ACUTE RENAL FAILURE.

BY
DR. KWAIFA, SALIHU IBRAHIM
(MBBS,MWACP, FMCP,FACP,FASN)

CONSULTANT
PHYSICIAN/NEPHROLOGIST
VISITING LECTURER, CHS, NILE
UNIVERSITY, FCTA ABUJA.
 ACUTE RENAL
FAILURE
• A rapid (over hrs to weeks) often reversible decline in glomerular
filtration rate accompanied by azotaemia and oliguria (though not
invariably)

Functionally:
• 3 fold rise in serum creatinine levels

or
• 75% reduction in GFR
• Urine output of <0.3ml/kg/hr for >24hrs or total anuria for 12hrs

or
• Serum creatinine level >353.6µmo/l following an acute rise of
44.2μmol/l
 Enormous Burden is Driven and
sustained by:
Low capacity of the healthcare system
• Community prevention
• Appropriate health seeking attitudes
• Availability & Accessibility of
healthcare facilities
• Prompt &Appropriate intervention
 MAGNITUDE
worldwide incidence
• 1-3% of all medical cases (Lamiere)
• Studies outside Africa = 1% of all patients
admitted to hospital

Africa
• Very few reports available
• Actual incidence not known
• 13-40% of admissions for kidney disease
(Nigeria, South Africa, Sudan Congo)
• 2% of total medical admissions (Ekwere, Nigeria)
 PECULIARITIES IN
PRESENTATION
• Delayed presentation
• Underlying chronic disease(10% of patients)
• Anaemia
• Multiplicity of factors :-
Infection/sepsis
Fluid & electrolyte loss
Nephrotoxins
Anaemia-malnutrition
Fluid overload– pulmonary oedema
 The nephron
Cortex

Vulnerability of the kidney

• Important blood flow

Medullary ray
(1/4 of cardiac output)
• High metabolic activity
• Largest endothelial surface
by weight
• Multiple enzyme systems
Outer
Stripe • Transcellular transport
Medulla

• Concentration of
Outer

Inner
substances
Stripe • Protein unbinding
• High O2
consumption/delivery ratio
in outer medulla

Inner
Medulla

1618
 ARF in the Developed World
⮚ Disease of the old : 72% over 70 yrs (Feest, 1993)
⮚ Cardiogenic shock, sepsis & Multi-organ failure in
ICUs
⮚ Increasing use of beneficial interventions in poor
risk patients – CABG, open heart surgery
⮚ Rising iatrogenic etiology - Nephrotoxic agents -
Aminoglycosides, ACE-I, Diuretics, Contrast
agents.
⮚ Consequences of traffic & industrial accidents, Tx
⮚ Mortality 50-70% in pts with Sepsis & Cardio-
pulmonary dysfunction – pts dying with ARF
 ARF in Developing
Countries
⮚ Pattern of ARF significantly different
⮚ Pattern may differ between various countries
⮚ Average age lower - Mean age 34 yrs in India
& 47 in S. Arabia (Chugh, 1998, Al-Homrany, 2003)

⮚ 60% cases in India due to diarrhoeal diseases,

malaria, leptospirosis, IV hemolysis, drugs &
chemicals & snakes & insects
⮚ 50% of ARF in Nigeria due to herbs (de Broe, 2005)
⮚ Estimated incidence 55 cases/m/yr in Thailand
(Indraprasit & Sakulsasngprapha, 1997)
Pattern of Acute Renal Failure in
3277 Patients at PGI,
Chandigarh

67% 11% 22%

55% 24% 21%

61% 30% 9%

64% 30% 6%

Chugh, Oxford Textbook of Clin. Neph., p. 1614,

 Medical Causes of ARF at Chandigarh

1965-74 1975-80 1981-86 1987-93 2000-04

(%) (%) (%) (%) (%)

Diarrhoea (Including HUS) 23 12 10 5 7

Hemolysis G-6-PD def. 12 12 6 4 4
Glomerulonephritis 11 9 9.5 11 15
Drugs & Chemicals 9 7 8 13 12
Sepsis 2 1 8 10 12
Transplant related 0 3 4 8 6
Snakes & Insects 3 3 2.5 2 3
Miscellaneous 7 8 13 11 9
%age of total ARF 67 55 61 64 68

Chugh et al. Oxford Textbook of Clinical Nephrology, 2

 Hospital Acquired ARF

Chandigarh Abha
India S. Arabia

Total admissions 29501 26000

No. with ARF 441 (1.49%) 150 (0.6%)
Community acquired ARF 251 (0.8%) 57 (0.25%)
Hospital acquired ARF 190 (0.64%) 93 (0.35%)

Jha & Chugh, 1992, Al Homrany,

2003
 Hospital Acquired ARF at
Chandigarh
: Pathogenetic Factors
Causes No. %age

Nephrotoxic Drugs 54 29
Contrast Media 8 4
Decreased Renal Perfusion 39 21
Major Surgery 35 18
Sepsis 33 17
Allograft Rejections 8 4
Hepato-renal 5 3
Miscellaneous 8 4
Total No. 190 100

Jha & Chugh, 1992

 Profile of ARF Associated with
Medical Diseases in Abha, Saudi
Arabia
Sepsis 24.7%
Pre-Renal 23.3%
Ischemic 12.7%
Rhabdomyolysis 10.7%
Drugs 7.3%
Glomerulonephritis 6.7%
Malaria 3.3%
Snake Bites 1.3%
Others 9%

Al-Homrany, East. Med. Health J. 91: 1061, 20

 Toxic Nephropathy – Iatrogenic
Etiology is Increasing

⮚Increasing use of more efficient

but more nephrotoxic agents
• Aminoglycosides
• Ace Inhibitors
• X-ray contrast media
• NSAIDS
• Diuretics
How Do the Drugs / Toxins Cause
ARF
⮚ Reduction in renal perfusion
• NSAIDS, ACE-I, CyA, Radiocontrasts, Ampho B, IL-2
⮚ Direct tubular toxicity
• Aminoglyc., Radiocontrasts, Ampho B, Methotrexate
⮚ Heme pigment induced tubular toxicity
• Lovastatin, Ethanol, Cocaine
⮚ Intratubular obstruction
• Acyclovir, Sulpha, Eth. glycol., Methotrexate
⮚ Allergic interstitial nephritis
• Penicilline, Cephalosp., Sulpha, Cipro, Frusemide
⮚ HUS (CyA, Tacro, Mitomycin, Quinine)
 Pathogenesis of Radiocontrast
Media Induced ARF (Update Aug. 2006)
⮚ Incidence around 15% - 1% require dialysis.
⮚ ARF begins within 12-24 hrs., non-oliguric
⮚ Risk of nephrotoxicity > with Ist generation
agents (1400-1800 mosm/kg) compared to low
osmol (500-850) & Iso-osmol (290).
⮚ Renal injury due to renal vasoconstriction and
direct cytotoxicity.
⮚ Pts. with S. creatinine >1.8, GFR<60, diabetics &
pts. with advanced heart failure at high risk.
CIN results in increased in-hospital & long term
mortality
 Ace Inhibitor Induced Functional
ARF
⮚ Frequent cause of drug associated ARF.
⮚ Common in B/L RAS, RAS in solitary kidney and
in elderly HT pts even without stenosis.
⮚ Suppression of vasoconst. effect on efferent
arterioles.
⮚ In Na depleted pts, rapid ↓ of vascular resistance.
⮚ Diuretics increase Na depletion & may be
contributory
⮚ Pre-existing small renal vessel disease in
diabetics facilitates ARF.
ARF due to Tropical Infections

⮚ Diarrhoeal Diseases including HUS

⮚ Falciparum malaria
⮚ Leptospirosis
⮚ Mucormycosis
⮚ Others - Meliodosis, Dengue,
Hanta virus, Tetanus
 ARF due to Diarrhoeal Diseases
(DD)
⮚ 5-10m deaths/yr in children in tropical countries.
⮚ Poverty, lack of clean water, inadequate med. help.
⮚ Acute Gastroenteritis accounts for 20%. Less
frequent causes are food poisoning & cholera.
⮚ 1/3rd are due to HUS associated with B. dysentery.
⮚ ARF in 90% of Chinese pts with E. coli enteritis
(Zhang, 2002)

⮚ 43% of pts. with DD are < 10 yrs of age.

 Hemolytic Uremic Syndrome

⮚ Commonest cause of Pediatric ARF : 35-40%

(Date, 1994)

⮚ Seen mainly in preschool age children.

⮚ Diarrheal prodrome usually mild and
unimpressive, may be absent in 30%.
⮚ Shigella commonest organism isolated.
⮚ Diagnosis – ARF with microangiopathic
hemolytic anaemia.
 Malaria - Epidemiological
Features
⮚ Endemic in 103 countries with a population
>2.5b.
⮚ 300-500 million cases/yr with 1-3 million deaths.
⮚ 90% deaths are in Africa.
⮚ P. falciparum in Africa, N. Guinea, Haiti, Indian
sub.
⮚ P. vivax in central America & Indian
subcontinent. Equally prevalent in S. America,
E. Asia & Oceana.
 Malarial ARF
⮚ Prevalence 1%; 2-5% in endemic areas (Zinna
99)

⮚ 4-15% of ARF in E. India (Prakash, 95, 03)

⮚ 25-30% of nonimmune visitors develop ARF
(Sitprija, 1988; Weber, 1991)

⮚ Non-oliguric in 50-75% (Zewdu, 1994)

⮚ Hemolysis (30.8%), Cholestatic jaundice

(23%), anaemia, thrombocytopenia in 2/3.
⮚ Usually hypercatabolic. Hyperkalemia
 Renal Histology in Malarial
ARF
⮚ ATN primarily involving distal
tubules.

⮚ Prox tubular casts loaded with

malarial pigment.

⮚ Glomerular lesions in 20%

⮚ Fibrin thrombi, pigment laden
macrophages.

⮚ IF – IgM and C3 in mesangium

(Boonpucknavig)

⮚ Enhanced expression of TNFα, IL-

Peritubular capillaries contain parasitized erythro
 Pathogenesis of ARF in Falciparum
Malaria
Unique properties of this parasite
⮚ Red cells more spherical, less deformable
⮚ Knobs on surface which extrude adhesive
protein PFEMP facilitating attachment to
receptors in endothelium
⮚ Release of cytokines
⮚ Intravascular hemolysis
⮚ Heavy parasitemia – hyperviscosity
Alteration in renal microcirculation
Renal ischemia
Specific Problems of Management of
Malarial ARF

⮚ More frequent dialysis as ARF

hypercatabolic
⮚ Peritoneal microcirculation impaired
⮚ HD vs PD - Slower correction of uremia and
↑ risk of death with PD (Phu, 2002).

⮚ Mortality 10-40% higher in those with severe

parasitemia, with multiple organ
involvement & in unimmunized subjects
 Acute Renal Failure in
Leptospirosis
⮚ Widespread zoonosis caused by L. interrogans.
Common in Thailand, S. America, India (Sitprija, 1980).

⮚ Wide range of animals harbor organisms in kidneys.

⮚ Organisms shed in urine survive in sewage or
drains.
⮚ Infection through direct contact or contamination.
⮚ Occu. hazard in coal miners, sewage & farm
workers.
⮚ Account for 24% of ARF in S-E Asia (Sitprija, 68; Lai, 82)
 Ideal conditions
Sewage/Drain 🡪
Stagnant water
Contamination

Neutral or slightly alkaline

pH
 Clinical Spectrum of Renal
Manifestaions
⮚ Severity determined by virulence of
leptospires, bacterial load & the host defence.
⮚ Subclinical form – mild proteinuria &
sediment, tubular dysfunction due to
inhibition of Na – K – ATPase with kaliuresis &
hypokalemia.
⮚ ARF occurs in 10% to 67% - majority
nonoliguric.
⮚ Severe ARF often hypercatabolic & associated
with hyperbilirubinemia, oligoanuria &
thrombocytopenia.
Visith & Kearkiat, 200
 Complications Associated with
Leptospirosis Related ARF
Maldova Madrid India Taiwan
⮚ ARF 100% 75% 76% 100%
⮚ Hemorrhagic diathesis 80% 58% 29% 33%
⮚ Hepatocellular damage 72% 92% 85% 83%
⮚ Respiratory failure 38% 30% NM 75%
(ARDS Pulmonary hemorrhage)
⮚ Circulatory failure 33% 33% NM -
⮚ Pancreatitis 25% 25% NM 33%
⮚ Rhabdomyolysis 5% 5% NM 33%
⮚ Hyperglyceridemia - 100% - -

Covic, Peces, MuthuS, Yang

 Renal Pathology in
Leptospirosis
⮚ All renal structures may be involved.
⮚ Basic lesion - interstitial disease with edema &
infilter.
⮚ Glomerular lesions – occasional mesangial
prolif.
⮚ Vasculitis with focal hemorrhages in acute
phase.
⮚ Invasion of tubular cells from peritubular
capillaries.
 Grossly enlarged kidney
showing parenchymal
hemorrhages

Tubules are dilated & show

Medulla showing diffuse
epithelial degeneration &
interstitial infiltration
necrosis with heme & bile casts
in lumina
 Schematic Drawing of Induction &
Signaling Through NFκβ in T.I. Disease due
to Leptospira
Leptospira OMP

Tubul
ar Activation of NFκβ binding of
Cell
DNA

Increased expression of iNOS*, MCP-1** & T

Cellular Injury
Cell
Recruitment
Inflammation
Tubulo Interstitial Disease
*Inducible nitric oxide, **Monocyte chemoattractant protein
 Investigations in Leptospirosis

⮚ Index of suspicion
⮚ Urinalysis, RFT, LFT
⮚ Demonstration of organism – Alkaline urine,
blood, CSF – growth takes upto 4 weeks
⮚ Serological tests detect Ab. during 2nd wk
⮚ Benchmark procedure – microagglutination test.
⮚ IgM specific dot enzyme – linked immunoassay
(dot ELISA) - specific.
⮚ Culture – time consuming
⮚ Detection of Ag. by PCR offers early diagnosis
 Pathogenesis of Renal Lesions –
Role of Direct Nephrotoxicity

Leptospira endotoxins cause renal

tubular dysfunction
• Downgrading of Na-K-ATPase & Aquaporin-5
in Proximal tubules, causes polyuria,
kaliurises & hypokalemia (Younes Ibrahim, 1995).
• Administration of leptospira OMP extract into
cultured tubular cells induces significant
nuclear DNA binding of NF κappa β
transcriptional factor activation (Young 2003).
 Renal Mucormycosis –
An Under Diagnosed Cause of ARF
⮚ Rare opportunistic infection by Zygomycete
fungi.
⮚ Vascular invasion causes infarction and
necrosis.
⮚ ARF in 18 pts. B/L renal involvement in 13
(Gupta, 99).
⮚ High fever, lumbar pain, pyuria.
⮚ USG & CT scan – enlarged kidneys with
perirenal collection and intrarenal abscesses
(Chugh, 92).

⮚ Mucor hyphae in aspirated material or at surgery.

 Glomerulonephritis Associated with ARF
(11%)
⮚ Presentation –
Acute/Rapidly progressive
⮚ Careful history, urinalysis
& immunological
parameters
⮚ Renal biopsy to distinguish
I.C. from Paucimmune GN.
⮚ Immunosuppressive
agents, Plasma exchange
or both may be needed
ARF Due to Plant Toxins

⮚ Medicinal herbs
Impila, Cats Claw
⮚ Chinese herbs
⮚ Common edible plants
Djenkol beans,
mushrooms
⮚ Ayurvedic medicines
 ARF Due to Medicinal Herbs

⮚ Prescribed by Witch doctors in Africa & Asia

⮚ Ignorance, poverty and faith in the healers

⮚ 18% of all poisoning and 85% of deaths due to
poisoning in Pretoria (Otieno, 1991)

⮚ 33% of ARF in S. Africa (Seedat, 78; Loventhal, 74;

Buchanan, 76)

⮚ In Nigeria, 60% of ARF due to herbs (de Broe, 2005)

⮚ Indian & Chinese herbal medicines
⮚ Incidence possibly higher than reported
 Callilepis Laureola (Impila) Poisoning

⮚ In South Africa, Zambia, Zaira, Zimbabwe

⮚ Extract taken orally / enema / douche for
fertility, STD, blood purification
⮚ Used by 50% population in Natal
⮚ Common cause of ARF in S. Africa
⮚ Abd. Pain, vomiting, hypoglycemia, jaundice,
ARF
⮚ Alkaloid “Atractyloside” confirmed in pts.
with poisoning (Laurens, 2001).
⮚ Has nephrotoxic & hypoglycemic effects.
⮚ Mortality 50%
 Mushroom Poisoning

⮚ <1% of all mushroom are toxic

⮚ Amanita phalloides (death cap) and A virosa
(destroying angel)
⮚ Grows in lawns, pastures, forests, on stumps,
trees
⮚ Picked up by the inexperienced & children
⮚ Poisoning following ingestion of 1-3 mush
⮚ Abd. cramps vomiting, diarrhoea, hepatic & ARF
⮚ ATN in majority. Mortality >50%
⮚ Dialysis & charcoal hemoperfusion helpful (McClain,
 Aetiology 1978 1986-1988
Aetiology of n % n %
ARF (1978, Medical 98 65 174 77
Nephrotoxins 53 35 46 20.4
1986-1988) Herbal 50 44
Non-herbal 3 4
Infections 28 17 89 30.1
Typhoid fever 5 18
E. Coli septicaemia 6 15
Pneumonia (various) - 14
Klebsiella pneumoniae 6 4
Malaria 2 9
Obstructive uropathy from Schistosomiasis 3 -
Septicaemia (culture negative) - 3
Acute pyelonephritis 2 1
Tetanus 2 1
Hepatitis virus 1 -
Acute bacterial endocarditis 1 -
Pseudonomas septicaemia - 1
Streptococcus pyogenes septicaemia - 2
Gastroenteritis 5 21
Other causes 12 29
Acute pancreatitis 2 3
Other causes 10 -
Seedat YK & Nathoo BC: Rhabdomyolysis - 12
Nephron 1993;64:198- No aetiological factor - 24
201
2577
 He
rb s

Twasa Medicinal plant seller in Abidjan

A.B. Cunningham. African Medicinal plants. People and Plants Working Paper, Unesco, March
1993
 He
rb
Callilepis laureola (Impila) s

• Zulu herbal remedy (Impila = “health”)

• Decoction made from root
• Administered orally or by enema
• Stomach complaints, cough, tape-worm
infestations, impotence, to induce labour
• Magical and protective powers (children)

The plant bears a tuberous potato-

similar root with characteristic
bulbous shape and pungent odour.
Photo: G. Nichols, Northern KwaZulu-Natal Aug-Nov yields solitary creamy
Popat A et al: Clin Biochem 34: 229-236, 2001 white flowers with a purple disc.
 The isolation of a storage organelle of atractyloside in He
rb
Callilepsis laureola s

• Herb - S.A. Zambia, Zaire,

Zimbabwe
• Orally - enema - multiple
applicatum
• Common cause of ARF in blacks
• Liver toxicity Kidney from
patient who
C. laureola is the primary site of
storage for atractyloside *in the died from ARF
cells of the tuber. due to
Callilepsis
laureola
(Impila)
(Bhoola K.D.N.,
* Hypoglycemic agent
PhD thesis,
Mitochondrial toxicity 1983)
opening of permeab.transition pores
release cytochrome C caspase activ.
Dehrmann FM et al: J Ethnopharmacol 34: 247-251, 1991
 Herbs and the Kidney: What to Beware Hof
erb
s
?
• Traditional medicine ‘Africa’
– Euphorbia matabalensis
– Callilepis laureola (Impila)
– Securidaca longepedunculata
– Aloe capsensis

• St. John’s Wort (CYP3A4-

inducer)
Hypericum perforatum Indavi
r
• plasma levels ↓↓:
– Cyclosporine
– HIV-1 protease inhibitors Indavir + St John’s
– Digoxin wort
– Theophylline
Piscitelli SC et al: Lancet 355: 547-548,
2000
 He
Takaout El Beldia rb s
Tamaris Orientalis

• Natural
• Plant
• No toxic
• Rare
• Black dye
hair

M. Benghanem
 He
Takaout Roumia rb s
Para-Phenylene Diamine

• C6H4(NH2)2
• Mineral
• High toxicity
• Free selling
• Black dye
hair
• Cosmetic
agent
• Films

M. Benghanem
 He
Poisoning with hair-dye containing paraphenylene diamine: s rb
ten years experience

Renal failure
• Acute:
– Ingestion
– Suicidal attempt
• Chronic:
– Skin contact
– Focal glomerulosclerosis

Suliman SM et al: Saudi J Kidney Dis Transplant 6: 286-289, 1995

 Ayurvedic Drugs Sold in USA found Toxic
by Harvard Researchers (Saper et al, JAMA, 2004)
Dangerous levels of lead, Hg, As in 14 of 70 Ayur.
drugs.
⮚ Baidyanath Stable’s - Mahayograj Guggulu, Makardwaj,
Swarna Mahayograj Guggulu,
⮚ Mahalaxmi’s - Vilas Ras ; Unjha’s – Navratna Rasa ; Navjivan’s
Balasugathi
⮚ Zandu’s – Maha Sudarshan Churna & Bala Guti ; Dabur’s –
Maha Sudarshan Churna ; Himalaya’s – Karela ; Hari Narayan
Pharmacies – Gesari ; Jalaram’s – Bal chamcha ; Syncom’s –
Shilajit
High levels of Lead, Mercury & Arsenic
⮚ Lead - Median 40ug/g Range 5-37000.
⮚ Mercury – Median 20-225ug/g Range 28-104,000
⮚ Arsenic – Median 430ug/g Range upto 8130
ARF Due to Animal Toxins

⮚ Viper snakes
⮚ Sea snakes
⮚ Stinging insects
⮚ Raw gall bladder
⮚ Bile of Carp and Sheep
 Snake Bite Induced ARF
⮚ Occupational hazard in the tropics.
⮚ In Asia alone, 4 million snake bites

Russell’s Viper
each year.
⮚ 50% are envenomed resulting in
100,000 annual deaths (Chippaux-Bull
WHO 1998).

⮚ Renal lesions in Viperidae,

Colubridae & Hydrophidae snakes.

Echis Carinatus
⮚ Majority follow Russell’s viper, Echis
carinatus (saw scaled viper)
⮚ 13-32% develop ARF.
Chugh KS, KI, 1989
 Clinical Features Following
Snake Bites

Site of Bite
⮚ Pain, swelling, ecchymosis, oozing.
⮚ Incoag. blood, I/V hemolysis, FDP urine.

⮚ Intense hypofibrinogenemia (+ve 20’

WBCT test)

⮚ ↓ factors V, X,XIIIA, protein C & anti-

thrombin C.

⮚ Sea snakes – Myonec., muscle pains,

weakness.
Pts may develop life threatening ↑K.
Chugh, KI, 1989
Pathogenesis – Renal Lesions

⮚ Direct nephrotoxicity due to release of

mediators like histamine, kinins,
eicosonoids, platelet activating factor,
Endothelin & catecholamines.
⮚ Hypovolemia
⮚ Hemolysis
⮚ Myoglobinuria
⮚ DIC
⮚ ATN in 70%, ACN 20-25% Chugh, KI, 1989
 ARF Due to Bee, Wasp & Hornet Stings

⮚ Vespids – Wasps, hornets & yellow jackets.

– Phospolipase A, Hylourindase, Antigen 5,
Kinin, Mastoparo
⮚ Apids – Honey bees
– Mellitin
⮚ Pathogenesis – Rhabdomylosis 51%,
– Hemolysis 49%
⮚ Histology – ATN
AIN 20%
24% have both
(Chao, 2003, Chugh 1976, Sakhuja 19
 ARF due to Other Animal &
Chemical Toxins

⮚ Scorpion & Spider stings cause DIC & bleeding

⮚ Jelly fish, Giant centipede cause I/V hemolysis
⮚ Enzymes in venoms may degrade extracellular
matrix molecules and lead to disruption of BM
architecture.
⮚ Mushroom poisoning
⮚ Copper Suphate, Ethylene bromide, Chromic
acid.
 Copper Sulphate Intoxication

⮚ Used in leather industry, cheap & freely

available.
⮚ Common mode of suicide in the poor in
India.
⮚ Accidental poisoning by ingestion of “holy
water” in Nigeria.
⮚ Nausea, vomiting, hematemesis, malena.
⮚ Jaundice, convulsions,
Chugh pancreatitis,
et al. 1977, 1998; Sontz & Schwerg
 Post-op / Surgical / Post-ischemic
ARF

⮚ Common following surgery or sepsis in pts.

with DM, atherosclerosis, malignancy & poor
nutrition.
⮚ Cardiac surgery
⮚ Correction of obstructive jaundice
⮚ Sepsis in multi organ dysfunction syndrome
(MODS)
⮚ Factors - activation of vaso-active hormones,
induction of nitric oxide synthetase, release of
cytokines and ↑ reactive O2 species, activation
 Obstetric Complications are still a
Major Cause of ARF in some
Countries
⮚ Prevalence of unsafe home delivery practices.
⮚ Clandestine abortions by untrained personnel.
⮚ First peak 8-12 wks, 2nd peak 34-36 wks (Chugh,
1998)

⮚ Euthopia 50% (Zewdu, 1994)

⮚ Argentina* 32% (Firmat, 1994)

⮚ Nigeria* 25% (Bambgboye, 1993)

⮚ India 6% (Chugh, 2003)

*Mortality 35-50% in developing countries.

ACN seen in about 25% of cases.
 Mortality in Acute Renal Failure

⮚ 7% in Pre-renal and 50-70% in Post-op.

ARF
⮚ 50-80% in pts with sepsis &
cardiopulmonary dysfunction
⮚ No significant decrease despite advances
⮚ Higher mortality in elderly population &
multi-organ failure
 Radiocontrast Media
Nephrotoxicity
⮚ Incidence 0.3-40% of patients exposed
⮚ Arteriography carries a higher risk
⮚ Lower toxicity with less ionic agents
⮚ Iodide induced ARF persists for 2-4 days
⮚ 1% of pts develop irreversible renal failure
⮚ Iodide induces hyperuricosuria, vascular
injury, interaction with Tamm-Horsfall protein
⮚ Less frequently hypersensitivity acute
interstitial nephritis
 Peculiar aetiological factors in our
environment
• Nephrotoxins
– Native herbs
– Drugs
• Cholera
• Septicaemia (Typhoid)
• Obstetric causes (APH, PPH, Septic Abortion, Eclampsia)
• CuSo4 (green water)
AETIOLOGIC FACTORS AMONG THE
DIFFERENT AGE GROUPS

Udo A, Arogundade FA et al, NAN Conference 2010

 Increase in Serum Creatinine

• Inhibition of tubular creatinine secretion

Trimethoprim, Cimetidine, Probenecid

• Interference with creatinine assays in the lab

(false elevation)
glucose, acetoacetate, ascorbic acid, cefoxitin
 Increase in Serum urea without AKI

• Increased production
GI Bleeding
Catabolic states
Corticosteroids
Protein loads
 Pathophysiology of ARF
• 3 major phases
– Initiation Phase
– Maintenance Phase
– Recovery Phase
 Clinical Course of ATN

• Initiation Phase (hours to days)

Continuous ischemic or toxic insult
Evolving renal injury
ATN is potentially preventable at this time
• Maintenance Phase (typically 1-2 wks)
Maybe prolonged to 1-12 months
Established renal injury
GFR < 10 cc/min, The lowest UOP
• Recovery Phase
Gradual increase in UOP toward post-ATN diuresis
Gradual fall in SCr (may lag behind the onset of diuresis
by several days)
Bellomo R et al Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome
measures, animal models, fluid therapy and information technology needs: the Second International
Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004
Aug;8(4):R204-12.
 • Acute kidney injury (AKI) is defined as abrupt clinical and/ or
laboratory manifestation of abnormal kidney function within
48 hours of kidney injury.
• A reduction in urine output documented as less than 0.5
ml/kg/hour for more than 6 hours.
• Absolute increase in serum creatinine of more than or equal
to 0.3 mg/di (26.4 umol/L) or a percentage increase in serum
creatinine of more than or equal to 50% (1.5 fold from
baseline).
• The term AKI was introduced by the International
Consensus Conference on Acute Dialysis Quality Initiative
(ADQI) workgroup [Critical Care 2004] in place of the highly
restrictive and commonly used term, acute renal failure
(ARF).

Mehta R et al Acute Kidney Injury Network Report. Crit Care. 2007 Aug;11:R31.
 Epidemiology
• Medical wards about 5% of medical
admissions

• ICU: 5-30% of ICU admissions

n ≈ 30,000 ICU pts, 53 centres, 23 Countries AKI ≈ 2000
 Classification
• Urine Volume
• Medical Specialty
• Aetiological classification
 AR
F

Specialt
Urine Volume Aetiological
y

Medic Surgic Obstetric or

al al Gynae
Oligur
Non-oliguric ICU
ic
Renal / Post -
Pre- renal Intrinsic renal
 Aetiologica
l

Renal /
Pre- renal Post -
Intrinsic
renal

• Hypotension •• Vascular
Intra ureteral obstruction
• Hypovolaemia • • Renal infarction,
Stones, RAS, RVT
Clots, crystals, tumour, papillae etc
• Fluid Loss – Renal loss, Extrarenal • • Malignant HT, Scleroderma,
Extra ureteral obstruction Atheroemboli
• Blood Loss – RTA, Perforation/rupture, APH, • Tubular
• Tumour
PPH • • Ischaemic eg Sepsis, Prolonged pre renal, Hypo T
RPF
• Poor Pump Function • •
ProstateNephrotoxic eg Aminoglycosides, myoglobin, Hb,
• Cadiogenic Shock • chemotherapy
BPH, Ca, Prostatitis
• CCF •• Glomerular
Urinary Bladder
• Pericardial effusion with tamponade • • Ca,
AGN Stones, Clots,
• Haemodynamic • •
Urethra Vasculitis
• Contrast Neph • • Stricture,
Thrombotic
Ca, microangiopathy
stones
• Prostaglandin Inhibition (NSAIDs) • Pre Eclamptic Toxaemia
• Other Drugs eg CyA, Tac, ACE Inhibitors • Interstitium
• HRS • Drug induced TIN
• Tumour infilteration
 AR
F

Specialt
Urine Volume Aetiological
y

Medic Surgic Obstetric or

al al Gynae
Oligur
Non-oliguric ICU
ic
• Hypotension Renal or Post -
• Hypovolaemia Pre- renal Intrinsic
• Fluid Loss
renal
• Blood Loss
• Vascular • Intra ureteral obstruction
• Renal infarction, RAS, RVT • Stones, Clots, crystals,
• Poor Pump Function • Malignant HT,
• Cadiogenic Shock • Tubular
tumour, papillae etc
• CCF • Ischaemic • Extra ureteral obstruction
• Pericardial effusion • Nephrotoxic • Tumour
• Haemodynamic
• Glomerular • RPF
• AGN • Prostate
• Contrast Neph • Vasculitis
• Prostaglandin Inhibition •
• BPH, Ca, Prostatitis
Thrombotic microangiopathy
• CyA, Tac, ACE • Pre Eclamptic Toxaemia • Urinary Bladder
Inhibitors • Interstitium • Ca, Stones, Clots,
• HRS
• Drug induced TIN • Urethra
• Tumour infilteration • Stricture, Ca, stones
 Peculiar aetiological factors in our
environment
• Nephrotoxins
– Native herbs
– Drugs
• Cholera
• Septicaemia
• CuSo4 (green water)
 Maintenance of renal auto-regulation

• Renin Angiotensin Activation

• Kinnin – kinninogen
• Renal prostaglandins
• Sympatho-adrenal activation
 Mechanism of RAS Activation
Salt & water
Angiotens ret.
inogen Va
soc
REN on
IN str t
icti aldos
ACE, Chymase, on
Cathepsins,
Angiote Peptidases

nsin I Angiote
nsin II

Intra renal
Events
 Intra renal events after RAS Activation

Angiotensi TNFR1
n II TNFR2
AT
+
recep

Angiotens
inogen NF-kB TNF-α

Profibrotic
Matrix
cytokines Tubula
Prolifer. & Chem attr &
Different.
synth
r cells Adhes Prot

FIBROSIS Inflamm
atn.
 Pathways Leading to AKI
Nephrotoxi
ns Hypovola
Renal Structural
emia
Growth factor Proteins
and
cytokine Renal Perf
activation
Proteinuri
Tubular a
Influx of Infl damage
Transdifferenti cells Lipid
ation of Obstructiv peroxidation
Renal Cells to e
GFR
fibroblast Uropathy
phenotype

Acute Renal
Kidney Microvascular
Inflammation
Injury Injury
/ Failure

Uraemia Oedema Acidosis Others eg Anaemia,

Ca X PO bal
 Clinical features
• Oliguria
• Uraemia
– GIT
– Heart
– CNS
– Haematological
– Dermatology
• Oedema
 Investigations
• Urine volume / microscopy
• Urinalysis
• Urinary electrolytes
• Serum chemistry eg creatinine, urea, K
• Haematology including serology
• Imaging eg USS, IVU, RUCG etc
• Renal biopsy
 Distinguishing the different causes of AKI

Type Urinalysis Urine SG Urine U Na FE Na Fe UN BUN/Cr

Micro (Mmol (%) (%) ratio
/L)

Pre-Renal Normal High hyaline < 20 <1 ≤ 35 >20:1

A.T.N Normal Low Muddy > 40 >1 > 50 ≤ 20:1

brown
Vascular Normal Normal Haematur > 20 Variabl
ia e
G.N Proteinuria Normal Haemat / < 20 <1
RBC
casts
TIN Mild prot WBCs / > 20 >1
casts /
Eosino.
Post Renal Normal Normal WBcs, > 20 Variabl ≥ 20:1
RBcs, e
granular
casts
Distinguishing Acute KI from Chronic KD
Parameters AKI CKD

Duration Short Prolonged

BP Normal High
PCV or Hb * Low Low
Urine Vol Low / Nil Normal or Increased
Serum K * Normal / High Normal / High
Serum Urea Very high High
Serum Creatinine * High High
Carbamylate Hb Low High
Fingernail Creatinine Low High
Kidney Size Normal or Increased Reduced

* - Could not distinguish between the 2

conditions
Sanusi AA, Arogundade FA et al AJNT 2008 ;1:21-26.
GRADING AKI
ed

Bellomo R et al Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome
measures, animal models, fluid therapy and information technology needs: the Second International
Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004
Aug;8(4):R204-12.
 RIFLE Criteria for Acute Renal Dysfunction

Category GFR Criteria Urine Output (UO)

Criteria

Risk Increased creatinine UO < 0.5ml/kg/h x 6 High

x1.5 or GFR decrease hr Sensitivity
> 25%
Injury Increased creatinine UO < 0.5ml/kg/h x 12
x2 or GFR decrease > hr High
50% Specificity
Failure Increase creatinine UO < 0.3ml/kg/h x 24
x3 or GFR decrease > hr or Anuria x 12 hrs
75%
Loss Persistent ARF = complete loss of kidney
function > 4 weeks

ESKD End Stage Kidney Disease (> 3 months)

AKIN STAGING
• Stage 1: rise in serum creatinine (Scr) by >0.3 mg/dL (26.4
µmol/L) or an increase of >150-200 % (1.5-to 2-fold
increase) from baseline. OR Less than 0.5ml/kg/hr for
more than 6 Hours.

• Stage 2: rise in serum creatinine by >200-300 % (2-to 3-

fold increase) from baseline OR Less than 0.5ml/kg/hr for
more than 12 Hours.

• Stage 3: rise in serum creatinine to >300 % (> 3-fold) from

baseline or serum creatinine ≥4.0 mg/dL (≥354 µmol/L)
with an acute rise of at least 0.5 mg/dL (44 µmol/L) OR
Less than 0.3ml/kg/hr for 24 Hours or anuria.

Only one criterion (creatinine or urine output) needs to be fulfilled to qualify

for a stage.aPatients who receive renal replacement therapy are considered
to have met the criteria for Stage 3, irrespective of the stage that they are in
at the time of commencement of renal replacement therapy.
Mehta RL et al. (2007) Crit Care 11: R31.
 Diagnosing AKI
• History and Physical exam
• Detailed review of the chart, drugs administered,
procedures done, hemodynamics during the procedures.
• Urinalysis
SG, PH, protein, blood, crystals, infection
• Urine microscopy
casts, cells
• Urine lytes
• Renal imaging
US, Retrograde Pyelogram
• Markers of CKD
iPTH, size<9cm, anemia, high phosphate, low bicarb
• Renal biopsy
 Distinguishing the different causes of AKI
Type Urinalysis Urine SG Urine U Na FE Na Fe UN BUN/Cr
Micro (Mmol (%) (%) ratio
/L)

Pre-Renal Normal High hyaline < 20 <1 ≤ 35 >20:1

A.T.N Normal Low Muddy > 40 >1 > 50 ≤ 20:1

brown
Vascular Normal Normal Haematur > 20 Variabl
ia e
G.N Proteinuria Normal Haemat / < 20 <1
RBC
casts
TIN Mild prot WBCs / > 20 >1
casts /
Eosino.
Post Renal Normal Normal WBcs, > 20 Variabl ≥ 20:1
RBcs, e
granular
casts
 Limitations of FE Na
• Diagnostic accuracy of 80% in prerenal
AKI

• <1% in Na retention states, severe GMN,

rhabdomyolysis, contrast nephropathy.

• High in CKD, diuretic use, glycosuria

HYALINE CASTS
RENAL TUBULAR
EPITHELIAL CELL
CAST (“EPITHELIAL
CAST”)
THE URINE SEDIMENT IN ATN

RTECs and renal tubular Renal tubular epithelial

fragments cell casts
Scoring system based on granular casts and renal tubular epithelial cells

Parazella MA et al. Clin J Am Soc Nephrol 2008; 3:1615-19

 Scoring system and final diagnosis of
ATN

Score Odds ratio 95% CI

Score 2 vs 1 9.7 5.3-18.6

Score ≥2 vs 1 74 16.6-329.1
Likelihood ratio (LR) of ATN vs pre-renal azotemia on the
basis of the number of granular casts in urinary sediment

Granular LR for ATN LR for pre-

casts/hpf renal
0 0.23 4.35

1-5 2.97 0.34

6-10 9.68 0.1

Clin J Am Soc Nephrol 4:691-693, 2009

THE URINE SEDIMENT IN ATN

ATN due to
ATN due to ethylene glycol ATN due to
myoglobinuria indinavir
 Indications for renal biopsy in AKI

• Any evidence of glomerular disease

-nephrotic range proteinuria
-sub-nephrotic range proteinuria with haematuria
-RBC cast
• AKI not resolving in 6 weeks
• AKI in connective tissue disease
• AKI in renal allograft
• Determine the prognosis and chance of recovery of
renal function in dialysis dependent AKI.
• Whenever potential Bx result can change the
management or prognosis.
 Management of AKI
• Treat precipitating event / condition

• Conservative Management

• RRT
 AKI Management

Treat Primary
Conservative RRT
Condition

Fluid
Electrolytes Diet
Balance
Acut Continuo
Intermittent
e • CAP us
D
• SCUF
• CCP
D •
• APD • Intermittent PD CAVH
• AHD • CVVH
• Intermittent HD
• Intermittent HF • CAVHD
• SLED • CVVHD
• EDD
• CAVHDF
• CVVHDF
 Treatment Modalities for ARF on the ICU
Urea clearance [ml/min]

IHD
SLED
CRRT
time [h]
 Fluid Management
• Limit fluid intake to insensible loss
(500-1200mls/day)
• Replace volume of urine / other
documented losses in the previous 24
hours
• Avoid Potassium containing fluids
• Diuretics may be useful in pre-renal
ARF
 Electrolyte management
• Hyperkalaemia
• Biochemical confirmation
• ECG appearance
• Force K into cells
– Glucose-Insulin Infusion
– Glucose Infusion
• Antagonise K Effects on heart
– 10% Calcium gluconate
• Remove K from circulation
– Dialysis
– Ion exchange resin
 Diet and Calorie
• High calorie low protein in acute phase
• High calorie normal protein in recovery
phase
• Parenteral hyperalimentation may
become necessary in prolonged cases
 Indications for RRT
• Clinical
– Encephalopathy
– Pulmonary oedema
– Persistent GI symptoms
– Pericarditis
– Refractory oedema
– Uncontrolled HT
– Bleeding diathesis
 Indications for RRT
• Biochemical
▪ Hyperkalemia > 6.5mmol/l
▪ Bicarbonate < 12mmol/l
▪ Urea > 25 mmol/l
▪ Creatinine > 600micromol/l

• Features of hypercatabolism
▪ K+ rate of rise > 1mmol/day
▪ Urea rate of rise > 10 mmol/day
▪ Creatinine rate of rise >100micromol/day
 Choice of RRT in ARF
Indication Clinical condition Suggested
modality
Uncomplicated ARF Stable, non-catabolic IHD,PD
Stable, catabolic IHD
ARF + fluid overload Stable IHD, CRRT, SLED
Unstable CRRT, SLED
ARF + raised intracranial Stable and unstable CRRT
pressure
ARF + respiratory failure Stable SLED, CRRT
Unstable SLED, CRRT
Septic shock SLED, CRRT

ARDS Stable and Unstable SLED, CRRT

Electrolyte abnormalities IHD, SLED, CRRT

Drug overdose/poisoning IHD and/or CRRT

 CRRT vs SLED (Sustained low efficiency
dialysis)
• SLED became popular because of CRRT disadvantages:
– Expensive, continuous pt immobilization, need for specialized machines
and pre-mixed commercial solutions, and anticoagulation

• Only 2 small studies compared these 2 in

hemodynamically unstable pts with AKI

• They did not see significant differences in hemodynamic

parameters and solute clearance

• They did not look at any patient-relevant outcomes, so

the jury is still out there

Am J Kidney Dis 2004;43:342-349

J Artif Organs 2007;30:1083-1089
Am J Kidney Dis 2008;51:804-810
Overall conclusion on RRT modality benefit in AKI

• CRRT does not confer a survival advantage as

compared to IHD

• SLED may replace CRRT although there is no outcome

benefit study up to this date

• There is limited data regarding the ideal timing of RRT

initiation and the preferred mode of solute clearance

• No evidence to support a more intensive strategy of RRT

in the setting of AKI
 complications
• CCF
• Pulmonary edema
• Arrythmias
• Pericarditis
• Uraemic encephalopathy
• Infections >60%
• GI haemorrhage- 10-20%
• Seizures
• Paralytic ileus
 Advantages / Drawbacks of
CRRT
⮚ More precise fluid & metabolic control
in pts with decreased hemodynamic
stability due to sepsis and multi-organ
Failure (Mehta, 1994)
⮚ Enhanced Removal of Injurious
Cytokines
⮚ Administration of Unlimited Nutritional
Support
⮚ Need for Prolonged Anticoag. &
Surveillance
 Disadvantages of Continuous
Treatment

⮚ Need for 24 hr anticoagulation

⮚ High risk of infection with indwelling
catheters
⮚ Constant blood membrane contact
⮚ Difficulty in maintaining fluid balance
⮚ Demand for 24hr skilled nursing
 Newer Treatment modalities
Modulating Vasoconstriction
• Calcium channel antagonists
– eg Transplant, CyA exposure, Radiocontrast Nephropathy
• Dopamine – Not effective from studies
• ANP may initiate diuresis in oliguric patients
• Endothelin blockade
• Nitric oxide modulation
• N acetyl cysteine use
 Is there a role for Dopamine in prevention or
treatment of AKI in ICU setting?
Clinical Outcomes:
• No effect on mortality
• No effect on the need for or incidence of Renal
Replacement Therapy (RRT)

Renal Physiologic Outcomes:

• Diuretic effect and increased creatinine clearance on the
first day which was not significant on the following days.

Adverse effect:
• on the immune, respiratory, and endocrine system.

Ann Intern Med. 2005;142:510-524

ANZICS Clinical Trial Group. Lancet 2000;356:2139-2143
 Role of ANP analogues in AKI?

• 61 patients in 2 cardiothoracic ICU with post-op AKI

assigned to receive recombinent ANP (50ng/kg/min) or
placebo

• The need for RRT before day 21 after development of

AKI was significantly lower in ANP group (21% vs 47%)

• The need for RRT or death after day 21 was significantly

lower in ANP group (28% vs 57%)

Crit Care Med. 2004 Jun;32(6):1310-5

Is there a role for Fenoldopam in prevention or
treatment of AKI in ICU setting?

• Dopamine-1 receptor agonist, lack of Dopamine-2, and

alpha-1 receptor effect, make it a potentially safer drug
than Dopamine!

• Reduces in hospital mortality and the need for RRT in

AKI

• Reverses renal hypoperfusion more effectively than renal

dose Dopamine

• So far so good specially in cardiothoracic ICU patients,

awaiting more powered trials in other groups!
J Cardiothorac Vasc Anesth. 2008 Feb;22(1):23-6.
J Cardiothorac Vasc Anesth. 2007 Dec;21(6):847-50
Am J Kidney Dis. 2007 Jan;40(1):56-68
Crit Care Med. 2006 Mar;34(3):707-14
 Is there a role for diuretics in the treatment of
AKI in ICU setting?
• PICARD Study:
Cohort study of 552 pts in 4 UC hospitals:
Odds Ratio
In-hospital Mortality 1.77
Non-recovery of renal function 1.68

• Improved urine output and shorter duration of RRT (none

has clinical relevance in ICU pts)

• But diuretics continue to be used for volume control in

AKI in ICU setting!

JAMA. 2002 Nov 27;288(20):2547-53

Crit Care Resusc. 2007 Mar;9(1):60-8
 Prognosis

• The prognosis of patients with ARF is

directly related to the cause of renal
failure and, to a great extent, to the
duration of renal failure prior to
therapeutic intervention.

• The mortality rate vary greatly

between 50 and 90%.
Determinants of Mortality or Survival
• Age
• Aetiology
• Severity
• Other co-morbidities
• Pulmonary Oedema
• Abnormal urine sediment (mortality 74% vs 31%)
• Multiorgan failure
• Hypotension
• Use of RRT
• Dose of RRT
 KEY
1- Nephrotoxin induced ARF
2- Obstructive Uropathy
3- Gastroenteritis (Cholera & Food
Poisoning)
4- Septicaemia
5- Gastroenteritis & Nephrotoxin or Sepsis
6- Surgical/RTA/ Head Injury
7- Hepatorenal Syndrome

Arogundade FA et al. Central African Journal of Medicine 2009 (In Press)

 CHRONIC KIDNEY DISEASE
Definition

Kidney damage- with structural or

functional abnormalities
or
Persistent decline in GFR less than
60ml/1.73m2 for not less than 3 months
Has assumed epidemic proportion all over
the world

Also increasing – growth rate 5-8%

 K/DOQI
CKD Classification
Stage Description GFR

1 Kidney damage/normal GFR

>90ml/min
2 Mild renal insufficiency 89-60
3 Moderate renal insufficiency 59-30
4 Severe renal insufficiency 29-15
5 End Stage Kidney Failure <15

*
 CHRONIC KIDNEY DISEASE
CONT’D
Community incidence & prevalence unknown in most parts
of Africa

(i) lack of community based representative studies

(ii) Majority of patients seek healthcare outside of

hospital centres.

(iii) Inadequately developed hospital & national

registries
 CKD (cont’d)
Few (very few) reliable community based
epidemiological studies

Congo 12.4 %**(recent, well conducted study)

USA 11.0%
Beijing 13%
Australia 14.0%
 Aetiology of chronic kidney failure in some African
countries
Aetiology of ESRD Nigeria Ghana34 Senegal 35 South Africa Libya36
(SADTR,
2000)
Hypertension (%) 30 - 40 48.7 25 21 10.5
Glomerulonephritis 25 - 30 42.3 16 23 8.0
(%)
Diabetes mellitus 3–5 20.7 27.4
(%)
Obstructive 4–5
uropathy (%)
Unknown (%) 15 – 20 34.2 30.6

Interstitial nephritis 6.4

(%)
Others (%) 3-5 4
 HYPERTENSION
Hypertension –An important Public Health Concern

• Prevalence highest, severity and consequences in

blacks – enormous!

• Genetic predisposition, High salt intake, Low birth

wt, Oligonephromegaly, poor/lack of control,
Asssociated renal risk factors-GN, Nephrotoxins,

Hypertensive Nephrosclerosis
• Accounts for 30-50% of CRF in Africa
• West Africa 30- 50%
• North Africa 5-21%
• South Africa 4.3%, 13.6%, 34.6%(Blacks/Indians/White)
PRINCIPAL CAUSES OF CHRONIC KIDNEY DISEASE IN NORTH AFRICA

Disease Percentage

Interstitial nephritis 14 – 32

Glomerulonephritis 11 – 24

Diabetes 5 – 20

Nephrosclerosis 5 – 21

Polycystic and other hereditary diseases <5

 CHRONIC GLOMERULONEPHRITIS

• A leading cause of CKD in Africa

• Accounts for 25 -60 % of CKD

Usually associated with infections

Bacteria –post streptococcal infections
Parasites ( well characterised)
Malaria –P.malariae
Filariasis ( Loa loa, O. volvulus)
Schistosomiasis( mansonia, haematobium)
Leshmaniasis ( viscera)
Viruses ( Hepatitis B,C; HIV)
 CHRONIC GN (CONT’D)
Presentation:
Commonly as Nephrotic syndrome
Peak age 5-8yrs; younger adults
Accounts for 0.5 – 2.5% medical admissions
(Zimbabwe, SA, Uganda, Nigeria)
Up to 20% as CRF
Asymptomatic Proteinuria( ?? proportion!!!)
Progression to ESRD in 3-7years
Poor response to treatment
Identification of parasitic antigens in a small
proportion
Figure Showing Quartan Malarial Nephropathy. P malariae GN:
PAS stainning of the glomerulus showing focal segmental sclerosis (in an 8-
year old child).
P malariae GN with glomerulus showing non uniform thickening of the gl.
capillary wall with splitting in places, sparse mesangial cellularity
& matricial expansion (Masson Trichome stain).
Filarial Loa Loa in urine film
Microfilaria within Glomerulus with thickening of glomerular
capillary wall and hypercellularity (Mixed membranous and
proliferative GN
Microfilaria in the interstitium, adjacent to it is
the glomerulus showing hyper cellularity
Cross section of MF within glomerulus showing features of
focal (Proliferative) GN
 Microfilaria in the tubules

Akinsola A et al. Loiasis and glomerulonephritis. Report of two cases and review of
literature.
 SCHISTOSOMAL NEPHROPATY

Mesangial proliferation with areas of mesangiocapillary changes

SCHISTOSOMAL NEPHROPATY

Focal and segmental glomerulosclerosis

 BURDEN OF HIV/AIDS IN SUB-SAHARAN AFRICA

Adults & Children living with HIV/AIDS 22.0m

Adults & Children newly infected 1.9
Adults Prevalence 5%
 HIVAN
• HIVAN is the commonest form of CKD in HIV Infection
• True magnitude unknown
• Frequency of Proteinuria or Abnormal GFR in HIV
patients is variable

Country Freq
South Africa 6%
Kenya 25%
Cote d’Ivoire 26%
Tanzania 28%
Zambia 33.5%
Uganda 20-48%
Nigeria 38%

◆Estimated HIVAN Population is about 1-3.5 million

black Africans. A huge epidemic!
HIVAN HISTOLOGICAL FEATURES

4
2 5

1. Collapsing glomerulo-sclerosis (Segmental)

2. Bowman’s Space Dilatation
3. Tubular Atrophy
4. Proteineous material in tubule
5. Interstitial Infiltrates
 DRUGS/NEPHROTOXINS
• Analgesics- (South Africa – 30% of CRF)
- (undefined in other parts of Africa)

• Herbal remedies: magnitude presumably

higher but nature of remedies not defined

• Chemical agents: Hg (Skin lightening cream)

• Environmental Pollutants- Hydrocarbons

(petroleum), Lead
 Hydrocarbon (HC) Exposure and
Glomerulonephritis (GN)
• Evidence for HC exposure and GN is mounting,
though remains slim

• Nigeria is the 7th world leader in petroleum

resources

• Increasing oil prospecting in West Africa and other

parts of Africa

• Exposure to petroleum is uncontrolled

• possible role for HC exposure in the expanding

pool of GN patients
 DIABETIC NEPHROPATHY
DM varies from 1 to 13% in Africa
The population of DM expected to double in
Year 2025: 10.8m 🡪 18.7m

• Zambia 23.8%
• South Africa 14-16%
• Egypt 12.4%
• Sudan 9%
• Ethiopia 6.1%
• West Africa 2-3%

Amos et al (1997). Diabetic Medicine

 RENAL REPLACEMENT THERAPY

• HD, CAPD, RTx

Availability of all the 3 modalities variable.. Some
not available at all in most countries!!

Accessibility to RRT very limited

Tropical Africa contributes <10% of world’s

total HD population of 1.6 m

HD costs more in Africa than rest of the

world!!
 ASSESSMENT OF PATIENTS for
Dialysis.
• Early referral ideal.
• Patients requiring dialysis within 3mths
of referral to a Nephrologist at greater
risk of morbidity and mortality than
those on longer term specialist care.
• Ensure any co-morbid factors are
identified and managed appropriately.

*
 ADVANTAGES OF EARLY
REFERRAL
• Ability to slow rate of • Most appropriate
progression. modality can be
• Control of BP and lipids chosen.
reduces CVS risk • Access can be planned.
thereby reducing co- • Pre-dialysis EPO.
morbidity load. • Increases compliance.
• HBV vaccine started • Dialysis commenced
early pre-dialysis. early with better long
• Patient education on term outcome.
dialysis. • Pre-emptive
transplantation.
*
 HAEMODIALYSIS VERSUS
PD.
• Selection of modality should be driven
by patients choice.
• Medical or social contraindications may
also influence choice.
• Resource availability also influences
choice.
• Cost also a major consideration.

*
 DIALYSIS PRESCRIPTION IN ARF AND
CRF
• Differ significantly.
• HD and other continuous therapies
favored in ARF.
• PD use in ARF declining.
• Maintenance HD and continuous PD are
modalities used in CRF or ESRD.

*
CONTRAINDICATIONS TO HD OR PD.

PD contraindications. HD contraindications.
• Colostomy/ • Thrombosed central
ileostomy. veins.
• Intra-abdominal • Severe angina.
adhesions. • Significant anemia.
• Hypotensive heart
• Very poor housing.
failure.
• Poor personal • Long distance from
hygiene. HD unit.
• Morbid obesity.

*
 INDICATIONS FOR DIALYSIS.
Clinical indications. Biochemical
• Grossly Uraemic indicators.
vomiting e.t.c. • Urea rise > 50mg/dl
• Acute pulmonary in 24hrs.
oedema. • Urea >/= 200mg/dl.
• Uraemic • K+ >/= 6.5mmol/l.
pericarditis. • HCO3 < 14mmol/l.
• Uraemic • Creatinine >
encephalopathy. 12mg/dl.
• Onset of • GFR < 15mls/min.
malnutrition.
*
 CONSTRAINTS TO MAINTENANCE
HAEMODIALYSIS

High cost of machines

High maintenance cost
Poorly developed infrastructure
Dearth of trained personnel
Endemic infections (HepatitisB, C, HIV)
Cost of supportive treatment(epo,..)
 COMPLICATIONS OF
DIALYSIS
• ACUTE
• Hypotension
• Haemolysis
• Muscles Cramps
• Air embolism
• Dialyzer reactions/First use reactions
• Infections
• Dysequilibirum syndrome
 COMPLICATIONS (CONT’D)
• CHRONIC
• Dementia
• Amyloidosis
• Acquired Renal cysts
• ? Adenocarcinoma
 KIDNEY TRANSPLANTATION
Transplantation: refers to the
process of transfer of living cells,
tissues or organs from
one person or site (donor) to
another (recipient)
with the sole aim of maintaining the
functional integrity of the
transplanted cells or organs in the
recipient.
* KWAIFA S. I.
 There are different types of grafts

Isograft: refers to tissues or organs

transplanted between genetically
identical individuals eg identical
twins.
Allograft: is the organ transplanted
between individuals who are not
genetically identical but belong to the
same species.
A xenograft: is the graft between two
different species.
* KWAIFA S. I.
Autografts(autologous) : are tissues
transplanted from one site to
another in the same individual.

Orthotopic: transplantation is the

transplant from a site in the donor
to a similar site in the recipient.

Heterotopic transplantation: refers

to that to a different site in the
recipient.
* KWAIFA S. I.
 Renal Transplant Versus Dialysis.

Confers the best possible quality of life

and reduces the mortality risk in
ESRD.
Only viable option for most patients in
ESRD in developing countries.
Cost savings evident by the second
year post transplant compared with
dialysis.
Morbidity and graft loss much less the
shorter the time on dialysis.
* KWAIFA S. I.
 Comparison of Average
Yearly Costs.
✹ Cost of 2ce weekly haemodialysis =
2,880,000:00.
✹ Cost 3ce weekly haemodialysis =
8,640,000:00.
✹ Cost of CAPD = 3,699,928:00.
✹ Cost of renal transplantation + immuno
suppressants for two years =
10,000,000:00.- PRIVATE
✹ 3,500,000.00-PUBLIC -AKTH
* KWAIFA S. I.
 Herrick twins and Joseph Murray.
December 23rd 1954.

* KWAIFA S. I.
TRANSPLANT TYPES
• Pre-emptic
• salvage

* KWAIFA S. I.
 DONORS
DECEASED (cadevaric)
Heart beating
Non-heart beating
Extended criteria
LIVING RELATED
Parents
Siblings
Offsprings

* KWAIFA S. I.
LIVING UNRELATED
Spouses
Distant relatives
Paired exchange
Non directed
Directed

* KWAIFA S. I.
* KWAIFA S. I.