CHRONIC KIDNEY DISEASE:

Causes and Manifestations

Vimar A. Luz, MD, FPCP, DPSN

DEFINITIONS

Chronic renal disease (CRD) is a pathophysiologic

process (last more than 3 months) with multiple
etiologies, resulting in the inexorable attrition of nephron
number and function, and frequently leading to end-
stage renal disease (ESRD).

ESRD represents a clinical state or condition in which

there has been an irreversible loss of endogenous renal
function, of a degree sufficient to render the patient
permanently dependent upon renal replacement therapy
(dialysis or transplantation) in order to avoid life-
threatening uremia.
DEFINITIONS

Azotemia- refers to the retention of nitrogenous waste

products as renal insufficiency develops

Uremia- is the clinical and laboratory syndrome,

reflecting dysfunction of all organ systems as a result of
untreated or undertreated acute or chronic renal failure.
Definition Of Chronic Kidney Disease (CKD)

GFR <60 mL/min/1.73m2 for ≥3 months,

and/or
Kidney damage for ≥3 months
Identifying kidney damage
Proteinuria
Urine sediment abnormalities
Imaging tests
Abnormalities in blood or urine composition
Biopsy

NKF. Am J Kidney Dis 2004; 43(5 Suppl 1):S65

ESTIMATION OF GFR

Cockcroft-Gault formula

MEN Ccr=(140-age) (weight in kg) or 1.23 (140-age)(wt)

72 x Pcr (mg/dl) Pcr (umol/L)

WOMEN Ccr= (140-age) (wt) or 1.04 (140-age)(wt)

85 x Pcr(mg/dl) Pcr (umol/L)

*overestimates Ccr in obese pts and those on low protein diet

Determine chronicity of the disease
– History

– Renal biopsy- predominance of glomerulosclerosis or interstitial

fibrosis

– Renal ultrasound to measure kidney size

Small kidneys (<9cm)
Chronic disease with normal size kidneys
– Diabetic nephropathy
– HIV-assd nephropathy
– Infiltrative diseases ( myeloma kidney)
 Prevalence Of CKD
In US Population (Age > 20 Years)

% of Relevant
Stage Description GFR (mL/min/1.73m ) 2
Number of People Population

Kidney damage with normal

1 ≥ 90 5,900,000 3.3
or ↑ GFR

Kidney damage with mild ↓

2 60-89 5,300,000 3.0
GFR

3 Moderate ↓ GFR 30-59 7,600,000 4.3

4 Severe ↓ GFR 15-29 400,000 0.2

< 15
5 Kidney failure 300,000 0.1
(or dialysis)

19,500,000 10.9%

NKF-K/DOQI. Am J Kidney Dis.

Dis. 2001;37(suppl 1):S1-S238.
 NNHeS 2003-2004 Renal Report
Prevalence of CKD in Filipino adults using
predicted GFR from MDRD equation

Stages of GFR

1 > =90 72.8%

2 60-89 24.6%
3 30-59 2.2%
4 15-29 0.2%
5 <15 0.2%
The prevalence of CKD Stage 3 - 5 is 2.6%
Approximately 1,212,306 adult Filipinos
National Statistics Office

Kidney disease
is now # 10
cause of mortality
in the Philippines
 Stages in Progression of Chronic Kidney
Disease and Therapeutic Strategies
Complications

Increased Kidney CKD

Normal Damage ↓ GFR
risk failure death

Screening CKD risk Diagnosis Estimate Replacement

for CKD reduction; & treatment;progression;
by dialysis
risk Screening for Treat Treat & transplant
factors: CKD co-morbid complications;
diabetes conditions; Prepare for
hypertensi Slow replacement
on progression
age >60
family
history
US ethnic
minorities
6 Mechanisms of Renal Disease Progression
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN

then ↑ single nephron GFR
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN then

↑ single nephron GFR
Protein leak increasing Angiotension II
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN then

↑ single nephron GFR
Protein leak increasing Angiotension II
Downstream cytokine bath
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN then

↑ single nephron GFR
Protein leak increasing Angiotension II
Downstream cytokine bath
Neutrophils then macrophages, T
lymphocytes leading to interstitial nephritis
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN then

↑ single nephron GFR
Protein leak increasing Angiotension II
Downstream cytokine bath
Neutrophils then macrophages, T lymphocytes
leading to interstitial nephritis
Tubular epithelium responds by detaching
from their basement membrane forming new
interstitial fibroblasts
6 Mechanisms of Renal Disease Progression

Persistent glomerular injury leading to HTN then ↑ single

nephron GFR
Protein leak increasing Angiotension II
Downstream cytokine bath
Neutrophils then macrophages, T lymphocytes leading to
interstitial nephritis
Tubular epithelium responds by detaching from their
basement membrane forming new interstitial fibroblasts
Surviving fibroblasts lay down collagenous matrix
disrupting adjacent tubules and surrounding vessels
leaving an acellular scar
RISK FACTORS FOR CRD

family hx of heritable renal disease, HPN, DM, autoimmune disease

older age
past episode of acute renal failure
current evidence of kidney damage even with normal or increased
GFR
– proteinuria
– abnormal urinary sediment
– urinary tract structural abnormalities ( VUR)

Normal annual mean decline in GFR- begins at age 20 to 30 years=

1ml/min per 1.73m2
- mean GFR at age 70 is 70ml/min
CAUSES OF CKD

COMMON
– Diabetic nephropathy
– Glomerulonephritis
– Interstitial nephritis (including pyelopnephritis)
– Hypertension/vascular
– Hereditary/congenital disease
– Neoplasms
CAUSES OF CKD

LESS COMMON
– Metabolic
Cystinosis
Oxalosis
Nephrocalcinosis
Cystinuria
hyperuricemia
– Vascular
Ischemic renal disease
Scleroderma
Hemolytic uremic syndrome
Postpartum renal failure
– Dysproteinemias
Amyloid
Myeloma
Cryoglobulinemia
Light chain deposition disease
CAUSES OF CKD
LESS COMMON
– Hereditary
Alport syndrome
Fabry disease
Tuberous sclerosis
Sickle cell disease
– Vasculitis
Wegener’s granulomatosis
Microscopic polyangitis
Polyarteritis nodosa
lupus
– Malignancy
Renal cell carcinoma
lymphoma
– Structural
Cystic kidney disease other than adult-onset cystic
Congenital and acquired abn of the urinary tract e.g spina bifida,spinal cord
injury
Stage 1 and 2- usually asymptomatic

Stage 3 and 4-
Anemia
Loss of energy
Anorexia
Malnutrition
Abn in Ca and Ph metabolism
Abn in Na, water, K acid-base homeostasis

Stage 5-
Severe disturbances in activities of daily living, sense of
well being, nutrition,water and electrolyte
homeostasis-----UREMIA
MANIFESTATIONS
Neurologic
– Central
Daytime drowsiness and a tendency to sleep, which
progresses to increasing obtundation and, eventually,
coma
Decreased attentiveness and performance of cognitive tasks
Imprecise memory
Slurred speech
Asterixis and myoclonus
Seizures
Disorientation and confusion
– Peripheral
Sensorimotor peripheral neuropathy, often with burning
dysesthesia
Singultus (hiccup)
Restless leg syndrome
Increased muscle fatigability and muscle cramps
MANIFESTATIONS
Cardiovascular
Accelerated atherosclerosis
Cardiomyopathy
Pericarditis

Pulmonary
Atypical pulmonary edema
Pneumonitis
Fibrinous pleuritis
Gastrointestinal
Anorexia progressing to nausea and vomiting
Stomatitis and gingivitis
Parotitis
Peptic ulcer diathesis
Gastritis and duodenitis
Enterocolitis
Pancreatitis
Ascites
Dermatologic
Pruritus
Dystrophic calcification
Changes in skin pigmentation
Hematologic
Anemia
Altered neutrophilic chemotaxis
Depressed lymphocyte function
Bleeding diathesis with platelet dysfunction
Endocrinologic
Secondary hyperparathyrodism
Carbohydrate intolerance due to insulin resistance
Type IV hyperlipidemia
Altered peripheral thyroxine metabolism
Testicular atrophy
Ovarian dysfunction with amenorrhea, dysmenorrhea, dysfunctional
uterine bleeding, cystic ovarian disease
Ophthalmic
Conjunctival or cornel calcifications
PHYSICAL EXAMINATION

Abdominal masses (PKD)

Diminished pulses (atherosclerotic peripheral vascular
diseases)
Abnormal bruit ( renovascular disease)
Pallor
Excoriations (uremic pruritus)
Muscle wasting
Uremic breath
hypertension
LABORATORY FINDINGS

Elevated BUN, creatinine

Anemia
Hyperphosphatemia
Proteinuria
Hypoalbuminemia
Hypercholesterolemia
hyperuricemia
Hyperkalemia
Hyponatremia
Metabolic acidosis
FLUIDS, ELECTROLYTES AND ACID-BASE
DISORDERS

ECF VOLUME EXPANSION

HYPONATREMIA
HYPERKALEMIA
METABOLIC ACIDOSIS
LIFE THREATHENING EMERGENCIES IN CKD

Fluid overload/Pulmonary Edema

Hyperkalemia
Pericardial Effusion with tamponade
Metabolic acidosis
FEATURES OF HYPERKALEMIA

Muscle weakness
lower extremities and ascends, respiratory
muscles and those supplied by cranial nerves are
spared
abnormal cardiac conduction which can lead to fatal
arrhythmia
PERICARDIAL EFFUSION WITH TAMPONADE

Subacute tamponade
less dramatic; chest discomfort or easy
fatigue
hypotension with narrow pulse pressure
elevated jugular venous pressure

Acute tamponade
sudden onset
associated with chest pain and dyspnea
markedly elevated CVP
hypotension common
heart sounds muted
pulsus paradoxus
Manifestations of Metabolic acidosis

Involve the respiratory, cardiovascular, neurologic and

skeletal systems
Kussmaul’s respiration
increased susceptibility to cardiac arrhythmia
(hyperkalemia)
decreased level of consciousness due to a 2’ decrease
in intracerebral pH
Phosphorus
– A major component of bone, along with
calcium
– One of the first substances to be deranged in
CKD
Triggers a sequence of events that may ultimately
lead to renal bone disease
 Phosphate Binders
Further limits the
absorption of phosphate
by binding it in the gut
Administered with meals
Conventional binders
– Aluminum hydroxide
– Calcium salts
Recent developments
– Sevelamer hydrochloride
– Lanthanum carbonate
CARDIOVASCULAR DISEASE

Leading cause of morbidity and mortality in pts with CRD

at all stages
30-45% of pts reaching ESRD already have advanced
cardiovascular complications
Hypertension is the most common complication of CRD
and ESRD
Volume overload is the major cause of HPN in uremia
Anemia-normochromic, normocytic

Declining renal function –beginning at

stage 3
– reduced erythropoietin production
– decreased red blood cell half-life
– tendency toward gastrointestinal bleeding.
ABNORMAL HEMOSTASIS

Associated with prolongation of bleeding time

Decreased activity of platelet factor III
Abnormal platelet aggregation and adhesiveness
Impaired prothrombin consumption
Manifestations: increased tendency to abnormal bleeding and
bruising, occult GI bleeding
Greater susceptibility to thromboembolic complications esp
nephrotic pts
NEUROMUSCULAR ABNORMALITIES

Central, peripheral and autonomic neuropathy

Abnormalities in muscle composition and function
Due to retained nitrogenous metabolites and middle molecules and
PTH
Become clinically evident at stage 3
Mild manifestations- disturbances in memory,sleep and
concentration
Hiccups,cramps, fasciculations, twitching, asterixis, chorea seen in
uremia
Seizure and coma
GASTROINTESTINAL AND NUTRITIONAL
ABNORMALITIES

Uremic fetor-breakdown of urea in saliva

Gastritis, peptic disease, mucosal ulceration
Increased incidence of diverticulitis, pancreatitis
Anorexia, hiccups, nausea, vomiting
Protein-calorie malnutrition as a consequence of low protein and
caloric intake
ENDOCRINE AND METABOLIC DISTURBANCES

Impaired glucose metabolism- slowing of the rate of blood glucose

level after a glucose load
FBS usually normal or slightly elevated
Plasma level of insulin slightly elevated
Impaired response to insulin and glucose utilization
Drug dosing needed, some drugs cant be used, metformin
contraindicated when GFR is about 25-50%
Low estrogen level
Impotence, oligospermia, germinal cell dysplasia common
DERMATOLOGIC ABNORMALITIES

Pallor, defective hemostasis (ecchymoses, hematomas)

Pruritus, excoriations
Deposition of pigmented metabolites or urochromes (uremic frost)
Thank you and good day
 GFR differentiation
Stage 0 >90 (+) risk factors for CKD
Stage 1 ≥90 (+) evidence of kidney
damage (proteinuria, abnormal urine
sediment and imaging studies)
Stage 2 60 to 89
Stage 3 30 to 59
Stage 4 15 to 29
Stage 5 < 15