The document provides a comprehensive overview of chronic kidney disease (CKD), including its definition, staging, causes, clinical manifestations, diagnosis, and treatment approaches. CKD is characterized by a progressive loss of kidney function, often presenting with symptoms such as fluid retention, uremia, and anemia. Effective management focuses on reversing the underlying causes, relieving symptoms, and may involve dialysis or transplantation in advanced cases.

1. Chronic kidney disease
Dr. Kollum

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Objectives
• Define Chronic Kidney Disease (CKD)
• Staging of CKD
• Estimation of GFR: Formulae used
• Causes of CKD
• Clinical manifestation
• Significance of CKD
• Principles of treatment
• Prognosis
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Definition
• Progressive loss in kidney function over a period of months or
years (usu. more than 3 months)
• Presents with reduction in the glomerular filtration rate or the
presence of proteinuria
• Affects more than 10% in most populations
• More common in females
• Incidence increases exponentially with age, almost inevitable in
these over 80 years
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Staging of CKD
GFR Category GFR (ml/min/1.73 m2
) Terms
G1 ≥90 Normal or high
G2 60–89 Mildly decreased*
G3a 45–59 Mildly to moderately decreased
G3b 30–44 Moderately to severely decreased
G4 15–29 Severely decreased
G5 <15 Kidney failure
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Estimation of GFR from serum creatinine
• GFR is the volume of filtrate produced by the glomeruli of both
kidneys each minute
• Impossible to measure directly, so estimates made by looking at the
rate a substance, such as creatinine is removed by the kidneys
• Creatinine clearance is similar to GFR since nearly all filtered
creatinine appears in urine
• Measurement of GFR and creatinine clearance is tedius and
inaccurate as requires 24 hour urine collection
• Serum creatinine has thus been used to estimate renal function
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Formulae used to calculate creatinine clearance
1. Cockcroft-Gault equation
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Formulae…..
2. MDRD Formula
• A newer formula derived from the Modification of Diet in Renal Disease study
(Levey et al. 1999). It uses only the sex and age of patient and can be adjusted for
ethnicity
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3. Formula for Paediatric patients
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Estimation of renal function using urea
• Serum Urea is also commonly used to assess renal function
• Demerits: variable production rate and diurnal fluctuations in
response to protein content of diet, elevated by dehydration or an
increase in protein catabolism such as in GI hemorrhage, sepsis,
trauma, high dose steroid
• Rapid elevation of urea before any rise in corresponding creatinine
indicates progress into a prerenal state
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Causes of CKD
• Reduction in renal function results from damage to the infrastructure
of the kidney
• Nephrons are lost as complete units as well as the function, those left
have to cope with increased demand
• Patient remains well until so many nephrons are lost and the GFR
cannot be maintained despite activation of compensatory mechanisms
• Hence GFR progressively declines
• Identifying cause is useful to identify and eliminate reversible factors
and planning for likely outcomes and treatments
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Clinical manifestations of CKD
• Urinary symptoms
• Fluid retention
• Uremia
• Anemia
• Electrolyte disturbances
• Renal osteodystrophy
• Others
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1. Urinary symptoms
Polyuria due to medullary damage and osmotic effect of high plasma
urea levels (>40mmol/L)
Nocturia occurs as ability to concentrate urine is lost plus failure of
physiological nocturnal antidiuresis
Proteinuria: results from glomerular leaks, infection, failure of protein
reabsorption in the tubules or overflow of excess plasma proteins(as in
myeloma). Proteinuria greater than 2g in a 24 hour collection indicates
glomerular aetiology
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2. Fluid retention
Failure to excrete salt and water as GFR falls.
• Retention of extracellular fluid manifests as both peripheral and pulmonary
edema and ascites.
• In severe CKD sodium retention leads to circulatory volume expansion
leading to hypertension. Volume dependent hypertension occurs in 80% of
patients
• Raised BP exacerbates renal damage. Hypertension causes damage to
intrarenal vasculature, thickening walls of arterioles and small vessels. This
reduces renal perfusion leading to stimulation of the renin angiotensin
aldosterone system, leads to vasoconstriction result which exacerbate
degree of hypertension
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3. Uremia
• Blood level of urea is used to estimate the degree of toxin
accumulation in uremia.
• Symptoms are many and vary: anorexia, nausea, vomiting,
constipation, foul taste, skin discoloration and severe pruritus.
• Severe cases crystalline urea is deposited on the skin (uremia frost),
increased tendency to bleed
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4. Anaemia
• Normochromic, normocytic anemia, Hb levels fall to 6-8g/dl in end-
stage renal failure.
• Principal cause is damage of peritubular cells hence inadequate
secretion of erythropoietin which is main regulator of red cell
proliferation and differentiation in the bone marrow
• Major cause of fatigue, breathlessness at rest and on exertion,
lethargy and angina
• Compensatory hemodynamic changes occur such as increased cardiac
output though leads to tachycardia and palpitations
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5. Electrolyte Disturbances
• Hypernatraemia and hyponatraemia depends on condition and
therapy employed
• Hyperkalemia: levels of over 7.0 mmol/L are life threatening and can
lead to cardiac arrest.
• Hydrogen ions: common end product of many metabolic processes.
About 40-80 mmol are excreted daily. In renal failure it is retained
causing acidosis
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6. Renal osteodystrophy
Four types of bone disease associated with CKD:
i. Secondary hyperparathyroidism
ii. Osteomalacia: reduced mineralization
iii. Mixed renal osteodystrophy: both hyperparathyroidism and
osteomalacia
iv. Adynamic bone disease: reduced bone formation and resorption
Impaired hydroxylation of cholecalciferal in kidney – vitamin D
deficiency – defective mineralization of bone and osteomalacia
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7. Others
• Hypocalcaemia: vitamin D deficiency, reduced absorption from the
gut
• Hyperphosphataemia: due to reduced phosphate excretion,
sequesters calcium in bone and soft tissue as calcium phosphate
• Low calcium and low vitamin D results in increased secretion of
parathyroid hormone (PTH) leading to osteosclerosis(hardening of
bone)
• Neurological changes: non specific. Inability to concentrate, memory
impairment, irritability, stupor
• Muscle cramps and restless leg especially at night
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Diagnosis of CKD
• May be suspected because of signs and symptoms
• Most often discovered during routine investigations for other diseases
• Family, drug and social histories are key in elucidating causes of renal
failure
• Physical exam may be helpful: signs of anemia and skin pigmentation,
ankle edema and raised jugular venous pressure suggests fluid
retention, in severe disease fishy smell in breath (uraemic factor),
palpable kidney and bladder
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Diagnosis…..
• Kidney function assessment: serum creatinine, serum urea,
hyperkalemia, acidosis with low serum bicarbonate, hypocalcaemia,
hyperphosphataemia
• Urine examination visually and microscopically
• Structural assessment of the kidneys: ultrasound, intravenous
urography, abdominal radiography, CT scan, MRI and MRA
• Renal biopsy
• Graphic plots of GFR
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Treatment
Main aims are:
1. Reverse or arrest the process causing renal
damage
2. Relieve symptoms and avoid worsening conditions
3. Implement regular dialysis and/ or transplantation
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1. Reversal or arrest of primary disease
• Surgical removal of post renal obstruction
• Treat glomerulonephritis with immunosuppresants or steroids
• Stop offending agent in drug induced renal disease
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2. Relieve symptoms and avoid worsening conditions
Hypertension
• Adequate control of BP is most crucial to avoid vicious circle of events
• Antihypertensive therapy may lead to improvement in renal function
• Drugs used same as those in other forms of hypertension
• Diuretics are used in fluid overload, loop diuretics
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Management of uremia
• Dietary modifications: reduced dietary protein intake, sodium
restriction, potassium restriction and vitamin supplementation
• Fluid retention: Dialysis and diuretics used, restrict fluid intake
• GIT symptoms: nausea and vomiting may require antiemetics
Constipation: Laxatives
• Pruritus: Antihistamines
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Anemia
• Use of recombinant human erythropoietin (epoietin alpha and β
• Correct any iron and folate deficiency before therapy
• Concurrent iron supplements required
• Initial epoietin dose of 50units/kg iv or sc is given three times a week
then increased in steps of 25 units/kg every 4 weeks to produce a Hb
of not more than 2g/dl per month
• Correcting anemia helps control symptoms of lethargy and myopathy
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Acidosis
• CKD may result in metabolic acidosis. May be treated with sodium
bicarbonate 1-6g/day
• If severe, dialysis may be required
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Osteodystrophy
Due to 3 factors:
I. Hyperphosphatemia: Restrict diet, use phosphate binders
II. Vitamin D deficiency: Synthetic vitamin D analogues may be used,
doses adjusted with serum calcium level in consideration
III. Hyperparathyroidism: manage calcium levels, surgery may apply
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Dialysis and renal transplant
• End stage renal failure patients require dialysis or transplantation to
survive
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Significance of CKD
• CKD indicates progression to end-stage renal failure (ESRF)
• Strong association with accelerated cardiovascular disease, increases with
severity
• Inadequate control of blood pressure may enhance progression to more severe
stages and ESRF
• Most patients with mild CKD (stages 1 to 3) may remain stable for years or
decades and are frequently asymptomatic
• Recognition of these mild stages allows for early treatment of cardiovascular
risk factors and identify those with progressive disease
• Severe CKD(stages 4 and 5) frequently have symptoms of uremia, though
onset is slow and insidious
• Common for patients to present when already in ESRF
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Resources
• Roger Walker, Cate Whittlesea. Clinical Pharmacy and Therapeutics.
4th Edition
• https://www.utoledo.edu/med/depts/medicine/.../Vetteth_Chronic_
Kidney_Disease.ppt
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