ANNA Meeting, Nov 2013

Kenar D. Jhaveri, M.DHofstra North Shore LIJ School of

Medicine, NYkjhaveri@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.There is a 5% increase in the risk of malignancy in patients with ESRDB.The commonest form of cancer found in patients with ESRD is lung cancerC.The risk of bladder cancer rises with increased time on dialysisD.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!

Patient Specific Factors Kidney Specific Factors Drug Specific Factors

Kidney Pathology 101

GlomeruliTubulesInterstitiumVasculature

Agents known to be nephrotoxic

CisplatinumMethotrexateGemcitabineCalcineurin InhibitorsBisphosphanatesTyrosine 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.Berman E., et al. N Engl J Med 2006;354:2006-13.Schrag D., et al. JNCI, Vol. 97, No. 16, August 17, 2005Schrag 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 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.

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 ◦ 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

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

MIDD

AL amyloidosis

Solomon et al NEJM 1991

Cast nephropathy

MIDD

AL amyloidosis

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.

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.

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When Ailments Pile Up, Asking Patients to Rethink Free Dialysis

By GINA KOLATA Published: March 31, 2011

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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.”

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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)

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• Unacceptable quality of life (failure to thrive)

• Acute complication• Dementia• Stroke•Cancer• Other

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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.

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Type of careDialysis 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%

Oncology Nephrology

Pharmacy

ONCO

Nephrology