Pigment nephropathy is acute kidney injury caused by the toxic effects of pigments like myoglobin, hemoglobin, and bile in the kidneys. It can result from rhabdomyolysis, hemolysis, or liver failure. The key aspects of management are aggressive fluid resuscitation to prevent hypoperfusion and the formation of tubular casts, as well as urine alkalinization to improve pigment solubility. Prompt treatment can help resolve the kidney injury if initiated early.

1. Pigment Nephropathy
Salwa Ibrahim MD FRCP
Cairo University
Navigate AKI Comprehensive Course
September 2018

2. Topics
• Definition
• Causes
1. Rhabdomylosis
2. Intravascular Hemolysis
3. Bile cast nephropathy

3. Introduction
• Pigment nephropathy is an
abrupt decline in renal
function as a result of the
toxic action of pigment on the
kidney
• It includes myoglobin,
released from skeletal muscle
in rhabdomyolysis,
hemoglobin, released during
intravascular hemolysis and
Bile cast nephropathy
induced by high serum
bilirubin levels

4. Rhabdomyolysis

5. Muscle injury leading to myoglobinuria was reported
in victims of WW II who died of uremia and
postmortem exam revealed extensive muscle necrosis
and pigment nephropathy

6. • Traumatic muscle injury: crush injury, grand mal seizure, electric
shock, prolonged coma
• Electrolyte disturbance: hypokalemia, hypophosphatemia
• Toxins and drugs: alcohol, statin, CsA, erthyromycin
• Infections: influenza and Varicella zoster
• Heat stroke and severe hypothermia
• Hypothyroidism
Rhabdomyolysis

7. Case
• 26-year-old female was admitted to with severe bilateral
thigh pain persisting for 5 days after heavy exercise
• On the physical examination, the bilateral thigh muscles
were tender and slightly swollen
• Blood work showed a raised CK level of 55235 U/L, ALT of
314 U/L , AST of 974 U/L (0–32), LDH of 1508 U/L (135–
214), and myoglobin of 3984 ng/mL
• Urine analysis, reddish with no RBCs

8. Pathogenesis

10. • Myoglobin, a heme pigment
present in the skeletal muscle,
is released upon injury
• Due to its small size, myoglobin
is readily filterable and is
excreted in urine

11. • Three basic mechanisms underlie myoglobin
toxicity
1. Renal hypoperfusion and vasoconstriction
2. Tubular cast formation causing tubular
obstruction
3. Direct myoglobin Induced nephrotoxicity

12. • Hyperphosphatemia can markedly potentiate ischemic
and nephrotoxic renal damage
• Hyperuricemia contributes to intratubular obstruction
• Hypovolemia is a crucial factor in development of
myoglobinuric ARF
• As much as 18 liters of fluid may extravagate into
damaged limbs
• The formation of thrombi in the glomerular capillary
tufts due to DIC be triggered in rhabdomyolysis.

13. Biochemical findings in rhabdomyolysis
1. Elevation of serum CK and LDH (>5000)
2. Myoglobin in urine
3. Hyperkalemia
4. Hypocalcemia
5. Hyperphosphatemia
6. High creatinine/BUN ratio
Serum CK begins to rise 2 to 12 hours following the onset of muscle injury and reaches
maximum within 24 to 72 hours

14. Fluid Resuscitation
• Expansion of extracellular volume is the
cornerstone of treatment
• Support of intravascular volume increases the
glomerular filtration rate and oxygen delivery
and dilutes myoglobin and other renal tubular
toxins

15. Management of rhabodomyloysis
• NSS should be infused at a rate of 1.5 liters per hour
• Urinary alkalization should be considered in patients
with acidemia and dehydration to achieve a urine pH
higher than 6.5-7.0
• Sodium bicarbonate is used with caution because it
may potentiate hypocalcemia

16. • The Renal Association Guideline 3.4-AKI*
advise fuid resuscitation with 0.9% sodium
chloride at a rate of 10-15ml/kg/hr to achieve
high urinary flow rates (>100ml/hr) with the
cautious addition of sodium bicarbonate 1.4%
to maintain urinary pH> 6.51

17. Mannitol
• An osmotic agent that causes shift of fluid from the interstitial
compartment leading to decreased muscular swelling and correcting
hypovolaemia
• A study by Bragadottir et al (2012) has shown that mannitol can
redistribute blood flow to the kidneys, induce renal vasodilatation and
increase renal blood flow by up to 61 %

18. • Dialysis may be needed
for hyperkalemia in the
oliguric phase and
hypercalcemia in the
diuretic phase
• Myoglobin, because of
size, is poorly removed
by hemofiltration or
peritoneal dialysis

19. HEME NEPHROPATHY

20. Massive intravascular hemolysis
• Paroxysysmal nocturnal hemoglobinuria (PNH)
• Hemolytic transfusion reactions as a result of ABO
incompatibility
• Mechanical damage to the erythrocytes during
cardiopulmonary bypass

21. Pathogenesis
• Free hemoglobin immediately
bound to haptoglobin and cleared
by hepatocytes by the formation of
bilirubin, iron, and amino acids
• If haptoglobin is saturated,
hemoglobin dimers accumulate in
the plasma and pass through the
glomerulus

22. Renal Biopsy
• ATN secondary to
haemosiderin
deposition

23. Management of Heme Nephropathy
• Volume repletion with NSS
• Alkaline Diuresis involves IV NaHCO3 with either mannitol or
loop diuretics
• The alkaline pH of urine promotes the solubility of pigments
and limits the formation of casts and crystals
• The aim is to reach a urine pH above 6.5

24. • Mannitol an osmolar diuretic acts by
improving renal perfusion, promoting
the excretion of heme, and iron and
decreasing the oxidative stress in the
PCT cells
• Furosemide prevents the accumulation
of pigments in DCT

25. Bile Cast Nephropathy

26. The association of hyperbilirubinemia and kidney failure was
first described in 1899

27. HRS

29. DD of AKI in liver Disease
• HRS
• Bile Cast Nephropathy
• ATN

30. Risk Factors
• The risk of acute tubular injury increases when
serum bilirubin levels are greater than 20 mg/dl
• Low serum albumin decrease binding of bile acid and
bilirubin to albumin allowing them to be filtered by
the glomeruli with subsequent increased tubular
exposure

31. Pathogenesis
• It causes oxidative damage
of tubular cell membrane
• It is caused by uncoupling
of mitochondrial
phosphorylation
deceasing ATPase activity
Greenish yellow discoloration of kidney with BCN

32. Pathology
Bile casts within tubular lumina with tubular epithelial injury
The tubules contain cellular debris and detached epithelial cells

33. Casts containing bilirubin
and bile salts in renal
tubules

34. Urine analysis
• Urinary sediment of epithelial cells containing
granular or crystalline bilirubin and bile stained casts

35. Management
• Bile cast nephropathy is
treated by treating the
liver injury (hydration, IV
albumin, ERCP+stent etc.)
• Albumin dialysis has
been used to remove bile
acids and bilirubin in liver
failure with mixed results

36. Prognosis
The kidney injury is reversible if bilirubin levels are
decreased early

37. • Recovery of renal function may take several
weeks depending on the extent of proximal
tubulopathy and bile cast formation

39. • AKI is a common complication of rhabdomyolysis
• Regular monitoring of renal function is necessary
• Once a diagnosis of rhabdo is made, patients should be
managed aggressively
• Aggressive fluid resuscitation for hypovolaemia; urine
alkalinisation to protect the kidneys from myoglobin;
mannitol to increase perfusion to the kidneys and decrease
muscle oedema

40. • The general goals for preventive therapy in heme
pigment-induced AKI are correcting volume depletion
and preventing intratubular cast formation
• There are two modalities that have been used
• Volume repletion with NSS
• Alkaline-mannitol diuresis

41. • Bile cast nephropathy is a rare entity caused by toxicity
from bile acids, obstruction from bile casts, and systemic
hypoperfusion
• Bile cast nephropathy may be under reported and should be
considered in the differential diagnosis of AKI in liver
disease
• Treatment is largely supportive directed to improving
cholestasis