HEAVY METAL NEPHROPATHY

Dr Anyamele Ibuchim
• INTRODUCTION
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• CLINICAL
PRESENTATION
• DIFFERENTIALS
• WORK UP
• TREATMENT
• PREVENTION
 Introduction

• Metals with relatively high

densities,atomic weights or
atomic number
• Criteria used vary,depending
on author and context
• Density Criteria: 5g/cm
• Other Criteria,such as Atomic
number{ >20},and Atomic
weight{>22.8 Na}.
• Examples include
Lead,Mercury,Cadmium,Chrom
ium,Cobalt etc
• Many of these metals are used in the
mining,smelting and construction
industries,as well as in agricultural
pesticides
• Also used in spray painting and
household paints,as well as fuel
additives{Lead}.
• Typically,those involved in the
affected industries are more exposed
• Also,Atmospheric exposure occurs
when these metals are released in the
atmosphere,as in the case of
combustion of leaded petrol
• Lead recognised as occupational hazard since 1839

• Apart from renal Toxicity,these metals can cause toxicities in

other organ-systems

• Usual route of entry is inhalation and ingestion

• Lead levels greater than 10mcg/dl have been
shown to have adverse outcomes in children
• 4 million households within the US have children
living within them that are being exposed to lead
• Elevated Blood Lead Concentration in Adults
>25mcg/dl
• In 2007,76.7% of increased blood levels due to
occupational exposure.
 EPIDEMIOLOGY

• Lead recognised as occupational exposure since 1839

• Epidemics of Lead poisoning in middle ages due to fortification of
wine and drinkimg beverages in lead glazed containers
• In electronics recycling,heavy metal toxicity is important in China
and South East Asia
• Availability of Leaded gasoline,paints,cosmetics and pipes in low
income countries suggest there's a significant if underrecognised
burden of toxicity
• Large scale epidemic of Lead poisoning reported in China in
2009,involving more than 2000 children living near smelting
plants
• Chronic Arsenic Toxicity endemic in Bangladesh and contiguous
areas of the indian subcontinent
• No sex predilection. Risk associated with occupational and other
exposure
• Children much more vulnerable
 PATHOPHYSIOLOGY

• The pathophysiology of heavy metal toxicities remain relatively

constant
• Heavy metals bind to oxygen,nitrogen and sulhydryl groups in
proteins,resultimg in alterations in enzymatic activity
• This affinity of metal species for sulhydryl groups serves a
protective role in heavy metal balance as well
• Body's primary defence against metal poisoning is to increase
synthesis of metal binding proteins
• Metalloproteins are induced by many metals
• They're rich in Thiol ligands,which allow high affinity binding with
cadmium,silver,copper and other metals
• Toxicity occurs when capacity of the metalloproteins is exceeded
• Some metals also compete with ionised species such as Ca and
Zn to move through membrane channels in the free ionic form
• Lead follows calcium pathways in the body,hence its deposition
in bone and gingiva
• In the kidneys,the primary damage is tubulointerstitial nephritis
• Presence of metals in the interstitium results in local activation of
epithelial,endothelial and interstitial fibroblastic cells
• This results in the expression of a variety of cytokines and growth
factors such as PDGF,TGF-B,which can contribute to
inflammation and fibrogenesis in the tubulointerstitial
compartment
• Humoral and complement mediated injury also plays a role
• The end result is a shrunken,fibrotic kidney without external
scarring
• Kidneys typically weigh less than 100g
 CLINICAL PRESENTATION

• Usually insidious,except in acute poisoning,when features of

acute intoxication are obvious
• Renal failure becomes apparent after years of exposure,and in the
case of lead,is associated with gout in up to half of cases
• Hypertension is also very common in lead nephropathy
• Other features of chronic renal insufficiency
• FANCONI SYNDROME due to tubular dysfunction
 DIFFERENTIALS

• Other causes of tubulointerstitial disease

• Analgesic nephropathy
• Balkan nephropathy
• Hypertensive nephroangiosclerosis
• Chronic pyelonephritis
 WORK UP

• Urinalysis,urine Microscopy
• E/U/Cr,Uric Acid
• FBC,Esr
• Renal Uss
• Renal Biopsy and histology
• Blood assay for the suspected metals
• Other ancillary investigations
• EDTA mobilization tests for lead. Xray fluoroscopy
 DIAGNOSIS

• Relevant history of occupational and other exposure risks

• Symptoms and signs of renal insufficiency
• Specific laboratory assays for the offending metal,as well as tests
of renal function
• Other necessary investigations
• Any patient with a history of repeated gout and hypertension
should be suspected of having lead nephropathy
 TREATMENT

• In the acute phase,chelation therapy.

• This usually resolves the interstitial disease
• In the chronic stage,general management of renal
failure,including renal replacement therapy for ESRD
 PREVENTION

• Limit occupational exposure

• Use of PPE
• Limitation of environmental pollution
• Removal of industries from residential areas
THANK YOU