Chronic Kidney

Disease

Compiled by Tebatso Shai

 • Definition and classicification of CKD
• Pathophysiology
• Prevalence

Objective
• Clinical presentation
• Treatment goals

s • Complications of CKD
• Pharmacological and non-pharmacological
interventions
 • Defined as abnormalities in kidney structure or
function, present for 3 months or longer.
• It is a progressive loss of kidney function and
replacement of normal kidney structures with

WHAT IS parenchymal fibrosis which can occur of several

months to years

CKD
• CKD is classified according to level of kidney
function based on glomerular filtration rate (GFR)
from level 1-5 with increasing severity of disease.
• CKD stage 5 is also known as ESRD where GFR falls
below 15 mL/min per 1.73 m2 body surface area
 • Stage 1: Glomerular filtration rate ≥ 90 mL/min
CKD can be diagnosed with normal GFR if
other markers are present
Stages of • Stage 2: Glomerular filtration rate 60 – 89 mL/min

CKD • Stage 3: Glomerular filtration rate 30 – 59 mL/min

• Stage 4: Glomerular filtration rate 15 – 29 mL/min
• Stage 5 (end stage kidney disease): Glomerular
filtration rate < 15 mL/min
•KDIGO GFR and albuminuria categories
and prognosis of CKD by category.14 To
meet criteria for CKD there must be a
significant reduction in GFR (categories
3a-5) or there must also be evidence of
kidney damage (categories 1 and 2) for 3
months or greater. Prognosis Scale –
Green: low risk (if no other markers of
kidney disease, no CKD); Yellow:
moderately increased risk; Orange: high
risk; Red: very high risk. (CKD, chronic
kidney disease; GFR, glomerular
filtration rate; KDIGO, Kidney Disease:
Improving Global Outcomes.)
 • Susceptibility factors: Increase risk of kidney
disease but do not actually cause kidney damage
• Advanced age, race, low education/income,
low birth weight, family history, systemic
inflammation, dyslipidaemia
• Initiation factors: initiate kidney damage, these can
Pathophysiolo be modified by drug therapy
• Diabetes mellitus, hypertension, polycystic
gy kidney disease, HIV nephropathy
• Progression factors: cause further decline in kidney
function after initial kidney damage/persistence of
underlying initiation factors
• Glycaemia in diabetes, hypertension, smoking,
proteinuria, obesity.
 • Progression form CKD to ESRD can occur over years
to decades. Patients with stage 1-2 CKD are
typically asymptomatic (CKD can be entirely
asymptomatic until over 75% of kidney function is
lost)
• Nephron damage is typically through diabetes
Pathophysiolo mellitus, hypertension and pharmacological
therapy
gy • Nephron mass is lost as nephrons are damaged
• Total GFR likely to remain consistent due to the
hyperfunctioning of the remaining nephrons (intact
nephron hypothesis)
• Cycle continues-renal function declines-renal
structures damaged-GFR gradually drops
Sequence
of events • Infiltration of damaged kidneys with intrinsic

leading inflammatory cells

• Activation, prolofearation and loss of intrinsic renal

to cells
• Activation and proliferation of extracellular matrix

scarring
producing cells
• Deposition of extracellular matrix replacing the

and
normal architecture

fibrosis
 • There is a worldwide increase in CKD and kidney failure in the last
23 years
• CKD has moved from 36th cause of death in 1990 to the 19th cause of
death in 2013

Prevalenc • Lower socio-economic status is associated with higher morbidity

and mortality rates

e and
• In a meta-study done in 2018, the prevalence of CKD stages 1-5 was
15.8% and prevalence of CKD stages 3-5 was 4.6%
• With the increasing incidence of HPT, diabetes and HIV these

Prognosis figures are expected to rise

• According to a review of the USRDS 2009 report:
• Number of hospitalisations in ESRD patients is 1.9% per
patient/year
• Patients with CKD have 3-fold higher rates of hospitalisation and
hospital days spent per patient/year compared to the general
population
• CKD patients have higher risk of hospitalisation and CVD and this
risk increases with a decrease in eGFR
 • Patients with stage 1-2 of CKD usually do not present with
symptoms. They might only present with abnormalities of
urine volumes
• There are no pain receptors innthe kidneys therefore these
patients are less likely to complain with pain

Clinical • Patients with stages 3-5 are likely to present with metabolic
derangements such as anaemia, secondary
hyperparathyroidism, cardiovascular disease, malnutrition
Presentati and fluid and electrolyte abnormalities.
• Patients with stage 5 CKD are more likely to present with
on uremic symptoms symptoms (fatigue, weakness, shortness
of breath, mental confusion, nausea, vomiting, bleeding,
and anorexia), which are absent in stages 1-2 and minimal
in stages 3-4 but common in stage 5 CKD
• Other symptoms stage 5 CKD patients can also experince
itching, cold intolerance, weight gain, and peripheral
neuropathies.
Treatmen • CKD causes irreversible damage to the kidney
structures therefore the goal of therapy is to delay
the progression of the desease
t Goals • minimizing the development or severity of
complications
for CKD • Prevent NOT cure
 • Dietary protein restriction
• A low-protein diet (0.6 to 0.75 g/kg/day) can
delay progression of CKD in patients with or
without diabetes, although the benefit is
relatively small. Therefore, it’s a risk vs benefit
( Must not push patient into malnutrition)
Non- • Smoking cessation
pharmacologi • Smoking associated with increasing blood
cal pressure-associated with worsening CKD
therefore smoking cessation can prevent
Interventions further damage to the renal system
• Obesity and dyslipidaemias
• Obesity and dyslipidaemias risk factors for
diabetes and hypertension-worsening CKD
therefore healthy BMI can have protective
effects for the renal system
 • Objective of therapy is to protect kidneys
• Removing worsening factors ( nephrotoxic
Pharmacologi agents e.g NSAIDS)
• Management of co-morbidities ( dyslipidemias,
cal diabetes mellitus, hypertension)
Interventions • Treatment strategies dependant on presence or
absence of diabetes
 • Delaying progression of CKD involves treatment of
Complicati co-morbid conditions and compliccations that
arises from CKD
ons &co- • Hypertension
• Diabetes mellitus
morbidities • Hyperlipidemia

of CKD • Anaemia
• CKD-Mineral and Bone Disorder (CKD-MBD)
 • Ideal targets are: PCR <0.03 g/mmol or ACR <3 mg/mmol. Most
benefit is achieved by reducing protein creatinine ratio to <0.1
g/mmol or ACR <100 mg/mmol.
• Start treatment with a low dose of ACE-inhibitor and titrate up to
the maximum tolerated dose, e.g. Enalapril, oral, Start with 5 mg

Proteinuri
12 hourly and titrate to 20 mg 12 hourly, if tolerated.
• Monitor creatinine and potassium after 2 weeks if eGFR <60
mL/minute and after 4 weeks if eGFR >60 mL/minute.

a • Most benefit is achieved by reducing protein creatinine ratio

to <0.1 g/mmol or ACR <100 mg/mmol.
• If creatinine increases by >20% from the baseline, stop ACE-

reduction inhibitor and consult a specialist

• ACE-inhibitor not tolerated due to intractable cough: Consider an
angiotensin II receptor blocker (ARB), e.g.: Losartan, oral, Start
with 50 mg daily and titrate to 100 mg daily, if tolerated.
• ACEIs and ARBs are potassium sparing therefore potassium levels
needs to be monitored as these agents can cause or worsen
hyperkalaemia
 • Optimise BP control with additional antihypertensive agents. BP
control results in a lowering of proteinuria and slower decline in
eGFR.
• Combination therapy algorithm:
• Start ACEI/ARB
• Add diuretic
• CrCl ≥ 30 mL/min  thiazide diuretic
Hypertensi • CrCl < 30 ml/min  loop diuretic
• Add long-acting CCB
on co- • Substitute with β-blocker if angina, CHF,
arrhythmia

morbid • Add α/β blocker if not already used/add other

subgroup of CCB  dihydropiridine/non
• Add long acting α-blocker/central α-agonist (not with
B)/vasodilator
• Target BP for patients with hypertension: <140/90 mmHg.
• Target BP for patients with hypertension and confirmed CKD
and/or diabetes: <130/80 mmHg.
 • If hyperlipidaemia is a co-existent cardiovascular
risk factor, manage with statins
• Primary prevention (no existing CVD):
• Simvastatin 10mg at night OR atorvastatin
Hyperlipide 10mg at night (for patients on protease
inhibitors)
mia co- • Secondary prevention (existing CVD):
• Simvastatin 40mg at night OR atorvastatin
morbid 10mg at night (for patients on protease
inhibitors
• For patients on amlodipine, dose of simvastatin
should not exceed 20mg (drug-drug interaction)
 • In diabetics with kidney disease there is an
increased risk of hypoglycaemia. Insulin is the safer
option to control blood glucose in patients with
eGFR<60 mL/minute.
Diabetes • Insulin requirements will decrease as renal disease
progresses.
co- • Stop glibenclamide when eGFR <60 mL/minute
because of an increased risk of hypoglycaemia.
morbid • Reduce metformin dose when eGFR <60
mL/minute (maximum dose 500 mg 12 hourly).
• Discontinue metformin when eGFR <30 mL/minute
because of the risk of lactic acidosis.
 • 1. Anaemia of CKD
• Decrease production of erythropoietin by
interstitial fibroblasts
• Iron deficiency
• Decreased RBC lifespan
Consequen • 2. CKD-related bone and mineral disorder (CKD-
CMD)
ces of CKD • Imbalances of PTH, calcium, phosphorus
• Decreased interstitial calcium, raised PTH,
decreased bone growth
• Bone abnormalities
• Osteitis fibrrosa cystica; osteomalacia;
adynamic bone disease
 Calcium and phosphorus homeostasis is mediated through the effects of PTH,
1,25-dihydroxyvitamin D3 (calcitriol), and FGF-23 on bone, the GI tract,
kidney, and the parathyroid gland. As kidney function declines, there is a
decrease in phosphate elimination, which results in hyperphosphatemia and a
decrease in serum calcium concentration. Hypocalcemia is the primary
stimulus for secretion of PTH by the parathyroid glands. Hyperphosphatemia
also increases PTH synthesis and release through its direct effects on the
parathyroid gland. In an attempt to normalize ionized calcium, PTH increases
calcium reabsorption by the distal tubules and decreases phosphate
Pathophysiology reabsorption in the proximal tubules of the kidney (at least until the GFR falls
to approximately 30 mL/min/1.73 m2 [0.29 mL/s/m2]) and also increases

of CKD-MBD
calcium mobilization from bone. FGF-23 production in bone also increases in
response to high phosphate levels and increased PTH and promotes
phosphate excretion by the kidney. The result is a relative normalization of
calcium and phosphorus, at least in the early stages of CKD; however, this
occurs at the expense of an elevated PTH and FGF-23 (“the trade-off
hypothesis”). The increase in PTH is most notable when GFR is less than 60
mL/min/1.73 m2 (0.58 mL/s/m2) (CKD 3a and higher) and worsens as kidney
function further declines.32 With advanced kidney disease, the kidney fails to
respond to PTH or to FGF-23 and abnormalities in calcium and phosphorus
worsen. Over time, the negative effects of sustained hyperparathyroidism on
bone are realized as calcium resorption from bone persists.
Pathophysiology of CKD-MBD. (Ca, calcium; FGF-23, fibroblast growth factor-23; PTH, parathyroid hormone.) FGF-23 also increases in response to 1,25-
dihydroxyvitamin D3. These adaptations are lost as kidney disease progresses.
 • Anaemia may increase rate of CKD progression in a phenomenon known as
cardio-renal anaemia syndrome
• Patients on chronic haemodialysis or peritoneal dialysis are often anaemic
due to iron deficiency and deficiency of erythropoietin (EPO).
• Decreased production of erythropoietin by proximal tubular cells
• Normally levels respond to deoxygenation
• Higher Hb associated with poorer outcomes
• Manage with erythropoietin stimulating agent  ESA
• Iron demands increase with ESA  Therefore iron supplementation

Anaemia simultaneously
• Ferous sulphate 170mg 12 hourly OR ferrous fumarate 200mg
12 hourly
• Erythropoietin, 40–50 IU/kg/dose, IV/SC 2–3 times weekly and
assessed at 4 weekly intervals. If necessary, dose may be
increased by 25 IU/kg.
• Other mineral or vitamin deficiencies must be addressed  B12, folate
• Target Hb  11 – 12 g/dL (There is an increased risk of cardiovascular
events with haemoglobin levels >12 g/dL)
 • Calcium carbonate, oral, equivalent to elemental
calcium, approximately 500 mg 8 hourly with
meals.
• Increase to approximately 1 g 8 hourly with
meals, if hyperphosphatemia persists.
• If hyperphosphatasemia is still uncontrolled on
Hyperphosphatae calcium carbonate:
• Aluminum hydroxide BP (300 mg/5 mL), oral,
mia and/or 10 mL 8 hourly. Specialist initiated. (Not used
hypocalcaemia for longer than 3 months to prevent dementia-
associated aluminum toxicity)
• Hyperparathyroidism, if PTH is >2 times times
upper limit of normal range
• Calciferol, oral, 50 000 IU once weekly. OR
Calcitriol, oral, 0.25–4 mcg daily.
 • When fluid overloaded and eGFR <60 mL/minute,

Odema start:
• Furosemide, oral, 40 mg 12 hourly. Titrate to a
maximum of 500 mg 12 hourly.
Indication • Pericarditis or pleuritis
s for • Progressive uremic encephalopathy/neuropathy
with signs of confusion/seizures (urgent indication)
Renal • Fluid overload refractory to diuretics
• Poorly controlled HPT poorly responsive to
Replacem antihypertensives
• Metabolic disorders refractory to treatment
ent (hyperkalaemia, hyponatremia, metabolic acidosis,
hypercalcemia, hyperphosphatemia)
Therapy
Referenc • dipir
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