Onconephrology shield the kidney while fighting cancer , dr ayman seddik

1. Dr Ayman Seddik ,M.Sc , MD
Ass.Prof. Nephrologist Ain Shams University
Nephrology Consultant

3. Outline
 What Is Onconephrology
 Scope Of Kidney Diseases In Cancer Patient
1. AKI In Cancer Patient
2. Cancer Associated Glomerulopathy
3. CHEMOTHERAPY Associated TIN
4. Hypercalcemia Of Malignancy
5. Tumour Lysis Syndrome

4. “Onco- Nephrology”
 The field of nephrology that is deals with complications of
a cancer.

10. Why is the Nephrologist called?
 Kidney disease either pre existing or developing in the course of
the cancer
 New Glomerular paraneoplastic disease
 Obstructive Nephropathy
 Tubular interstitial Damage
 Thrombotic microangiopathy
 Radiation Nephropathy
 Tumor invasion of the kidney
 Tumor lysis syndrome
 Multiple Myeloma
 Fluid and electrolyte disorders
 Decision regarding renal replacement therapy

12. GLOMERULAR DISEASES WITH
MALIGNANCY

13. Management of newly diagnosed membranous nephropathy.
Jean-François Cambier, and Pierre Ronco CJASN
2012;7:1701-1712
©2012 by American Society of Nephrology

15. Malignancy-induced minimal-change disease: the case of Hodgkin lymphoma.
Jean-François Cambier, and Pierre Ronco CJASN
2012;7:1701-1712
©2012 by American Society of Nephrology

20. Question 1
 Which ONE of the following statements is correct regarding
the risk of malignancy in patients with ESRD?

21. A. There is a 5% increase in the risk of malignancy in
patients with ESRD
B. The commonest form of cancer found in patients with
ESRD is lung cancer
C. The risk of bladder cancer rises with increased time on
dialysis
D. The risk for kidney cancer rises with increased time on
dialysis.

22. 1. The overall risk of cancer is increased in patients with ESRD, and the
distribution of tumor types resembles the pattern seen after transplantation.
2. The overall risk for cancer in this population of ESRD patients is approximately 20%.
3. Renal parenchymal cancers are increased in all categories of primary renal
disease, and the risk rises with time on dialysis treatment.
4. Cancers of the lung, colorectum, prostate, breast,
and stomach were not consistently increased in patients on dialysis.

23. GFR reduction and cancer risk? During a median follow up around 13 years, 370
cancer deaths were observed in study cohort.
 For every 10-mL/min/1.73m2 reduction in eGFR,
there was an increase in cancer-specific mortality of
18% in the fully adjusted model.
 This excess cancer mortality varied with site, with the
greatest risk for breast and urinary tract cancer
deaths
Iff S et al. Reduced estimated GFR and cancer mortality. AJKD 2013 in press.

24. As a Nurse? Know that CKD and ESRD patients are at higher risk of
cancer than general population.
 Screening? – would you advocate?

25. QUESTION 2 A 68 Y old Female with Laryngeal cancer received
chemotherapy with cisplatin. Five days later, CRT is
5.0, Na is 132, and mg is 0.3. Urine Na is high
 Cisplatin is stopped and renal function normalizes.
 What orders will the nephrologists give you to help
prevent this injury next time this patients gets
cisplatin?

26. Flombaum Cancer and the kidney,chap 6

28. QUESTION 3
 Ms Jem Sitaben is a 70 y.o. female with Pancreatic cancer
treated with DRUG Z ( cumulative dose 21,750 mg/m2)
referred to Renal service for poorly controlled HTN. BP 150/80
treated with Amlodipine, Atenolol and Furosemide.
CBC and crt normal at that time
 repeat renal consultation-ARF
 Hgb 9.7; Plt 49; Creat 1.9; LDH 553; Haptoglobin <6; U Prot
300+
 Creat remained stable at 2.0, offending agent was stopped.
Patient died from pancreatic disease progression

29. TMA- TTP/HUS syndrome
 Mitomycin C is associated with Hemolytic Uremic
Syndrome (HUS) at total cumulative doses above 40-60
mg/m2
 HUS usually occurs within 4-8 weeks after the last dose
and carries a poor prognosis

31. Gemcitabine
 Gemcitabine is a nucleoside analog with antineoplastic
activity against a variety of solid tumors including
pancreatic, non-small cell lung, bladder, ovarian and
breast carcinomas
 Mild proteinuria and microscopic hematuria may occur in
up to 50% of pt treat with Gemcitabine
 HUS is a well-described complication with an incidence of
0.31%-0.4%

32. Gemcitabine Hemolytic Uremic Syndrome
 The presentation is subacute with insidious onset of renal
dysfunction, hemolytic anemia, new or worsening
hypertension and thrombocytopenia
 Unrecognized, progression to fulminant acute renal
failure and hypertensive crisis can occur
 Useful Lab data: LDH, Haptoglobin, Smear Review,
Reticulocyte Count, Creat, Urinalysis

34. What do I need to know? CHEMOTHERAPY may be nephrotoxic
 Many newer agents have many renal side effects and be
vigilant as you see some of these patients!

35. Potential compartments of drug
induced injury
Pre Renal
Post
Renal
Intrinsic
Renal

36. Why is the Kidney Vulnerable to
Chemotherapy?
 Patient Specific Factors
 Kidney Specific Factors
 Drug Specific Factors

37. Kidney Pathology 101
Glomeruli
Tubules
Interstitium
Vasculature

39. 1-Renal vasculature

40. 2- Glomeruli

41. 3- acute tubular necrosis

42. 4- Tubulointerstitial nephritis

48. Outline
Agents known to be nephrotoxic
Cisplatinum
Methotrexate
Gemcitabine
Calcineurin Inhibitors
Bisphosphanates
Tyrosine Kinase Inhibitors
Anti VEGF agents

49. Watch out kidney, chemo is here!

50. TUMOUR LYSIS SYNDROME

51. Definition
 Potentially fatal metabolic complication that occurs in
some patients with cancer
 Can result in potentially life threatening metabolic
and electrolyte abnormalities

52. Pathophysiology
 Involves a complex series of events related to the
liberation of intracellular contents from tumor cells
and inability of the kidneys to excrete and maintain
normal serum composition

53. Manifestations
 Usually occurs within 24-48 hours after initiation of
chemotherapy and may persist for 5-7 days post
therapy
 May occur as early as 6 hours post chemotherapy
administration

55. Tumor Types
 Non-Hodgkins lymphoma
 Burkitt’s
 High grade T-cell
 Acute Leukemia’s
 Acute Promyelocytic leukemia
 Acute lymphoblastic leukemia
 Chronic Lymphoblastic leukemia
 Solid tumors
 Small cell lung cancer
 Breast cancer

57. Prevention
 Identify patients at risk
 Monitor for all electrolyte abnormalities
 Administer allopurinol,
 Decrease uric acid levels by interfering with purine
metabolism through the inhibition of the enzyme xanthine
oxidase that is essential for the conversion of nucleic acids to
uric acid
 Alkalinization of the urine
 Prevent as much as possible renal damage
 Sodium bicarbonate solution
 Decreases the risk of renal obstruction, however urinary
alkalinization should be used cautiously because of risk of
precipitation in the kidneys of calcium-phosphorous binding
and the risk of hypocalcemic induced neuromuscular
irritability

58. Prevention
 Rasburicase- recombinant urate oxidase-
 Reduces the uric acid pool
 Reduces existing uric acid
 Prevents the accumulation of xanthines and
hypoxanthine
 Does not require alkalinization
 Facilitates phosphorous excretion
 Dosing:
 IV over 30 minutes
 0.2 mg/kg IV QD or BID

59. Management
 Hydration
 3 Liters daily
 Aggressive hydration starting 1-2 days prior to
chemotherapy and continuing for a few days post
chemotherapy

60. Management
 Diuretics:
 Furosemide
 Renal dose Dopamine- 2-4 mcg/kg
 Prevents:
 Fluid overload
 Electrolyte imbalance
 Complications of uric acid buildup

61. Management
 Hyperkalemia
 Kayexalate with sorbitol
 PO
 Rectal
 Calcium Gluconate
 Sodium bicarbonate
 Hypertonic dextrose and regular insulin
 Albuterol (Ventolin) or another beta stimulant

62. Management
 Dialysis: Hemodialysis/CVVH/CRRT( Requires
ICU Care)
 Used for patients unresponsive to preventive
measures and electrolyte corrections
 Used to remove uric acid
 Used in patients with:
 Serum potassium >6 mEq/L
 Uric acid >10 mg/dl
 Phosphorous > 10 mg/dl
 Symptomatic hypocalcemia
 Presence of volume overload

63. Medication Management
 Avoid nephrotoxic medications
 Avoid agents which block tubular reabsorption of uric
acid
 Aspirin
 Probencid
 Thiazide diuretics
 Radiographic contrast containing iodine

64. Nursing Interventions
 Symptom management
 Maintenance of fluid status
 Review of systems
 Cardiac via EKG
 Neurologic
 Neuromuscular
 Gastrointestinal
 Renal

65. Nursing Interventions
 Monitor weights at least daily
 Daily EKG’s
 Monitor for altered level of consciousness
 Strict I&O
 Check pH of urine with each void, goal is to keep
pH >7.0
 Monitor for signs and symptoms of nausea and
vomiting, administer antiemetics as ordered

66. CASE 4 Mr. Tumor has lung cancer( NSCLC). His serum calcium is 14.
 The patient is in acute renal failure as well. The Nephrologist initiated
dialysis for the hypercalcemia induced AKI
 What is causing the high calcium?
 How can you medical treat that? Before dialysis?

68. TTT MALIGNANCY INDUCED
HYPERCALCEMIA

69. ELECTROLYTE ABNORMALITIES
 Imatinib (mTKI) induces hypophosphatemia
 inhibition of platelet-derived growth factor receptor expressed on
osteoclasts
 subsequent decreased bone resorption
 decreased calcium, and phosphate egress from the bone
 PTH levels (due to decreased calcium egress) and further renal
phosphate wasting
 Cetuximab/Panitumumab-EGFR antibody
 Hypomagnesemia-due to renal wasting
 Possible inhibition of TRPM6 cation channel
Berman E., et al. N Engl J Med 2006;354:2006-13.
Schrag D., et al. JNCI, Vol. 97, No. 16, August 17, 2005

71. CETUXIMAB
 Hypomagnesemia incidence of 1.8-5.8% in initial trials
 Higher incidence when measured more rigorously
 Duration of therapy, age and baseline Mg
 IV repletion required
 Calcium and Potassium repletion also required
 Improves/resolves appox 4-6 weeks after stopping agent
 ? Role of Amiloride
Fakih et al, Clin C Can 2006.
Vij R, Sachdeva M. NKF 2010 Abstract

74. Cancers and electrolytes
 Hyponatremia, hypernatremia
 Hypercalcemia
 Hypomagnesemia
 Hypokalemia and hyperkalemia
 All have been discovered and be vigilant of that as well.

75. QUESTION 4 A 56 y old male with IgG kappa myeloma develops
proteinuria. A kidney biopsy reveals nodular sclerosis.
Congo red staining is negative. What is the patho-
physiology of the pathology found on kidney biopsy?
 A. Nephrin injury
 B. Endothelial damage
 C. Mesangial cell injury
 D. Fibril formation causing
glomerular damage.

76. Paraproteinemia and the Kidney

77. Dysproteinemia
 Abnormal, usually
excessive, synthesis of
immunoglobulin molecules
or subunits.
 Result from clonal
proliferations of plasma
cells or B lymphocytes.
 Majority of cases are
caused by plasma cell
proliferations rather than B-
cell lymphoproliferative
disorders.

78. Dysproteinemia
 Prevalence
◦ MGUS 3.2% in people over 50
◦ Myeloma 13% of all hematologic cancers
 Renal Manifestations
◦ In a minority of patients paraprotein are pathogenic
◦ 3% of native kidney biopsies diagnose a paraprotein related disease
 Presentation
◦ Proteinuria and/or renal failure
 Treatment
◦ Reducing the supply of paraprotein
◦ Supporting or replacing compromised organ function
 Outcome on dialysis is poor
◦ Compared with other disease groups, 2-year survival is about 30% less.
◦ Response to chemotherapy equal but difficult to administer

79. Paraprotein Induced Renal injury
 TUBULAR
 Cast nephropathy
 Light chain Fanconi syndrome
 GLOMERULAR
 Amyloidosis
 Monoclonal immunoglobulin deposition disease (MIDD)
 Immunotactoid and fibrillary glomerulonephritis
 Cryoglobulinemic glomerulonephritis
 Waldenstroms macroglobulinemic glomerulonephritis
 Proliferative glomerulonephritis and monoclonal
immunoglobulin deposits

80. Normal Light Chain Physiology
 Free light chains are freely
filtered.
 Reabsorbed and catabolized
by proximal tubular epithelial
cells.
 When the light chains in the
tubular filtrate exceed the
maximal reabsorptive capacity
of the proximal tubule.
◦ precipitate, producing light
chain cast nephropathy
(myeloma kidney)
◦ remain in the tubular filtrate
resulting in light chain
proteinuria.

81. Light chain proteins are the primary determinant
of the pattern of renal parenchymal deposition
and clinical disease
Cast
nephropathy
MIDD
AL amyloidosis
Solomon et al NEJM 1991
Cast
nephropathy
MIDD
AL amyloidosis

82. Clinical Approach
 Clinical scenario
◦ Known paraprotein with renal
dysfunction/proteinuria
◦ Renal dysfunction/proteinuria
and anemia
◦ Dipstick negative with high p/c
ratio
 Clinical features cannot
distinguish among the various
patterns of renal disease
associated with
dysproteinemias.
 Renal biopsy is necessary to
establish the individual
diagnosis.

83. Management of AKI from
Paraprotein-Mediated Disease
 Treat the acute situation
 Optimize hemodynamics and intravascular volume
 Treat hypercalcemia aggressively
 IV saline
 Bisphosphonates
 Avoid nephrotoxins
 Decrease the production of paraproteins

84. Light chain cast nephropathy (also known as myeloma kidney).
Heher E C et al. CJASN doi:10.2215/CJN.12231212
©2013 by American Society of Nephrology

85. Question 5
 A 89 year old male on HD for cardiac related renal disease
from heart failure now gets diagnosed with mets from
prostate cancer. He has been on dialysis for 2 years. He
reads a NY Times article on withdrawal of dialysis and cost
to the society and comes to his nephrologist and says, “ I
have lived my life- please withdraw me from dialysis”.
What does the nephrologist do?
 Call a psychiatry consult
 Arrange a family meeting with social worker as well
 Discuss the reasons why the patient want’s to come off
dialysis
 Arrange for end of life care services and agree with the
patient’s wishes.
85

86.  When Ailments Pile Up, Asking Patients to Rethink Free
Dialysis
 By GINA KOLATA
 Published: March 31, 2011
86

87. ESRD End-of-Life
Demographics
Rising median age of dialysis
population
48% > 65 yrs old
Over 72,000 dialysis patients die
per year
~20% die after decision to
withdraw
High percentage with
comorbidities
High in-hospital death (61% in
one study)
Unknown but low % die with
hospice

88. “Most patients with ESRD, especially those who are not
candidates for renal transplantation, have a significantly
shortened life expectancy.”
88

89. Frequency of Death in Dialysis Units
Average of 17 deaths per dialysis unit/yr
78% of units withdrew at least 1 patient
(1990)
Mean # withdrawn: 3 (0-20)
Most nephrologists withdraw at least one
patient/yr
Mean # withdrawn/nephrologist/yr: 3 (0-
10) (1995)
89

90. Reasons for Withdrawal
•Unacceptable quality of life (failure to
thrive)
•Acute complication
•Dementia
•Stroke
•Cancer
•Other
90

91. Barriers
 Lack of education, especially of nephrologists
 Unwillingness of dialysis corporations to respect dialysis
patients’ preference for DNR order
 Patient/family denial of permanent nature of ESRD
 Lack of patient awareness of life-limiting nature of ESRD
resulting in many not wanting to discuss end-of-life issues

92. Case 6
 A 45 year old with metastatic renal cancer is admitted to the intensive
care unit. The patient has failed all possible treatments for renal cancer
including tyrosine kinase inhibitors, IL-2 agents, and research protocols.
He is admitted for acute shortness of breath and quickly intubated for
ARDS. Two days into his course, he develops oliguric acute renal injury and
septic shock requiring three pressor support medications. A renal consult
is called to offer CVVHDF. Nephrology team #1 offers the therapy.
Nephrology team #2 is consulted for a second opinion. Nephrology team
#2 is consulted and a “surprise question” is asked and dialysis is not
offered to the patient.
 Which consult team is giving appropriate care?
 Which consult team is treating the family ?
 Which consult team is treating the “lawyers”?

93.  The Surprise Question: “Would I be surprised if
this patient dies in the next year?”
◦ Estimate of prognosis is based upon patient’s
age, functional status, medical condition,
including comorbidity and recent sentinel events,
and this “surprise” question
◦ Surprise question prognostic tool is available
online: http://touchcalc.com/calculators/sq
◦ There is not the same degree of precision of
tools to estimate prognosis for patients with AKI
Identifying Patients At Risk to Die in 6-12 Months

94.  Recommendation No. 7: Special Patient Groups
 It is reasonable to consider not initiating or withdrawing
dialysis for patients with ARF or ESRD who have a terminal
illness from a non-renal cause or whose medical condition
precludes the technical process of dialysis.
RPA
94

95. 95
Type of care Dialysis patients Cancer patients
Hospitalization 76.0% 61.3%
Average number of
days hospitalized
9.8 5.1
Intensive care unit 48.9% 24.0%
Average number of
days in ICU
3.5 1.3
Ventilator, feeding
tube or CPR
29.0% 9.0%
Hospice 20.0% 55.0%
In-hospital death 44.8% 29.0%

96. CHEMOTHERAPY-INDUCED RENAL
DAMAGE
 Nephrotoxicity is the major dose-limiting toxicity for
cisplatin
 Both acute and late-onset toxicities occur
 aggressive replacement of magnesium (lost when the
proximal tubule is damaged), saline hydration or
mannitol infusion
 High dose methotrexate : postrenal obstruction by
precipitating in the tubules of the nephron
 also direct toxicity

99. Oncology Nephrology
Pharmacy
ONCO
Nephrology