CANCER AND THE KIDNEY

“Onco-nephrology”
Mortality according to GFR
 ACUTE KIDNEY INJURY
• The 1 Year risk of AKI ( defined as a rise in
Sr.Creat >50 %) in patients with cancer was
17.5%, with a 27% risk over 5 years.
Danish population-based study

• Distant metastasis = Higher risks of AKI

• Older population + dropping death rates
(higher risks and more comorbidities)
 Ca. with highest AKI risk
• Renal cell Ca.
• Multiple myeloma
• Liver carcinoma
• Lymphoma / leukaemia
• The high mortality rate among cancer pts.
with severe AKI – requiring dialysis - has
prompted some to question whether renal
replacement therapy should be offered at all.

• Available data suggest that cancer pts. With

AKI and Dialysis have SIMILAR mortality to pts
without cancer.
• Many cases doesn’t require long term chronic
dialysis
• The most frequently encountered AKI
syndromes in cancer pts.
• tumor lysis syndrome (TLS),
• cast nephropathy, and
• thrombotic microangiopathy
 Acute tumour lysis syndrome
• rapid destruction of a fast-growing, bulky, malignant mass
either spontaneously or following successful treatment.
• most common in high-grade hematologic malignancies, +
fast-growing solid tumors, such as testicular cancer
• Abrupt release of intracellular ions, proteins, and
metabolites result in rapid hyperuricemia, hyperkalemia,
hyperphosphatemia, hypocalcemia, and AKI.
• Keys to management : acute reduction of uric acid level
with nonrecombinant/recombinant urate oxidase;
hydration and possible alkalinization of urine
(controversial); and hemodialysis.
  Cast nephropathy
• Caused by two factors:
- formation of intratubular casts from precipitation of
free light chains in the tubular lumen
- and/or direct tubular toxicity of free light chains.

• Intratubular casts cause obstruction in both the proximal and

distal tubules.
• Clinical presentation : AKI
• Risk factors : hypovolemia, urinary pH lower than 7, sepsis,
and hypercalciuria.
• Keys to management: volume repletion with isotonic saline,
alkaline diuresis, treatment of hypercalcemia if present, and
consideration of plasma exchange (controversial).
 Thrombotic Microangiopathy (TMA)
• incidence ~ 5%.
• may be associated with the cancer itself : adenocarcinoma
of the stomach, breast, or lung + hematologic malignancies.
• Chemotherapeutic agents : bleomycin, cisplatin, cytosine
arabinoside, daunorubicin, deoxycoformycin, 5-fluorouracil,
gemcitabine, interferon-alpha, lomustine, and mitomycin C.
• a relatively late complication of allogeneic bone marrow
transplantation (BMT), usually presenting with AKI two to 12
months after transplantation. Total body irradiation and
graft-versus-host disease are the main factors associated
with thrombotic microangiopathy in these patients.
• Keys to management include gentle volume repletion and a
consideration of plasma exchange (controversial).
 AKI in BMT Recipients
• Sinusoidal obstruction syndrome (S.O.S, or veno-occlusive
disease of the liver) is characterized by blockage of the small
veins of the liver. Patients present with AKI and sodium
avidity (low urine output and low urine sodium), weight gain
with ascites and edema, painful hepatomegaly, and right
upper quadrant pain, and hyperbilirubinemia (bilirubin
greater than 2 mg/dL).

• Hepatic Doppler ultrasound is typically used to confirm or

suggest the diagnosis, with increased phasicity of portal
veins and the eventual development of portal flow reversal
the most common findings.
• AKI : mortality rate as high as 85% in patients requiring
renal replacement therapy.
• Several viruses have been implicated in acute
kidney injury in the setting of bone marrow
transplantation.
• These viruses include adenovirus, human
polyomavirus (BK virus or JC virus), and simian
polyomavirus.
 Nephrotoxic Chemotherapeutic Agents

• cisplatin and high-dose methotrexate,

mithramycin, and streptozocin - very potent
nephro-toxins and can have an acute effect.
• The nitrosoureas - lomustine and semustine -
more chronic progressive form of
tubulointerstitial injury that may not appear for
months to years.
• Gemcitabine can lead to thrombotic
microangiopathy that may take several months
to clinically manifest.
• Risk factors for nephrotoxicity : preexisting
chronic kidney disease, concomitant use of
other nephrotoxic agents, dehydration, and
intrinsic kidney disease secondary to cancer.

• Both physiological and pathological effects on

kidneys : cisplatin - acute vasoconstriction of
the renal vessels as well as direct tubular
damage.
 CHRONIC KIDNEY DISEASE
• IRMA Study -- 4684 patients
- chemo dose adjustment d/t CKD
•
CKD in BMT patients
 Paraprotein disease : Amyloidosis

Waxy appearance of intradermal amyloid deposition

Macroglossia showing teeth around the eye
indentations
 Primary Systemic Amyloidosis
Disease name Type of amyloid Precursor

M.Myeloma AL Light chains

Primary AL Light chains

Secondary Systemic Amyloidosis

Disease name Type of amyloid Precursor

Chronic inflammatory AA SAA

disease
Hemodialysis associate Aβ2- micro globulin β2- micro globulin
 Diagnosis of Amyloidosis

• -Can be very difficult

• -No blood test can diagnose or exclude amyloidosis

• -Usually relies on clinical suspicion

• -Possibility supported by
• Underlying chronic inflammatory state – AA
• Underlying plasma cell dyscrasia – AL
• Family history - hereditary
• Evidence of renal dysfunction
 A proposed histopathologic classification

- Renal amyloidosis was divided into 6 classes

- Similar to the classification of SLE

Sen S. Arch Pathol Lab Med 2010: 134: 532

 Treatment
• limited and research is still in progress.
• Differs depending on subtype.
• AL and AH
-High dose mephalan plus dexamethasone/prednisone
-In selected candidates autologous stem cell transplant
is an option.
- The goal with treatment is to get rid of clonal plasma
cells that lead to immunoglobulin protein
• AA: Treat the infection or chronic inflammatory
condition causing apo serum A protein elevation.
• Familial Mediterranean fever: Colchicine
• Other conditions are treated conservatively or
require organ transplant
• Prognosis is poor with this medical disorder.
Direct infiltration of the kidneys
End.