ANNA Meeting, Nov 2013
Kenar D. Jhaveri, M.D
Hofstra North Shore LIJ School of
Medicine, NY
kjhaveri@nshs.edu

The field of nephrology that is deals with complications
of a cancer.











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

Which ONE of the following statements is correct regarding
the risk of malignancy in patients with ESRD?
A.
B.
C.
D.
There is a 5% increase in the risk of malignancy in
patients with ESRD
The commonest form of cancer found in patients with
ESRD is lung cancer
The risk of bladder cancer rises with increased time on
dialysis
The risk for kidney cancer rises with increased time on
dialysis.
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.



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.


Know that CKD and ESRD patients are at higher risk of
cancer than general population.
Screening? – would you advocate?

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?
Flombaum Cancer and the kidney,chap 6




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


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



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%
 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


CHEMOTHERAPY may be nephrotoxic
Many newer agents have many renal side effects and be
vigilant as you see some of these patients!
Intrinsic
Renal
Post
Renal
Pre Renal



Patient Specific Factors
Kidney Specific Factors
Drug Specific Factors
Kidney Pathology 101
Glomeruli
Tubules
Interstitium
Vasculature
Agents known to be nephrotoxic
Cisplatinum
Methotrexate
Gemcitabine
Calcineurin Inhibitors
Bisphosphanates
Tyrosine Kinase Inhibitors
Anti VEGF agents




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?


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







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





Hyponatremia, hypernatremia
Hypercalcemia
Hypomagnesemia
Hypokalemia and hyperkalemia
All have been discovered and be vigilant of that as
well.

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 pathophysiology of the pathology found on kidney biopsy?
A. Nephrin injury
 B. Endothelial damage
 C. Mesangial cell injury
 D. Fibril formation causing
glomerular damage.




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.

Prevalence

Renal Manifestations

Presentation

Treatment

Outcome on dialysis is poor
◦ MGUS 3.2% in people over 50
◦ Myeloma 13% of all hematologic cancers
◦ In a minority of patients paraprotein are pathogenic
◦ 3% of native kidney biopsies diagnose a paraprotein related disease
◦ Proteinuria and/or renal failure
◦ Reducing the supply of paraprotein
◦ Supporting or replacing compromised organ function
◦ Compared with other disease groups, 2-year survival is about 30% less.
◦ Response to chemotherapy equal but difficult to administer

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



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.
Cast
nephropathy
Cast
nephropathy
MIDD
MIDD
AL amyloidosis
AL amyloidosis
Solomon et al NEJM 1991

Clinical scenario

Clinical features cannot
distinguish among the
various patterns of renal
disease associated with
dysproteinemias.
Renal biopsy is necessary to
establish the individual
diagnosis.

◦ Known paraprotein with renal
dysfunction/proteinuria
◦ Renal dysfunction/proteinuria
and anemia
◦ Dipstick negative with high p/c
ratio

Treat the acute situation
◦ Optimize hemodynamics and intravascular volume
◦ Treat hypercalcemia aggressively
 IV saline
 Bisphosphonates
◦ Avoid nephrotoxins

Decrease the production of paraproteins
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

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.

41



When Ailments Pile Up, Asking Patients to Rethink Free
Dialysis
By GINA KOLATA
Published: March 31, 2011
42
 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
“Most patients with ESRD, especially those who are
not candidates for renal transplantation, have a
significantly shortened life expectancy.”
44
 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 (010) (1995)
45
• Unacceptable
quality of life (failure to
thrive)
• Acute complication
• Dementia
• Stroke
• Cancer
• Other
46




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

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”?



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


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.
50
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%
51
Pharmacy
ONCO
Nephrology
Oncology
Nephrology