitides
 Atheroemboli
 Hypertensive nephrosclerosis
 Renal vein thrombosis

16. Primary glomerular diseases include the following:
 Membranous nephropathy
 Alport syndrome
 Immunoglobulin A (IgA) nephropathy
 Focal and segmental glomerulosclerosis (FSGS)
 Minimal change disease
 Membranoproliferative glomerulonephritis (MPGN)
 Complement-related diseases (eg, atypical hemolytic-
uremic syndrome [HUS], dense deposit disease)
 Rapidly progressive (crescentic) glomerulonephritis

17. Secondary causes of glomerular disease include the following:
 Diabetes mellitus Systemic lupus erythematosus Rheumatoid
arthritis Mixed connective tissue disease
 Scleroderma Wegener granulomatosis Mixed
cryoglobulinemia Endocarditis
 Hepatitis B and C Syphilis Human immunodeficiency virus
(HIV) Parasitic infection
 Heroin use Gold Penicillamine Amyloidosis Light-chain
deposition disease
 Neoplasia Thrombotic thrombocytopenic purpura (TTP)
 Shiga-toxin or Streptococcus pneumoniae – related HUS
Henoch-Schönlein purpura
 Reflux nephropathy

18. Causes of tubulointerstitial disease include the following:
 Drugs (eg, sulfonamides, allopurinol)
 Infection (viral, bacterial, parasitic)
 Sjögren syndrome
 Tubulointerstitial nephritis and uveitis (TINU) syndrome
 Chronic hypokalemia
 Chronic hypercalcemia
 Sarcoidosis
 Multiple myeloma cast nephropathy
 Heavy metals
 Radiation nephritis
 Polycystic kidneys
 Cystinosis and other inherited diseases

19. Urinary tract obstruction may result from any of
the following:
 Benign prostatic hypertrophy
 Urolithiasis (kidney stones)
 Urethral stricture
 Tumors
 Neurogenic bladder
 Congenital (birth) defects of the kidney or
bladder
 Retroperitoneal fibrosis

20. SIGNS AND SYMPTOMS
 Patients with CKD stages 1-3 are generally
asymptomatic.
 Typically, it is not until stages 4-5
(GFR <30 mL/min/1.73 m²) that endocrine/metabolic
derangements or disturbances in water or electrolyte
balance become clinically manifest.
 Signs of metabolic acidosis in stage 5 CKD include
the following:
 Protein-energy malnutrition
 Loss of lean body mass
 Muscle weakness

21. SIGNS AND SYMPTOMS
 Signs of alterations in the way the kidneys
are handling salt and water in stage 5 include
the following:
 Peripheral edema
 Pulmonary edema
 Hypertension

22. SIGNS AND SYMPTOMS
Anemia in CKD is associated with the following:
 Fatigue
 Reduced exercise capacity
 Impaired cognitive and immune function
 Reduced quality of life
 Development of cardiovascular disease
 New onset of heart failure or the development of
more severe heart failure
 Increased cardiovascular mortality

23. SIGNS AND SYMPTOMS
 Pericarditis: Can be complicated by cardiac tamponade, possibly
resulting in death if unrecognized
 Encephalopathy: Can progress to coma and death
 Peripheral neuropathy, usually asymptomatic
 Restless leg syndrome
 Gastrointestinal symptoms: Anorexia, nausea, vomiting, diarrhea
 Skin manifestations: Dry skin, pruritus, ecchymosis
 Fatigue, increased somnolence, failure to thrive
 Malnutrition
 Erectile dysfunction, decreased libido, amenorrhea
 Platelet dysfunction with tendency to bleed

24. SIGNS AND SYMPTOMS
 Screen adult patients with CKD for
depressive symptoms; self-report scales at
initiation of dialysis therapy reveal that 45%
of these patients have such symptoms, albeit
with a somatic emphasis.

25. DIAGNOSIS
LABORATORY STUDIES
 Complete blood count (CBC)
 Basic metabolic panel
 Urinalysis
 Serum albumin levels: Patients may have
hypoalbuminemia due to malnutrition, urinary
protein loss, or chronic inflammation
 Lipid profile: Patients with CKD have an
increased risk of cardiovascular disease

26. DIAGNOSIS
Evidence of renal bone disease can be
derived from the following tests:
 Serum calcium and phosphate
 25-hydroxyvitamin D
 Alkaline phosphatase
 Intact parathyroid hormone (PTH) levels

27. DIAGNOSIS
 Serum and urine protein electrophoresis and
free light chains: Screen for a monoclonal
protein possibly representing multiple
myeloma
 Antinuclear antibodies (ANA), double-
stranded DNA antibody levels: Screen for
systemic lupus erythematosus
 Serum complement levels: Results may be
depressed with some glomerulonephritides

28.  Cytoplasmic and perinuclear pattern antineutrophil
cytoplasmic antibody (C-ANCA and P-ANCA) levels:
Positive findings are helpful in the diagnosis of
granulomatosis with polyangiitis (Wegener granulomatosis);
P-ANCA is also helpful in the diagnosis of microscopic
polyangiitis
 Anti–glomerular basement membrane (anti-GBM)
antibodies: Presence is highly suggestive of underlying
Goodpasture syndrome
 Hepatitis B and C, human immunodeficiency virus (HIV),
Venereal Disease Research Laboratory (VDRL) serology:
Conditions associated with some glomerulonephritides

29. DIAGNOSIS
IMAGING STUDIES
 Renal ultrasonography: Useful to screen for
hydronephrosis, which may not be observed in
early obstruction or dehydrated patients; or for
involvement of the retroperitoneum with fibrosis,
tumor, or diffuse adenopathy; small, echogenic
kidneys are observed in advanced renal failure
 Retrograde pyelography: Useful in cases with
high suspicion for obstruction despite negative
renal ultrasonograms, as well as for diagnosing
renal stones

30. DIAGNOSIS
 Computed tomography (CT) scanning: Useful to
better define renal masses and cysts usually noted
on ultrasonograms; also the most sensitive test for
identifying renal stones
 Magnetic resonance imaging (MRI): Useful in patients
who require a CT scan but who cannot receive
intravenous contrast; reliable in the diagnosis of renal
vein thrombosis
 Renal radionuclide scanning: Useful to screen for
renal artery stenosis when performed with captopril
administration; also quantitates the renal contribution
to the GFR

31. DIAGNOSIS
BIOPSY
 Percutaneous renal biopsy is generally
indicated when renal impairment and/or
proteinuria approaching the nephrotic range
are present and the diagnosis is unclear after
appropriate workup.

32. PATHOPHYSIOLOGY
 A normal kidney contains approximately 1 million
nephrons, each of which contributes to the total
glomerular filtration rate (GFR).
 In the face of renal injury (regardless of the etiology), the
kidney has an innate ability to maintain GFR, despite
progressive destruction of nephrons, as the remaining
healthy nephrons manifest hyperfiltration and
compensatory hypertrophy.
 This nephron adaptability allows for continued normal
clearance of plasma solutes.
 Plasma levels of substances such as urea and creatinine
start to show measurable increases only after total GFR
has decreased to 50%.

33. PATHOPHYSIOLOGY
 The plasma creatinine value will
approximately double with a 50% reduction
in GFR. For example, a rise in plasma
creatinine from a baseline value of 0.6 mg/dL
to 1.2 mg/dL in a patient, although still within
the adult reference range, actually
represents a loss of 50% of functioning
nephron mass.

34. PATHOPHYSIOLOGY
 The hyperfiltration and hypertrophy of residual
nephrons, although beneficial for the reasons
noted, has been hypothesized to represent a
major cause of progressive renal dysfunction.
The increased glomerular capillary pressure
may damage the capillaries, leading initially to
secondary focal and segmental
glomerulosclerosis (FSGS) and eventually to
global glomerulosclerosis. This hypothesis is
supported by studies of five-sixths
nephrectomized rats, which develop lesions
identical to those observed in humans with
chronic kidney disease (CKD).

35. PATHOPHYSIOLOGY
 Factors other than the underlying disease process and glomerular
hypertension that may cause progressive renal injury include the
following:
 Systemic hypertension
 Nephrotoxins (eg, nonsteroidal anti-inflammatory drugs [NSAIDs],
intravenous contrast media)
 Decreased perfusion (eg, from severe dehydration or episodes of
shock)
 Proteinuria (in addition to being a marker of CKD)
 Hyperlipidemia
 Hyperphosphatemia with calcium phosphate deposition
 Smoking
 Uncontrolled diabetes

36. PATHOPHYSIOLOGY
 Hyperkalemia usually does not develop until
the GFR falls to less than 20-25 mL/min/1.73
m², at which point the kidneys have
decreased ability to excrete potassium.
 Hyperkalemia in CKD can be aggravated by
an extracellular shift of potassium, such as
occurs in the setting of acidemia or from lack
of insulin.

37. PATHOPHYSIOLOGY
 In CKD, the kidneys are unable to produce
enough ammonia in the proximal tubules to
excrete the endogenous acid into the urine in
the form of ammonium. In stage 5 CKD,
accumulation of phosphates, sulfates, and
other organic anions are the cause of the
increase in anion gap.

38. PATHOPHYSIOLOGY
Metabolic acidosis has been shown to have
deleterious effects on protein balance,
leading to the following:
 Negative nitrogen balance
 Increased protein degradation
 Increased essential amino acid oxidation
 Reduced albumin synthesis
 Lack of adaptation to a low-protein diet

39. PATHOPHYSIOLOGY
 Metabolic acidosis also leads to an increase in
fibrosis and rapid progression of kidney disease,
by causing an increase in ammoniagenesis to
enhance hydrogen excretion.
 Metabolic acidosis is a factor in the
development of renal osteodystrophy, because
bone acts as a buffer for excess acid, with
resultant loss of mineral. Acidosis may interfere
with vitamin D metabolism, and patients who
are persistently more acidotic are more likely to
have osteomalacia or low-turnover bone
disease.

40. PATHOPHYSIOLOGY
 As kidney function declines further, sodium retention
and extracellular volume expansion lead to peripheral
edema and, commonly, pulmonary edema and
hypertension.
 Tubulointerstitial renal diseases represent the
minority of cases of CKD. However, it is important to
note that such diseases often cause fluid loss rather
than overload.
 Thus, despite moderate or severe reductions in GFR,
tubulointerstitial renal diseases may manifest first as
polyuria and volume depletion, with inability to
concentrate the urine.

41.  No reticulocyte response occurs. RBC survival is
decreased, and bleeding tendency is increased from
the uremia-induced platelet dysfunction. Other
causes of anemia in CKD include the following:
 Chronic blood loss: Uremia-induced platelet
dysfunction enhances bleeding tendency
 Secondary hyperparathyroidism
 Inflammation
 Nutritional deficiency
 Accumulation of inhibitors of erythropoiesis

42. Different types of bone disease occur with CKD,
as follows:
 High-turnover bone disease from high
parathyroid hormone (PTH) levels
 Low-turnover bone disease (adynamic bone
disease)
 Defective mineralization (osteomalacia)
 Mixed disease
 Beta-2-microglobulin–associated bone disease

43.  Bone disease in children is similar but occurs
during growth. Therefore, children with CKD
are at risk for short stature, bone curvature,
and poor mineralization (“renal rickets” is the
equivalent term for adult osteomalacia).

44. Secondary hyperparathyroidism develops in CKD
because of the following factors:
 Hyperphosphatemia
 Hypocalcemia
 Decreased renal synthesis of 1,25-
dihydroxycholecalciferol (1,25-dihydroxyvitamin D, or
calcitriol)
 Intrinsic alteration in the parathyroid glands, which gives
rise to increased PTH secretion and increased
parathyroid growth
 Skeletal resistance to PTH
Calcium and calcitriol are primary feedback inhibitors;
hyperphosphatemia is a stimulus to PTH synthesis and
secretion.

45.  Phosphate retention begins in early CKD; when the
GFR falls, less phosphate is filtered and excreted, but
because of increased PTH secretion, which increases
renal excretion, serum levels do not rise initially. As
the GFR falls toward CKD stages 4-5,
hyperphosphatemia develops from the inability of the
kidneys to excrete the excess dietary intake.
 Hyperphosphatemia suppresses the renal
hydroxylation of inactive 25-hydroxyvitamin D to
calcitriol, so serum calcitriol levels are low when the
GFR is less than 30 mL/min/1.73 m². Increased
phosphate concentration also effects PTH
concentration by its direct effect on the parathyroid
glands (posttranscriptional effect).

46.  Hypocalcemia develops primarily from
decreased intestinal calcium absorption
because of low plasma calcitriol levels. It
also possibly results from increased calcium-
phosphate binding, caused by elevated
serum phosphate levels.

48.  Low serum calcitriol levels, hypocalcemia, and
hyperphosphatemia have all been demonstrated
to independently trigger PTH synthesis and
secretion. As these stimuli persist in CKD,
particularly in the more advanced stages, PTH
secretion becomes maladaptive, and the
parathyroid glands, which initially hypertrophy,
become hyperplastic. The persistently elevated
PTH levels exacerbate hyperphosphatemia from
bone resorption of phosphate.

50.  If serum levels of PTH remain elevated, a high ̶ bone
turnover lesion, known as osteitis fibrosa, develops.
This is one of several bone lesions, which as a group
are commonly known as renal osteodystrophy and
which develop in patients with severe CKD. Osteitis
fibrosa is common in patients with ESRD.
 The pathogenesis of adynamic bone disease is not
well defined, but several factors may contribute,
including high calcium load, use of vitamin D sterols,
increasing age, previous corticosteroid therapy,
peritoneal dialysis, and increased level of N-
terminally truncated PTH fragments.

53.  Low-turnover osteomalacia in the setting of
CKD is associated with aluminum accumulation.
It is markedly less common than high-turnover
bone disease.
 Another form of bone disease is dialysis-related
amyloidosis, which is now uncommon in the era
of improved dialysis membranes. This condition
occurs from beta-2-microglobulin accumulation
in patients who have required chronic dialysis
for at least 8-10 years. It manifests with cysts at
the ends of long bones.

54. MANAGEMENT
 Anemia: When the hemoglobin level is below 10 g/dL, treat with
erythropoiesis-stimulating agents (ESAs), which include epoetin
alfa and darbepoetin alfa after iron saturation and ferritin levels
are at acceptable levels
 Hyperphosphatemia: Treat with dietary phosphate binders and
dietary phosphate restriction
 Hypocalcemia: Treat with calcium supplements with or without
calcitriol
 Hyperparathyroidism: Treat with calcitriol or vitamin D analogues
or calcimimetics
 Volume overload: Treat with loop diuretics or ultrafiltration
 Metabolic acidosis: Treat with oral alkali supplementation
 Uremic manifestations: Treat with long-term renal replacement
therapy (hemodialysis, peritoneal dialysis, or renal
transplantation)

55. MANAGEMENT
Indications for renal replacement therapy include the following:
 Severe metabolic acidosis
 Hyperkalemia
 Pericarditis
 Encephalopathy
 Intractable volume overload
 Failure to thrive and malnutrition
 Peripheral neuropathy
 Intractable gastrointestinal symptoms
 In asymptomatic patients,
a GFR of 5-9 mL/min/1.73 m², irrespective of the cause of the
CKD or the presence or absence of other comorbidities

56. PROGNOSIS
 Timely initiation of chronic renal replacement
therapy is imperative to prevent the uremic
complications of CKD that can lead to significant
morbidity and death.
 Tangri et al ; reported that lower estimated
glomerular filtration rate (GFR), higher
albuminuria, younger age, and male sex pointed
to a faster progression of kidney failure. Also, a
lower serum albumin, calcium, and bicarbonate
level and a higher serum phosphate level were
found to predict an elevated risk of kidney
failure.

57.  Rates of hospitalization in the CKD popu-
lation, reflecting its total disease burden, are
3-5 times higher than those of patients
without CKD.
 Rates of hospitalization for cardiovascular
disease and bacterial infection are
particularly elevated.

58. MORTALITY
 Mortality in patients with CKD in 2009 was 56%
greater than that in patients without CKD.
 For patients with stages 4-5 CKD, the adjusted
mortality rate is 76% greater.
 The highest mortality rate is within the first 6 months
of initiating dialysis.
 Mortality then tends to improve over the next 6
months, before increasing gradually over the next 4
years.
 The 5-year survival rate for a patient undergoing
long-term dialysis in the United States is
approximately 35%, and approximately 25% in
patients with diabetes.

59.  At every age, patients with ESRD on dialysis
have significantly increased mortality when
compared with nondialysis patients and
individuals without kidney disease.
 The life expectancy of a patient aged 60 years
who is starting hemodialysis is closer to 4 years.
 Among patients aged 65 years or older who
have ESRD, mortality rates are 6 times higher
than in the general population.

60.  The most common cause of sudden death in patients with
ESRD is hyperkalemia, which often follows missed
dialysis or dietary indiscretion.
 The most common cause of death overall in the dialysis
population is cardiovascular disease; cardiovascular
mortality is 10-20 times higher in dialysis patients than in
the general population.
 Hypoalbuminemia (a marker of protein-energy
malnutrition and a powerful predictive marker of mortality
in dialysis patients, as well as in the general population)
was independently associated with low bicarbonate, as
well as with the inflammatory marker C-reactive protein.

61.  A study by Navaneethan et al found a connection
between low levels of 25-hydroxyvitamin D (25[OH]D) and
all-cause mortality in patients with nondialysis
CKD. Adjusted risk of mortality was 33% higher in patients
whose 25(OH)D levels were below 15 ng/mL.
 Puberty is often delayed among males and females with
significant CKD.
 Female patients with advanced CKD commonly develop
menstrual irregularities.
 Women with ESRD are typically amenorrheic and infertile.
 In advanced CKD and ESRD, pregnancy is associated
with markedly decreased fetal survival.

62.  Many patients with CKD have low circulating
levels of 25(OH)D.
 A study of 1099 patients (mostly men) with
advanced CKD found that the lowest tertile of
1,25(OH)(2)D (< 15 pg/mL) was associated with
death
 A retrospective cohort study in 12,763 non–
dialysis-dependent patients with CKD found that
25(OH)D levels below 15 ng/mL were
associated independently with all-cause
mortality.

63.  Both iron and erythropoietin treatments
commonly prescribed in patients with chronic
kidney disease cause a significant decrease in
HbA1c without affecting blood glucose levels
 Metformin is contraindicated in patients with
impaired renal function, as indicated by a serum
creatinine level of greater than 1.5 mg/dL in men
or of more than 1.4 mg/dL in women, or an
estimated GFR of less than 60 mL/min. It also
should not be used within 48 hours of IV
iodinated contrast medium

64. PATIENT EDUCATION
 Importance of avoiding factors leading to increased
progression
 Natural disease progression
 Prescribed medications (highlighting their potential
benefits and adverse effects)
 Avoidance of nephrotoxins
 Diet
 Renal replacement modalities, including peritoneal
dialysis, hemodialysis, and transplantation
 Timely placement of vascular access for hemodialysis

65.  Women of childbearing age who have end-stage
renal disease (ESRD) should be counseled that
although their fertility is greatly reduced,
 Pregnancy can occur and is associated with
higher risk than in women who do not have
renal disease.
 Many medications used to treat CKD are
potentially teratogenic; in particular, women
taking angiotensin-converting enzyme (ACE)
inhibitors and certain immunosuppressive
treatments require clear counseling.