February 17,

CHRONIC KIDNEY DISEASE

2017

Definition:
Irreversible impairment of renal function for at least 3 months based on the abnormal
structure or function or GFR 60 mL/min/1.73 m2 for at least 3 months with/ without
evidence of kidney damage.
Stages of CKD:
Two GFR values, 3 months apart are required to assign a stage.
Stage GFR mL/min/1.73 Description Prevalence Clinical presentation
m2
1 90 Norma or elevated 6.5% Asymptomatic
GFR with other
evidence of renal
damage
2 60-89 Slight drop in GFR Asymptomatic
with evidence of renal
damage
3A 45-59 Moderate drop in GFR 4.5% Usually asymptomatic
with or without
3B 30-44 Anemia in some patients
evidence of other
Most are nonprogressive or
renal damage
progress very slowly.
4 15-29 Severe drop in GFR 0.4% First symptoms often at GFR 20
with or without Electrolyte problems likely as GFR
evidence of other falls
kidney damage
5 15 or on dialysis Established renal Significant symptoms and
failure complications usually present
Dialysis initiation at GFR 10
*kidney damage; pathologic abnormalities or markers of damage including abnormal urine
tests or imaging studies ( proteinuria, hematuria, abnormal anatomy, systemic disease).

Causes:
1. Diabetes is the most common cause (30% of cases); more common in type II than I
2. Hypertension is responsible for 25%
3. Glomerular diseases are responsible for 15% of cases; IgA nephropathy being the most
common.
4. Interstitial nephritis (20-30%); often drug induced
5. Systemic inflammatory disease (5-10%); SLE, vasculitis
6. Renovascular diseases 5%; mostly atheromatous
7. Congenital and inherited kidney diseases (5%); adult polycystic kidney disease is the
most common inherited cause of CKD. Rare inherited disorders include Alports
syndrome.
8. Peylonephritis and reflux nephropathy
9. Any cause of AKI if prolonged or treatment is delayed can lead to CKD
10. Obstructive uropathy (rare cause)
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2017

11. Unknown: up to 20%

Epidemiology: it is more common in African American than in Caucasian patients.
Screening is recommended for high risk patients:
1. Diabetes mellitus
2. Hypertension
3. Cardiovascular diseases (IHD, cerebrovascular disease, peripheral vascular disease)
4. Structural renal diseases e.g. known stones, BPH
5. Recurrent UTI, or childhood history of vesicouretric reflux
6. Multisystemic disorders that involve the kidneys e.g. SLE
7. Family history of ESRD or known hereditary disease e.g. APKD
8. Opportunistic detection of hematuria or proteinuria

Clinical features:
General symptoms:
Most patients with slowly progressive disease are asymptomatic until GFR is less
than 30 mL /min/1.73 m2 (stage 4 or 5 CKD* see later*).
An early symptom is nocturia due to loss of concentrating ability and incensed
osmotic load per nephron but this is not specific.
Once GRF falls below 30 ml/min/1.73 m2, patients will have tiredness and
restlessness (due to renal anemia), anorexia, pruritus, weight loss, nausea and
vomiting. With further deterioration, patients may have deep respiration
(Kussmaul respiration due to metabolic acidosis), and develop muscular
twitching, fits, drowsiness and coma.
Immune dysfunction; uremia inhibits cellular and humeral immunity with
increased susceptibility to infections; the second most common cause of death
in dialysis after cardiovascular diseases.
Hematologic:
1. Normocytic normochromic anemia
Life threatening compli ca tions in
CKD: Mechanisms:
Eryhthropoietin deficiency
1.Hyperkalemia : obtain ECG, be
Toxic effects of uremia on marrow precursor cells
awa re tha t K level can be hi gh
wi thout ECG changes.
Reduced RBC survival
Increased blood loss due to capillary fragility and poor platelet
2.Pul mona ry edema seconda ry to function.
volume overload- look for recent
Reduced intake, absorption and utilization of dietary iron.
weight gain.
2. Bleeding tendency due to uremia induced platelet dysfunction. Platelets
3.Infections (UTI, sepsis, pneumonia) dont granulate in uremic environment.
Fluid and Electrolyte abnormalities:
1. Hyperkalemia, hyperphsphatemia, hypermagnesemia; due to reduced renal
excretion.

-Azotemia refers to
elevation of BUN.
-Uremia refers to the signs
and symptoms associated
with accumulation of
nitrogenous wastes due to
impaired renal function.
Rarely occurs unless the
BUN is 60 mg/dL
February 17,
CHRONIC KIDNEY DISEASE
2017
2. Metabolic acidosis: due to the following:
Kidneys are unable to excrete H+
Loss of renal mass and thus reduced ammonia production ( and
therefore inability to excrete H+)
3. Fluid overload and pulmonary edema.
Neurologic and muscle problems:
1. Symptoms include:
o lethargy,
o somnolence,
o confusion,
o sensory and motor peripheral neuropathy (paresthesia and foot
drop) and
o Uremic seizures.
o Restless leg syndrome: neuropathic pain in the legs that is only
relieved with movement. Patients legs are jumpy during the night.
2. Physical findings:
o Weakness
o Asterixis
o Hyperreflexia
3. Generalized myopathy occurs due to poor nutrition, hyperparathyroidism,
vitamin D deficiency and disorders of electrolyte metabolism. Muscle
cramps are common.
4. Hypocalcemia can cause lethargy, confusion and tetany.
GI problems due to uremia include N&V and loss of appetite (anorexia).
Cardiovascular diseases:
Risk is incaresed in patients with stage 3 and worse CKD (GFR less than
60ml/min/m2) and those with proteinuria or microalbuminuria.
1. HTN secondary to salt and water retention. Decreased GFR stimulates RAAS.
Renal failure is the most common cause of secondary HTN. Left ventricular
hypertrophy can develop secondary to HTN with increased risk of sudden
death from dysrhythmias.
2. Pericarditis due to uremia.
3. CHF- due to volume overload, HTN and anemia.
4. Medial vascular calcification in stage 3b and above due to
hyperphosphatemia.
Endocrine/ metabolic problems:
1. Disturbance of calcium and phosphorous metabolism:
Renal tubular cell damage and hyperphsphatemia results in reduced
conversion of 25-hydroxyvitamin D to its active metabolite, 1,25-
hydroxyvitamin . this results in hypocalcemia and secondary hyper-
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CHRONIC KIDNEY DISEASE
2017

parathyroidism which removes calcium from bones making them

Renal os teodys trophy refers to bone
diseases tha t develop in CKD;
ma nifes ting as bone pain, proximal
mus cle weakness , fra ctures , pruri tus ,
and extraskeletal cal cifi ca tions .
1.Os teomalacia : due to reduced bone
mi neraliza tion from reduced Ca
reabsorption ( due to reduced a cti ve
Vi t D).
2. os teoporosis due to malnutri tion.
3. os tetis fibrosa cys ti c due to
increased bone turnove r secondary
to hyperpa rathyroidism. ( boney
lesions a re more prominent in dis tal
phalanges and la teral cla vi cles)
weak and susceptible to fracture.
Secondary hyperparathyroidism results in renal osetodystrophy
(weakness of bones and possible fractures).
Hyperphosphatemia can cause calcium and phosphate to
precipitate causing vascular calcifications that may result in necrotic
skin lesions called calciphylaxis.
Note that long-standing hyperparathyroidism and calcium based
phosphate binders may sometimes cause hypercalcemia.
2. Sexual/reproducrtive symptoms due to hypothalamic-pituitary
disturbances and gonadal response to sex hormones:
Reduced libido in both genders due to hypogonadism as a
sequence of hyperprolactinemia.
Reduced testosterone in men
Amenorrhea, infertility in women
3. Pruritus due to hyperphosphatemia. It is a common problem and
difficult to treat. Dialysis and ultraviolet light used.
4. The half life on insulin is prolonged due to reduced tubular metabolism
of insulin. Insulin requirements therefore are unpredictable in diabetic
patients in advanced CKD.

Monitoring renal function:

Estimated GFR using 24 h Cr clearance or radioisotope scan.
Loss of renal function in CKD is constant. Rapid decline in renal function in renal function may be
due to infections, dehydration, uncontrolled HTN, metabolic disturbance, obstruction,
nephrotoxins.
Importance of falling GFR:
- A falling GFR is an independent risk factor for cardiovascular diseases (chief cause of death
from renal failure).
- Good renal function is essential for optimum internal environment.
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CHRONIC KIDNEY DISEASE
2017

Investigations:
Blood
CBC (+ Fe, ferritin, Normocytic normochromic anemia (exclude common non-renal explanations then
folate, vitamin manage as renal anemia)
B12) Thrombocytopenia
Calcium, Hypocalcemia, hyperphosphatemia and high PTH, high alkaline phosphatase
phosphate and To assess renal osteodystrophy
PTH, alkaline
phsophatase
Albumin Consider malnutrition, anemia
Urea and To assess stability/progression; compare to previous results.
creatinine Serum Cr doesnt rise until theres is 50% loss of renal function
Serum To identify hyperkalemia and metabolic acidosis
electrolytes (K+,
ca, PO4-3 serum
protein)
Hepatitis and HIV serology if dialysis or transplant is planned. Hepatitis B vaccination is recommended if
seronegative.
Urinanalysis
Dipstick and 24 h Proteinuria and hematuria may indicate the cause. Proteinuria indicates risk of
urine protein progressive CKD requiring preventive ACEi or ARB.
Albumin: Cr ratio
Cr clearance to estimate GFR
Lipids, glucose, Cardiovascular risk high in CKD; treat risk factors aggressively
HbAIc
Renal ultrasound To evaluate the size of kidneys and rule out obstruction. Only if there are urinary
symptoms (to exclude obstruction) or progressive CKD.
- Small kidneys suggest chronic renal insufficiency with little chance of
recovery. ( 9 cm)
- Asymmetric renal size suggests renovascular or developmental disease.
Consider MAG3 renogarm to look at contribution of each kidney to overall
function.
- Kidneys are enlarged in APKD, DM and infiltrative disorders (amyloid and
myeloma).
Presence of normal sized or enlarged kidneys doesnt exclude CKD.
ECG If hyperkalemic, or older than 40yrs, or there are risk factors for cardiac disease.
Renal biopsy If rapidly progressive disease, or unclear course and normal sized kidneys.

Renal biopsy:
It should be done only when knowing the histology will influence the
management. In CKD, kidneys are small, there is a higher risk of bleeding from
biopsy and the results are usually unhelpful.
Indications:
1. Unexplained AKI or CKD
2. Acute nephritic syndrome
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CHRONIC KIDNEY DISEASE
2017

3. Unexplained proteinuria and hematuria

4. Systemic diseases associated with kidney dysfunction
5. Suspected transplant rejection
6. To guide treatment
Contraindications:
Mild-moderate CKD is managed in 1. Abnormal clotting
general practice or by other
physicians. Criteria for referral to
2. HTN ; BP 160/90 mmHg
nephrologist: 3. Single kidney except for renal transplants
4. CKD with small kidneys 9 cm
-Stage 4 and 5 CKD
5. Uncooperative patient
-significant hematuria after excluding 6. Horseshoe kidney
UTI and urological abnormalities such
as stones and tumors.
7. Renal neoplasm
Pre-procedure:
-Significant proteinuria; ACR
1. Check CBC, coagulation profile and group.
70mg/mmol or PCR 100 mg/mmol
2. Obtain informed consent
-Rapid deterioration in renal function 3. US to delineate the anatomy
( fall in eGFR 5 mL/min/1.73m2 in
one year or 10 mL/min/1.73m2
4. Stop anticoagulants (aspirin 1 week, warfarin 2-3 days, LMWH 24 hours)
over 5 years. Post-procedure:
1. Bed rest for at least 6 hours
-Age 40 years
2. Monitor BP, pulse, symptoms and urine color.
-Poorly controlled HTN despite use of 3. Complication: bleeding is the main common complication; mostky
medications
occurring within 8 hours but can be delayed by up to 72 hours.
-Known or suspected genetic causes Macroscopic hematuria occurs in 10% of patients although blod
of CKD.
trasnfuison is only needed in 1-2%.
-Suspected renal artery stenosis. 4. Aspirin or warfarin can be restarted the next day if the procedure is
uncomplicated.
Management: 4 main approaches as follows
1. Investigation and treatment of reversible causes: relieve obstruction, stop nephrotoxic
drugs, and deal with high Ca and cardiovascular risk. Symptomatic volume
overload and hyperkamia
in CKD patients are the
2. Limiting progression and complications: most common
Dietary and lifestyle modifications: refer the patient to a dietician complications that require
Protein restriction to 0.6- 0.8 g/kg per day. Early protein restriction urgent intervention.

slows the progression of ESRD.

Potassium restriction when GFR 10-20 mL/min/1.73m2. instake should be less
than 60 mEq/day. Advise the patient to avoid high potassium foods ( bananas,
tomatoes and caffeine)
Phosphorous restriction:when GFR less than 50 mL/min/1.73m2. Phosphorous
level should be kept below 4 mg/dL. The patient should avoid phosphorous rich
food ( eggs, dairy products and meat)
Magnesium restriction
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CHRONIC KIDNEY DISEASE
2017

Carbohydrate and fat are adequate to provide energy.

Salt restriction only if HTN, CHF, edema or oliguria are present.
Fluid restriction for edema.
Smoking cessation
BP control slows the progressions:
Target BP 130/80 mmHg ( 125/75 if diabetic or ACR 70)
Salt restriction
ACEi/ ARB are the preferred agents( should be prescribed in all patients with
diabetic nephropathyand those with proteinuria irrespective if HTN is present or
not). They dilate the efferent arterioles in the glomerulus. If used early they
reduce the risk of progression to ESRD because they slow the progression of
proteinuria. But they must be used with great caution as they can cause
hyperkalemia.
Multiple drugs may be required including diuretics, CCB, BB.
Nifedipine and nitroprusside in emergency.
Glycemic control in diabetics.
Cardiovascular modification with statins and low dose aspirin. In CKD stage I and II, the
risk from cardiovascular death is higher than the risk of reaching ESRD. Weight loss and
exercise.
Renal bone disease: management should be started early
Correction of serum calcium: patients with CKD should be on long term oral
calcium and vitamin D.( Vitamin D3 alfacalcidol)
Treat secondary hyperparathyroidism by correction of hyperphosphatemia
through dietary restriction, oral phosphate binders preferably calcium
carbonate (citrate) or aluminum hydroxide if the previous one is ineffective.
3. Symptoms control:
Anemia :
Replace Vit B12/iron/folate if needed.
Recombinant erythropoietin ( side effect is HTN)
Target Hb is 10-12 g/dl; correcting Hb to normal level risks IV access and
arteriovenous fistula thrombosis, MI, HTN.
Acidosis: oral sodium bicarbonate. This can also slow the progression of CKD. Causation
in patients with HTN as sodium load can cause elevation of BP.
Correction of electrolyte abnormalities:
Correction of hyperkalmeia: more than 4.6 mEq/L
Dietary restriction and avoid medications that cause hyperkalemia:
Predisposing factors: K- sparing diuretics, ACEi, NSAIDS, beta blockers, infection,
hemolysis and trauma.
For cardiac arrhythmia management see AKI
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CHRONIC KIDNEY DISEASE
2017

Edema: loop diuretics ( furosemide) in high doses 250 mg-2 g a day +/-
metolazone 5-10 mg orally each morning. Fluid and sodium restriction is
needed. If these measures fail, dialysis should be done.
For pulmonary edema see AKI
Pruritus (due to urinary pigment in skin (urocchrome)): try capsaicin
cream or cholestyramine and UV light.
Restless leg syndrome:
o Check ferritin as low levels worsen the symptoms.
o Clonazepam 0.5-2 mg daily or gabapentin may help.
o Quinine sulfate 300 mg can help with cramps.
4. Preparation for RRT; dialysis and renal transplantation

History taking in CKD:

Investigate for possible causes: ask about previous UTIs, LUT symptoms, PMH of
diabetes, HTN, IHD, systemic disorders, renal colic. Drug and family history. Systemic
review.
Current status: uremic symptoms such as anorexia, vomiting, restless leg syndrome ,
fatigue, weakness, bone pain, amenorrhea (women), impotence ( in men), oliguria,
dyspnea and ankle swelling.
Physical examination of a patient with CKD:
Look for:
Cause of ESRD/CKD
Current mode of RRT and any complications.
Previous type of RRT and any complications ( arteriovenous fistula, parathyroidectomy
scar.
1. General appearance:
Mental status: conscious, drowsy, comatos..
Hyperventilation indicates metabolic acidosis
Hiccups
Sallow complexion due to impaired excretion of urinary pigments ( urochromes)
combined with anemia.
Hydration status: dehydrated/ edematous
Twitching due to myclonic jerks and epileptic seizures.
2. Face :
Pallor of anemia
Yellow tinge of uremia
Uremic fetor: urine like odor on the breath of person with uremia.
Gum hypertrophy from cyclosporine
Cushingoid appearance from steroids.
Mucosal ulcers due to dryness from reduced saliva, thrush.
3. Neck:
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CHRONIC KIDNEY DISEASE
2017

Current or previous tunneled line insertion ( if removed look for a small scar over the
internal jugular vein, and a larger scar in breast pocket area from the exit site).
Scar from parathyroidectomy.
4. Hands:
Half and half nails ( Tarrys nail): show the proximal portion of the nail white and the
distal half red, pink, or brown, with a sharp line of demarcation between the two
halves.
Anemia: pallor palmar creases
Flapping tremors
5. Periphery:
HTN
Arteriovenous fistula ( thrill, bruit)
Signs of previous transplant: bruising from steroids/ skin malignancy from
immunosuppression.
Scratch marks from pruritus/ excoriation
Uremic frost: fine white powder present on skin due to precipitation of high
concentration of urea in sweat.
6. Chest: auscultate heart for pericardial rub and lungs for pulmonary edema and pneumonia.
7. Abdomen:
Look for peritoneal dialysis catherter or signs of previous catheter (small midline scar
just below the umbilicus and small round scar to side of midline from exit side). Look
for signs of previous transplant (hockey-stick scar, palpable mass).
Ausculate for renal bruit
Palpation: ballotable polycystic kidney
8. Back:
Examine for sacral edema
Renal punch: to elicit tenderness in renal angle as a manifestation of renal infection.
Strike vertebral column with base of fits gently to elicit tenderness due to
osteodystrophy.
9. Legs:
Examine for edema
Look for signs of (diabetic) peripheral neuropathy (absent reflexes, reduced sensation,
paresthesia, restless legs)
10. Fundi: look for retinal changes of diabetes and HTN.
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CHRONIC KIDNEY DISEASE
2017

Differentiation of AKI verus CKD:

Features Favors CKD Favors AKI
Anemia Usually present May be present
Serum BUN Stable BUN increases 20-40 mg/d
and Cr Cr increases 2-4 mg/d
Serum Normal until end stage High particularly in oliguric phase
potassium
Serum Significantly high when serum Cr is High
phosphorous 3 mg/dL
Serum Low Low
calcium
Urine output 1 L daily until end stage Oliguric (urine output 50 mL/day )
without uremic symptoms
Renal US Small kidneys
Reversibility Return of renal function to normal with
time.
pH Acidosis Acidosis
Urinlaysis with broad casts ( more
than 2-3 WBC diameter)
Hx of kidney disease, HTN,
abnormal urinalysis, edema.