RENAL FAILURE/KIDNEY INJURY

ACUTE KIDNEY DISEASE CHRONIC KIDNEY DISEASE

Definition ACUTE KIDNEY INJURY • CKD is defined as abnormalities of
• Sudden decrease in renal function that is kidney structure or function,
present for > 3 months, with
accompanied by retention of nitrogenous and a
implications for health.
disturbance of water and electrolyte balance.
• Chronic kidney disease is defined
• OLIGURIA: Reduction in urine output to less than as either kidney damage or GFR
300ml/m²/day or <1ml/kg/hr <60 ml/min/1.73m² for > 3 months
• ANURIA: No urine, defined as urine <75ml/day in with implication for health.
an adult or <1ml/kg/day in children • Kidney damage is defined as
• POLYURIA: Urine output >4ml/kg/hr pathologic abnormalities or
• AZOTAEMIA: high nitrogenous waste as indicated markers of damage, including
abnormalities in blood or urine
by high urea. A reflection of renal dysfunction but
tests or imaging studies, Hx of
maybe due to non-renal causes kidney transplantation
e.g. - High protein diet,
- Hormones (glucocorticoids), • Kidney damage for ≥3 months, as
defined by structural or functional
- High catabolic rate, surgery, trauma, infection etc.
abnormalities of the kidney, with
or without decreased GFR,
• URAEMIA: Uraemia is the symptom complex manifest by either:
reflecting organ dysfunction that occurs when -Pathological abnormalities; or
kidneys fail to regulate body composition. -Markers of kidney damage, including
Rationale for Current Definition abnormalities in the composition of the
● Before 2002 several definitions were utilised blood or urine, or abnormalities in imaging
● RIFLE criteria in 2002 tests
● In 2005 the AKIN criteria developed published in 2007 -GFR < 6 0 ml/min/1.73m² for > 3
● pRIFLE criteria for children- 2007 months, with or without kidney damage
Rationale for classification
Even small elevations in serum creatinine levels associated with:
 Stages of Chronic Kidney Disease: A
Clinical Action Plan
The RIFLE classification of ARF is as follows:
• Risk (R) -Increase in serum creatinine level x 1.5 or
decrease in GFR by 25%, or UO <0.5 mL/kg/h for 6
hours.
• Injury (I) -Increase in serum creatinine level x 2.0 or
decrease in GFR by 50%, or UO <0.5 mL/kg/h for 12
hours.
• Failure (F) -Increase in serum creatinine level x 3.0,
decrease in GFR by 75%, or serum creatinine level >4
mg/dL; UO <0.3 mL/kg/h for 24 hours, or anuria for
12 hours.
• Loss (L) -Persistent ARF, complete loss of kidney
function >4 wks.
• End-stage kidney disease (E) -Loss of kidney
function >3 months
pRIFLE
 AKIN classification

KDIGO AKI DEFINITION & CLASSIFICATION

Epidemiology Epidemiology-
IFE: Olowu
 Primary renal disorders (29%)
 • Renal burkitt lymphoma 47.2%
• GN: 37.8%
• NS: 16.7%
 Secondary renal disorders (71%)
• Malaria 42.53%
• Septicaemia 28.73%
• Gastroenteritis 10.34%

P.Harcourt
Anochie and Eke
G/enteritis 28.9%,
Septicaemia 15.2%,
AGN 13.7%
P. falciparum 13.7%
Birth asphyxia 12.8 %

Etiology/Pathophysiology Pathophysiology Aetiology

of AKI • Chronic glomerulonephritis
• Chronic pyelonephritis
• Renal dysplasia
• Cystic diseases
• Urologic abnormalities
- Obstructive uropathies
- Reflux nephropathy
- Urinary tract malformations
• Systemic - SLE, H.S.P.
• Vascular - HUS
• Tumours - Bilateral
Wilms
-----------------
• Chronic glomerulonephritis
25.8%
• Reflux nephropathy and
obstructive uropathy
Conceptual model of AKI 24.2%
(Check ) Hereditary/familial
15.6%
NOVEL BIOMARKERS Dysplasia
13.5%
Multisystem dx
10.2%
N:B -Majority of cases in Nigeria are due to
steroid resistant nephrotic syndrome.

*******PATHOGENESIS
• Once critical level of deterioration
reached

Evolution of acute kidney injury ↓

Injury begins before excretory function is lost (ie,
decreased GFR) and can in some cases be detected by Progression
the measurements of biomarkers. Such biomarkers can Hyperfiltration
also be used for diagnostic and prognostic assessment. Phosphate retention
GFR=glomerular filtration rate. NGAL=neutrophil Proteinuria
gelatinase-associated lipocalin. Cys C=cystain C. KIM-
1=kidney injury molecule 1. IL-18=interleukin 18.
GST=glutathione-S-transferase. L-FABP=liver fatty-acid-
binding protein. CRP=C reactive protein. IL-6=interleukin
6.
Research techniques based on proteomics
1) Concentrations of these biomarkers seem to change
earlier than do serum creatinine concentrations (figure
3).82
Typically, these biomarkers have been most extensively
assessed after cardiac surgery or on presentation to the
emergency department.83—85
2) they seem to show different aspects of renal injury.
cystatin C concentrations - changes in glomerular
filtration rate,
neutrophil gelatinase-associated lipocalin - tubular stress
or injury.
3) these biomarkers seem to change with treatment or
recovery, which suggests that they can be used to
monitor interventions.94
4) they can identify subpopulations of patients who do
not have acute kidney injury according to creatinine-
based criteria, but actually have a degree of kidney stress
or injury that is associated with worse outcomes.
5) They increase our understanding of the pathogenesis
of acute kidney injury.
neutrophil gelatinase-associated lipocalin- most studied
renal biomarker,95—99
Others under investigation.
Inroduce additional cost (£5—20 per test) ?worthwhile,
? Therapeutic benefits
Key potential pathways implicated in pathogenesis of
acute kidney injury due to ischaemia or sepsis
The timing of activation
of each pathway, their interaction, and the hierarchy of
these pathways remain unknown. RAAS=renin–
angiotensin–aldosterone system. TGF=tubuloglomerular
feedback.

Changes in renal haemodynamics

Nitric oxide
Prostaglandins
Adenosine
Endothelin
Renin Angiotensin system.
Nephronal factors.
Medullary thick ascending limb
Straight segment of the PT
Intratubular obstruction and back leak
Cellular and metabolic alterations
Reactive oxygen molecules and free radicals
Adenine nucleotide metabolism
Loss of cellular polarity
Growth factors

AETIOLOGY
 Pre renal
-Hypovolaemia
-Peripheral vasodilatation
e.g. sepsis
-Reduced cardiac output
e.g. CCF

 Renal
-AGN
 -HUS
-Septicaemia
-Acute malaria
-Pyelonephritis
-Drugs: aminoglycosides,
-Renal vascular occlusion
-Vasomotor: ACEI,
Cyclosporin, NSAID
-Interstitial nephritis
Penicillin, NSAID, Diuretics
 Post renal
-Obstruction in a solitary kidney
-Bilateral ureteral obstruction
-Urethral obstruction- PUV

Notes:
 Pre renal
◦ Decreased true intravascular volume
◦ Decreased effective intravascular volume
Post renal
-PUV
-PUJ
-VUJ
-Neurogenic bladder
-Calculi
-Ureterocele
-Tumours
-Trauma
 Intrinsic renal
◦ ATN
◦ Hypoxic ischaemic insults
◦ Drug induced
◦ Toxins- endogenous or exogenous
◦ TLS with uric acid nephropathy
 ◦ Glomerulonephritis
◦ Interstitial nephritis- Drug induced or
idiopathic
◦ Vascular lesions- RAS, RVT, HUS
◦ Systemic disease with renal Cx e.g SLE

Developed countries
 1980s:
 HUS, septicaemia, burns and hypoxic
ischaemic insults
 1990s and since 2000 – additional causes
 Complications of
 advancement in cardiac surgery
 management of malignancies
 Stem cell and solid organ
transplantation

Uniqueness/Types/Classification
Presentation/Clinical Features • History pointing to aetiology • Antenatal detection of conditions
• OLIGURIA that can cause CRF
• Features of fluid retention • Failure to thrive
• Dyspnoea • Short stature
• Cough • History of recurrent UTI
• Headache • Enuresis
• Convulsion
• Pallor • RESP
• Hypertension - Acidotic breathing
• Acidotic breathing - Uraemic breath
• Features of heart failure - Pulmonary oedema
- Pleural effusion
Clinical Features - ARI
Pre –renal cause • CVS
History -Hypertension
• History of severe fluid losses or maldistribution -CCF
e.g Severe diarrhoea & vomiting -Uraemic - pericarditis
• Significant blood loss or massive burns -Arrhythmias
• Septic Shock • HAEMATOLOGY
• Profound heart failure -Pallor
• Oliguria -Bleeding
• Nephrotic syndrome (with excessive diuresis)
• GIT
Examination -Anorexia
• Tachycardia -Vomiting
• Weak pulses -GI bleeding
• Poor peripheral perfusion • CNS
• Hypotension - Seizure
• Features of dehydration. - Uraemic encephalopathy
• MSS
Intrinsic renal cause: - Renal osteodystrophy
History- Features of the FFING • SKIN
• Prolonged, uncorrected period of shock, oliguria - Pruritus
• Massive Intravascular haemolysis - Uraemic frost
• Recent sore throat or skin infection [Uremic frost is an uncommon
• Perinatal asphyxia dermatologic manifestation of profound
• Septicaemia or multiorgan infection azotemia and occurs when urea and other
• Bloody diarrhoea nitrogenous waste products accumulate in
• Medication Hx e.g gentamicin, NSAIDS, sweat and crystallize after evaporation.]
frusemide, paracetamol syrup

Examination
• Evidence of fluid overload
• normal or full volume pulses
• Normal or raised BP (HTN)
• Features of heart failure
• Headache
• Convulsion
• Palor
• Acidotic breathing
 Post-(obstructive) renal cause
History
• Poor urinary stream,
• straining,
• Abdominal pain,
• Dribbling,
• Dysuria,
• Haematuria
• (Acute neuropathic bladder)
• Spina bifida
• spinal tumours
• Spinal trauma,
• transverse myelitis,
Examination
• Large palpable bladder
• Features of urosepsis
• Obvious spinal lesion
• Neurological deficit

Evaluation Laboratory Investigations Renal Function

• E & U & Cr • Technitium-99m DMSA
• Urinalysis, (Dimercaptosuccinic acid) Scan for
• Urine m/c/s detecting renal parenchymal
• FBC, peripheral film scarring
• Bf for mp • DTPA (Diethylene triamine
• Blood culture pentacetic acid) for assessing renal
• Abd USS: KUB plasma flow.
• CXray • Technitium-labelled
• ECG Mercaptoacetyltriglycine (MAG3)–
• Others as appropriate e.g Hb Genotype, G6PD reflects proximal tubular excretion
screening, blood culture, stool mcs of isotope
• DTPA & MAG3 in dynamic
(CXray renography to rule out obstructive
ECG uropathy.
Others eg If patient haemolysing- Genotype, G6PD •
assay, Coombs test URAEMIC TOXINS
Suspecting Post Streptococcal Glomerulonephritis? • Urea
ASOT, Throat swab mcs, Skin swab mcs, Serum C3, • Creatinine
C4, Anti DNAse b, Hyaluronidase • Guanidine
Other investigations as necessary) • PTH Pertubation in the extra
cellular and intracellular Ca 2+
SUMMARY OF URINARY INDICES IN OLIGURIC RENAL levels which result in toxicity.
FAILURE - Middle molecules
- Polypeptides (Mol wt 500
– 500,000 daltons) thought to cross
the peritoneal membrane more efficiently
and removed more effectively than by
using cuprophan membranes in
haemodialysis.

Management of Pre- renal AKI:.

• Hypovolaemic shock and/ or severely dehydrated
– I.V. N/saline/Ringer’s lactate 20-30
mls/kg over 30mins to 1 hour
– Frequently re assess fluid volume status
and urine output
– Repeat boluses of N/saline up to about
60-80 mls/Kg PRN
• If patient remains in shock after
boluses consider septicaemic,
 cardiogenic or refractory shock
• No improvement in urine output
after restoring the circulation:
– i.v frusemide 2mg/kg (diuretic
challenge)
– If urine output remains inadequate
manage as intrinsic renal AKI
• Normal urine output after restoring circulatory
volume± diuretics
– Maintain careful fluid balance
– Consider or rule out the diagnosis of non
oliguric acute kidney injury

Management of Post-renal AKI:

• Prompt relief of urinary tract obstruction
– e.g need to pass a urinary catheter or
small sized NG tube for patients with
PUV
– Management for UTI, Sepsis, fluid
resuscitation as necessary

• Surgical consult Investigations

• Group I (To assess severity of CRF)
FBC
Fluid management: Intrinsic Renal failure Biochemistry-u&e+cr,
• Euvolaemic : • Calcium, P04,
 300-400mls/m2/day insensible Alkaline
loss + previous day’s fluid output phosphatase,
• Hypervolaemic- Albumin
 fluid restriction+ dialysis ± • GFR
diuretics* • PTH
• X-ray of hand and
• Fluid Composition: wrist to assess
 – Give K+ free fluids bone age and
– Composition of fluids may need to be features of
adjusted based on E & U osteodystrophy
• CXR
[Assess intravascular volume by using blood pressure, • ECG, Echo
heart rate, carpillary refill, skin turgor • Group 2 (To find the underlying
, replace urine output ml for ml. Replace any excessive cause of CRF)
losses in stool, e,g diarrhoea or from skin and • Renal USS, MCUG,
respiratory system as in hyperthermia. DMSA
Ongoing fluid therapy based on • Urinalysis + m/c/s
daily weights, • Immunology c3, c4,
blood pressure, ANF, DSDNA, ANCA
accurate fluid input and output records, • Renal biopsy
physical examination • White cell cystine
nutritional needs of the child • oxalate excretion
Note- Watch out for diuretic phase.]

management
• Pre-terminal
• Objectives are:
-To make the child feel normal and be
seen to be normal by mates
-Slowing progression to ESRF
-Maintain normal growth
-Preserving normal family milieu
-Prepare family for mx of ESRF
• Team
-Nephrologist, Specialist Nurse,
Dietician, Social Worker,
Psychologist/Psychiatrist, Teacher, Play
specialist
• GROWTH: Majority usually growth
failure prior to presentation
 -Find out why child is not growing
-Use of recombinant GH 0.9 iu/week
• NUTRITION
-Ensure adequate calorie intake 100-
120kcal/kg
-Protein and phosphate restriction
• FLUID AND ELECTROLYTE BALANCE
• METABOLIC ACIDOSIS: To ensure
adequate growth and prevent
demineralization of bone
- p.o NaHCO3 at 2mmol/kg

• BONE (Renal osteodystrophy)

-Use of phosphate binder Calcium
carbonate
-1,25-dihydroxycholecalciferol
0.02microgram/kg/day, titrate with PTH

HYPERTENSION
• Diuretics
• ACEI
• Nephrectomy

ANAEMIA
• Ensure adequate iron and folate
store
• Use of EPO 50iu/kg 3x/week

ESRD Mx
• RRT initiated when GFR
<10ml/min/1.73m2
• Other indications as enumerated
 in ARF
• Poor growth unresponsive to
conservative mx
• RRT
• PD, CCPD or CAPD
• Haemodialysis
• Renal transplantation

PROGNOSIS
• improved in the last 25 years in
developed countries
• ESRF is still a death sentence for a
Nigerian child.

We therefore have to concentrate on

preventive nephrology.

The predisposing factors like hypertension

and diabetes should be focused on.

The incidence of hypertension in our

Nation is about 12% while that of Diabetes
is 2% and fast increasing.

Metabolic Acidosis
 Severe acidosis
 i.v or oral sodium bicarbonate,
 Dialysis therapy
 NaHCO3 at 0.5-1.0 meq/kg over approximately 1
hour

 [Because the kidney excretes net acids generated

by diet and intermediary metabolism, acidosis is
 very common in AKI.
 Severe acidosis can be treated with intravenous
or oral sodium bicarbonate, oral sodium citrate
solutions, and/or dialysis therapy
 Consider Serum calcium level
 Base therapy at 0.5-1.0 meq/kg over
approximately 1 hour reasonable]

Hyponatraemia
 Usually dilutional
 Fluid restriction,
 If serum Na <120mEq/L correction to a
level of approximately 125 mEq/L with
hypertonic saline solution over several
hours.
 Dialysis
[If patient hyponatraemic and fluid depleted e.g in
background salt loosing states, restore fluid volume with
appropriate fluid.]

Mgt of hypocalcaemia & hyperphosphataemia

• Severe hypocalcaemia/symptomatic
hypocalcaemia
– i.v 10% calcium gluconate (dil. in 5%
D/W; 1 in 4) 1ml/kg up to a max.of 10
mls
• Given slowly over 30 minutes
under ECG monitoring or
auscultation for the heart rate
• Oral Ca supplements
– Consider serum
phosphate to avoid
metastatic CaPO4
deposition
 – Hyperphosphataemia
– Oral Calcium carbonate
– Aluminium containing compounds should
be avoided if possible
[Hyperphosphataemia is a very common electrolyte
abnormality noted in AKI]

Hypertension
• Diuretics
• Oral long acting agents e.g Calcium channel
blockers p.o Nifedipine
• ACE inhibitors should be used with caution and
watch out for hyperkalaemia.
• Consider dialysis.

[May be due to volume overload or alterations in

vascular tone.
If related to volume overload- diuretics or patient may
require dialysis.
Diuretics
Severe hypertension with hypertensive encephalopathy:
I.V Nicardipine, labetalol, or sodium nitropruside; I.V
hydrallazine or sublingual Nifedipine
Oral long acting agents
ACE inhibitors should be used with caution and watch
out for hyperkalaemia.
Patient may require dialysis.]

Nutrition
• Protein – Appropriate maintenance
requirements.
• Low phosphorus, low potassium food
• Maintenance calories (e.g120kcal/kg/day )
– infants, older children to receive
 appropriate calories or higher if needed
due to catabolic state or malnutrition)
• Dialysis if nutritional rehabilitation worsens fluid
balance

 [AKI associated with severe anorexia and

malnutrition can develop rapidly
 ?worsening azotaemia with increased muscle
break down and catabolism (check)]

Treatment of underlying illness

• Malaria
– Treat as for severe malaria
• Septicaemia
– Parenteral antibiotics e.g iv Cefuroxime
or I.V ceftriaxone

Prescribing Medications
 Drugs metabolised or excreted in the kidneys
 Adjust dose based on renal fxn.
 Drug adjustments table
 Avoid nephrotoxic drugs otherwise
 Adjust dose base on renal fxn
 Monitor
 drug levels
 potential adverse effects
Dialysis
•Dialysis: Early Initiation and not when patient is
moribund
Peritoneal dialysis
Haemodialysis
Continuous veno-venous haemofiltration/
Continuous arterio-venous haemo-filtration

INDICATIONS FOR DIALYSIS

• Symptomatic uraemia
- Encephalopathy
- Pericarditis
- Bleeding
- Pulm oedema

• Fluid overload
• To deliver calories
• Electrolyte imbalance not responding to
conservative treatment
Renal replacement therapy in AKI

COMPARISON OF PD, IHD AND CRRT

Prognosis
• Factors associated with mortality in previous studies
include the following
– Aetiology of AKI.
– Lack of dialysis access
– Late presentation
– Hypotension & Requirement for vasopressor
– Fluid overload
– Need for dialysis
– Presence of multi-organ dysfunction

• Mortality: 24%-46.5%

Prevention of AKI
• . Prevention of AKI
– Prompt management of gastroenteritis-
ORS
– Fluid volume resuscitation
– Fluid challenge for pre renal oliguria or
azotaemia
– Haemoglobinuria
• Alkaline diuresis
– Removal of nephrotoxins

Drugs studied for prevention of AKI

• Renal-dose or low-dose dopamine
• Loop diuretics – may be useful for the control of
fluid status.
• Theophylline
• Urodilatin
• Fenoldopam
• Bicarbonate
• Atrial natriuretic peptide
None has been consistently and reproducibly shown to
be protective
[After haemodynamic resuscitation and removal of
nephrotoxins, no specific drug-based intervention has
been consistently and reproducibly shown to be
protective. The alleged nephroprotective effect of so-
called renal-dose or low-dose dopamine was refuted by
findings from a multicentre, randomised, double-blind
placebo-controlled trial.108 Loop diuretics might protect
the loop of Henle from ischaemia by decreasing its
transport-related workload. However, no results from
double-blind, randomised controlled studies of suitable
size have shown that these agents reduce the incidence
of acute kidney injury.109 The usefulness of diuretics
remains confined to the control of fluid status. Other
drugs such as theophylline,110 urodilatin,111
fenoldopam,110, 111 bicarbonate,72 and atrial
natriuretic peptide112 have been studied in different
subgroups of patients and clinical contexts. However,
such studies have been negative, too small, single centre,
confined to a very specific group of patients, or have not
yet been reproduced. Thus, no established
pharmacotherapy exists for acute kidney injury.]