Review Article
A
From the Division of Nephrology, Univer- cute kidney injury is common in patients with cancer1,2; the
sity of Virginia Health System, Charlottes- incidence and severity vary, depending on the type and stage of cancer, the
ville (M.H.R.); and the Section of Nephrol-
ogy, Yale University School of Medicine, treatment regimen, and coexisting conditions.3 In a 7-year Danish study of
New Haven, and the Veterans Affairs 37,267 incident cases of cancer, the 1-year risk of acute kidney injury, as defined
Medical Center, West Haven both in by the risk, injury, failure, loss of kidney function, and end-stage kidney disease
Connecticut (M.A.P.). Address reprint re-
quests to Dr. Rosner at the Division of (RIFLE) classification (Table1), was 17.5%.4 The 5-year risk for the individual risk,
Nephrology, University of Virginia Health injury, and failure categories was 27.0%, 14.6%, and 7.6%, respectively. Further-
System, Box 800133, Charlottesville, VA more, 5.1% of patients in whom acute kidney injury developed required long-term
22908, or at mhr9r@virginia.edu.
dialysis within 1 year.4
N Engl J Med 2017;376:1770-81. Patients with cancer who are critically ill have the highest risk of acute kidney
DOI: 10.1056/NEJMra1613984
Copyright 2017 Massachusetts Medical Society. injury (incidence, 54%),5 particularly patients who have hematologic cancers or
multiple myeloma and those with septic shock.6 This review provides an overview
of acute kidney injury in patients with cancer.
Acute kidney injury in patients with cancer is associated with substantial morbid-
ity and mortality.3,11,12 In a study involving patients with hematologic cancers who
were undergoing induction therapy, the 8-week mortality was 13.6% among pa-
tients in the RIFLE risk category and was 61.7% among those in the failure cate-
gory who required dialysis, as compared with 3.8% among patients without any
evidence of acute kidney injury.11 In another study, among patients with cancer
who were in the intensive care unit, the mortality was 49.0% for those in the RIFLE
risk category, 62.3% for those in the injury category, and 86.8% for those in the
failure category, as compared with 13.6% for patients without acute kidney injury.5
However, increased mortality has not been reported in all studies, possibly owing
to differences among studies in the age, overall severity of illness, and functional
status of the patients.13
Acute kidney injury increases the risk of toxic effects from systemic chemo-
therapy, jeopardizes the continuation of cancer therapy, and limits patient partici-
pation in possibly life-saving clinical trials. Among Table 1. RIFLE (Risk, Injury, Failure, Loss of Kidney Function, and End-Stage
patients being treated with potentially curative Kidney Disease) Classification of Acute Kidney Injury.*
regimens, acute kidney injury may necessitate
dose reductions or use of alternative regimens Classification of Injury Change in Kidney Function
that have better renal safety records but marginal Risk Cr increased by 1.5 times or GFR decreased by >25%
efficacy.2,14 Injury Cr increased by 2 times or GFR decreased by >50%
Failure Cr increased by 3 times or GFR decreased by >75%,
or Cr >0.5 mg/dl (44 mol/liter) if baseline value
C a ncer s A sso ci ated w i th Acu te 4 mg/dl (350 mol/liter)
K idne y Inj ur y
Loss of kidney function Complete loss of kidney function for >4 wk
Hematologic Cancers Other Than Myeloma End-stage kidney disease Complete loss of kidney function for >3 mo
Acute kidney injury occurs in up to 60% of pa-
tients with hematologic cancers at some point in * Cr denotes serum creatinine, and GFR glomerular filtration rate.
the disease course,15,16 most commonly in asso-
ciation with sepsis, nephrotoxins, the tumor lysis
syndrome (especially with rapidly growing can- Table 2. Types of Acute Kidney Injury in Patients with Hematologic Cancers.*
cers such as Burkitts lymphoma), or volume de-
Cancer-related injury
pletion.16-18 Other, less common associations must
also be considered in the differential diagnosis Tumor infiltration of the kidneys
(Table2). Obstructive nephropathy related to retroperitoneal lymphadenopathy
The kidney is the most common extrareticu- Lysozymuria (CMML or AML) with direct tubular injury
lar site of leukemic and lymphomatous infiltra- Hemophagocytic lymphohistiocytosis with acute interstitial disease
tion, and tumor-cell infiltrates in the kidney are Vascular occlusion associated with DIC and hyperleukocytosis (rare)
seen in up to 30% of patients with lymphoma
Hypercalcemia with hemodynamic acute kidney injury and acute nephro
and up to 60% of patients on autopsy.19,20 How- calcinosis
ever, renal infiltration causes acute kidney injury Glomerular diseases (minimal change disease, focal segmental glomerulo-
in only 1% of patients with acute leukemia and in sclerosis, membranoproliferative glomerulonephritis, membranous
even fewer patients with lymphoma or chronic nephropathy, amyloidosis, immunotactoid glomerulonephritis, fibrillary
glomerulonephritis, crescentic glomerulonephritis)
leukemia.21,22 In patients with massive tumor-
cell infiltration, tubular compression and dis- Therapy-related injury
ruption of the microcirculation set the stage for Nephrotoxicity (including thrombotic microangiopathy, acute tubular injury,
tubulointerstitial nephritis, and glomerular disease)
acute kidney injury. Flank pain and hematuria,
along with hypertension, may accompany acute Tumor lysis syndrome with acute uric acid nephropathy (may occur spon
taneously)
kidney injury, although many patients are asymp-
tomatic. Renal imaging with ultrasonography or Intratubular obstruction from medications (e.g., methotrexate)
computed tomography generally shows bilaterally Other types of injuries
enlarged kidneys. A kidney biopsy is diagnostic, Volume depletion
revealing diffuse infiltration of the interstitium Sepsis and septic shock
with malignant cells that can be identified with Nephrotoxicity of radiocontrast agents
specific stains and immunologic markers. Prompt
Nephrotoxicity of common medications, such as NSAIDs, ACE inhibitors,
administration of chemotherapy may lead to ARBs, and antibiotics
rapid improvement in kidney function; the long-
term prognosis depends on the response to * ACE denotes angiotensin-converting enzyme, AML acute monocytic leukemia,
ARBs angiotensin-receptor blockers, CMML chronic myelomonocytic leuke-
therapy.21 mia, DIC disseminated intravascular coagulation, and NSAIDs nonsteroidal
antiinflammatory drugs.
Multiple Myeloma Reported associations with focal segmental glomerulosclerosis, membranous
nephropathy, and crescentic glomerulonephritis are rare.
Acute kidney injury complicates multiple myeloma
in, depending on the definition used, 20 to 50%
of patients.23-25 Nephrotoxic effects often develop kidney injury), light-chainrelated proximal tubu-
from overproduction of monoclonal immuno- lar injury, and various glomerulopathies such as
globulins and free light chains, leading to cast light-chain deposition disease and amyloid light-
nephropathy (the most common cause of acute chain (AL) amyloidosis. Furthermore, metabolic
Overproduction Tubular
manifestations
Kappa Heavy Proximal
or lambda or immunoglobulin convoluted tubule
light chains chains
Proximal
straight tubule Obstruction
Urine albumin Urine albumin (cast formation)
>2 g/day < Thin
2 g/day
descending limb Thick
ascending limb
Figure 1. Diagnostic Approach to Patients Presenting with Acute Kidney Injury and Suspected Myeloma.
In patients with multiple myeloma, various glomerular and tubular manifestations can develop. Either isolated light (kappa or lambda) or
heavy immunoglobulin chains can lead to injury. Patients with urine albumin levels higher than 2 g per day usually have one of a variety
of glomerular lesions, whereas patients with lower urine albumin levels usually have a proximal tubulopathy or cast nephropathy. The stains
are WrightGiemsa (multiple myeloma) and hematoxylin and eosin (cast nephropathy). AH denotes amyloid heavy chain, AL amyloid
light chain, FLC free light chain, GN glomerulonephritis, LC light chain, and THP TammHorsfall protein.
disturbances (e.g., hypercalcemia and hyperuri- other key mechanism of injury is proximal tubu-
cemia), sepsis, and nephrotoxin exposure may lar reabsorption of massive amounts of free light
lead to acute kidney injury and may exacerbate chains, leading to activation of inflammatory
paraprotein-related kidney injury. Factors associ- cytokines, oxidative stress, apoptosis, and ulti-
ated with acute kidney injury in patients with mately, fibrosis.27,28 Thus, a decrease in the glo-
myeloma are shown in Figure 1. merular filtration rate due to increased intra-
Cast nephropathy develops when large amounts luminal tubular pressure, together with local
of free light chains, which are filtered at the interstitial inflammation and acute tubular in-
glomerulus, bind to TammHorsfall protein jury, results in acute kidney injury.24
(uromodulin) in the tubules, forming insoluble The diagnosis of cast nephropathy is facili-
casts that cause intrarenal obstruction and sub- tated by measurement of serum free light chains
sequent tubulointerstitial inflammation.26 An- with the use of a nephelometric immunoassay
chloride cotransporter and leads to marked natri- geneic vs. autologous), and the chemotherapeu-
uresis and volume depletion; nausea, vomiting, and tic conditioning regimen (high-dose vs. reduced-
ileus with resultant volume depletion; calcium- intensity).70 Approximately 5% of hematopoietic
induced renal vasoconstriction with resultant stem-cell transplant recipients with severe acute
decreases in renal blood flow63,64; nephrogenic kidney injury require dialysis.71,72
diabetes insipidus; and acute nephrocalcinosis Common risk factors for and causes of acute
from severe hypercalcemia (and hyperphospha- kidney injury after transplantation include vol-
temia). ume depletion, sepsis, nephrotoxic medications,
Treatment of hypercalcemia-induced acute kid- graft-versus-host-disease (GVHD), and the sinu-
ney injury relies on restoration of intravascular soidal obstruction syndrome.73,74 GVHD, a compli-
volume and renal perfusion, an increase in the cation of hematopoietic stem-cell transplantation,
glomerular filtration rate, and rapid lowering of causes tissue and endothelial damage through
the serum calcium level, followed by a sustained T-cell and cytokine-mediated injury.73 Gastroin-
therapeutic phase focused on maintaining a testinal mucosal involvement by GVHD contrib-
normal serum calcium level. The first step in utes to prerenal acute kidney injury through
therapy is aggressive intravenous hydration with poor fluid intake and excessive gastrointestinal
0.9% normal saline (200 to 250 ml per hour). losses. The sinusoidal obstruction syndrome, an
Loop diuretics are of little benefit, since they independent risk factor for acute kidney injury,
increase excretion of renal calcium, which may clinically mimics the hepatorenal syndrome be-
precipitate in the kidney, and also confer a risk cause of the associated acute portal hypertension
of hypovolemia. Thus, diuretics should be used that develops from hepatic sinusoidal injury.70,73,74
only in patients with hypervolemia.65 Severe cases Patients with hematopoietic stem-cell transplants
of acute kidney injury, which are often charac- are often prescribed medications such as vanco-
terized by oligoanuria, may not be amenable to mycin, aminoglycosides, acyclovir, and ampho-
intravenous hydration, whereas hemodialysis with tericin, which can cause acute kidney injury
a low calcium dialysate effectively corrects hyper- through mechanisms such as direct nephrotox-
calcemia.66 After this initial therapeutic stage, icity and tubulointerstitial nephritis.70,73,74 Calci-
medications that diminish bone calcium release neurin inhibitors can also cause hemodynamic
(bisphosphonates, calcitonin, or both) are used acute kidney injury and have been associated
to maintain normocalcemia. If pamidronate is with the development of thrombotic microangi-
used for bisphosphonate therapy, the dose must opathy.70,73,74 In addition, viral infections in
be adjusted for kidney function; zoledronic acid particular, adenovirus, BK virus, and cytomega-
should be avoided. A newer therapeutic option lovirus infections are associated with acute
that does not require dosing modification is kidney injury (tubulointerstitial nephritis and
denosumab, a humanized monoclonal antibody glomerulonephritis).
that neutralizes the receptor activator of nuclear
factor- ligand and reduces osteoblast activity Chemo ther a py-Induced Acu te
and bone calcium release.67 Recent studies sup- K idne y Inj ur y
port the use of denosumab in patients with
cancer-associated hypercalcemia.68,69 Traditional chemotherapeutic agents, newer tar-
geted therapies, and evolving immunotherapies
are extending the lives of patients with malig-
Hem at op oie t ic S tem- Cel l
T r a nspl a n tat ion a nd Acu te nant disease. Unfortunately, acute kidney injury
K idne y Inj ur y remains an important and growing complica-
tion of drug therapy in patients with cancer.75,76
Hematopoietic stem-cell transplantation is fre- Table3 lists commonly used drugs, their mecha-
quently complicated by acute kidney injury.70 The nisms of action, associated renal histopatho-
published incidence of acute kidney injury asso- logical features, and resulting clinical nephro-
ciated with hematopoietic stem-cell transplanta- toxic effects.
tion is wide-ranging (10% to 73%), primarily A number of conventional chemotherapeutic
because of variations in the definition of acute agents cause acute kidney injury.75-77 These drugs
kidney injury, the type of transplant used (allo- may injure the renal microvasculature, glomeru-
1776
Medication Mechanism of Action Renal Histopathological Features Clinical Nephrotoxic Effects
Chemotherapeutic agents
Cisplatin Cross-linking and interference with DNA replication Acute tubular injury and acute Acute kidney injury, proximal tubulopathy,
tubular necrosis Fanconis syndrome, NDI, sodium and
magnesium wasting
Ifosfamide Nitrogen mustard alkylating agent; inhibition of DNA Acute tubular injury and acute Acute kidney injury, proximal tubulopathy,
synthesis through DNA strand-breaking effects tubular necrosis Fanconis syndrome, NDI
Pemetrexed Antifolate agent; inhibition of dihydrofolate reductase, Acute tubular injury and acute Acute kidney injury, proximal tubulopathy,
thymidylate synthase, and glycinamide ribonucleo- tubular necrosis Fanconis syndrome, NDI
tide formyltransferase
Methotrexate Antifolate agent; inhibition of dihydrofolate reductase Crystalline nephropathy and acute Acute kidney injury
tubular injury
Pamidronate Pyrophosphate analogue; associated with moderate Focal segmental glomerulosclerosis, Nephrotic syndrome, acute kidney injury
FPPS inhibition acute tubular injury
The
Zoledronic acid Pyrophosphate analogue; associated with potent FPPS Acute tubular injury and acute Acute kidney injury
inhibition tubular necrosis
Targeted agents
Anti-VEGF drugs VEGF-receptor antibody or soluble receptor; inhibition Thrombotic microangiopathy Acute kidney injury, proteinuria, hypertension
of VEGF signaling
Tyrosine kinase or multikinase inhibitors Inhibition of tyrosine kinase or multikinase signaling, Thrombotic microangiopathy, focal Acute kidney injury, proteinuria, hypertension
(sunitinib, sorafenib, pazopanib) with activity against RAF kinase and several receptor segmental glomerulosclerosis,
tyrosine kinases (e.g., VEGF, PDGF) tubulointerstitial nephritis
BRAF inhibitors (vemurafenib and Inhibition of the mutated BRAF V600E kinase that leads Acute tubular injury, tubulointersti- Acute kidney injury, electrolyte disorders
dabrafenib) to reduced signaling through the aberrant MAPK tial nephritis
pathway
n e w e ng l a n d j o u r na l
ALK inhibitors (crizotinib) Inhibition of the mutated anaplastic lymphoma kinase Acute tubular injury, tubulointersti- Acute kidney injury, electrolyte disorders, renal
glomerulonephritis
PD-1 inhibitors T-cell activation by antibody blocking PD-1 receptor Tubulointerstitial nephritis Acute kidney injury
Chimeric antigen receptor T cells T-cell targeting of specific tumor-cell antigens No pathological features described Capillary leak syndrome with prerenal acute
kidney injury
* CTLA-4 denotes cytotoxic T-lymphocyte antigen 4, FPPS farnesyl pyrophosphate synthase, MAPK mitogen-activated protein kinase, NDI nephrogenic diabetes insipidus, PD-1 programmed
death 1, PDGF platelet-derived growth factor, STAT signal transducer and activator of transcription, and VEGF vascular endothelial growth factor.
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Carboplatin and oxaliplatin are less nephrotoxic than cisplatin.
In some cases, tubulointerstitial nephritis is accompanied by granulomatous interstitial nephritis.
Acute Kidney Injury in Patients with Cancer
Mitomycin C
Gemcitabine
Pamidronate
Antiangiogenesis drugs Dysproteinemia-related
Interferon
Antiangiogenesis drugs Drug-induced
Metabolic
Proximal
convoluted
tubule
Afferent
arteriole
Efferent
arteriole
Glomerulus
Collecting
tubule
Distal
Acute tubular injury
convoluted
tubule
Tubulointerstitial injury
Platinums
Ifosfamide
Pemetrexed
Crizotinib Tyrosine kinase inhibitors
Zoledronic acid BRAF inhibitors
Loop of Henle
lus, tubular segments, and renal interstitium trolyte and acidbase disturbances), hyperten-
(Fig. 2). Clinical renal syndromes that develop sion, and chronic kidney disease.75 Thrombotic
with these drugs include acute kidney injury, microangiopathy, which has been reported in
proteinuriahematuria, the nephrotic syndrome, association with gemcitabine or mitomycin C
isolated tubulopathies (with accompanying elec- therapy, may cause endothelial injury in the renal
microvasculature.78,79 Focal and segmental glo- mechanism of kidney injury with BRAF inhibi-
merulosclerosis and minimal change disease, tors is unknown but may involve interference
along with acute tubular injury, complicate with the downstream mitogen-activated protein
pamidronate therapy by damaging the glomeru- kinase pathway, which increases renal suscepti-
lar (and tubular) epithelium, which promotes a bility to ischemic tubular injury. Drug discon-
form of drug-induced podocytopathy.75,77 Most tinuation is associated with reversal of acute
common is acute tubular injury or necrosis due kidney injury in approximately 80% of cases.80
to treatment with platinum-containing regimens, The anaplastic lymphoma kinase 1 inhibitor,
ifosfamide, zoledronic acid, pemetrexed, and nu- crizotinib, causes acute kidney injury through
merous other chemotherapeutic agents.75,76 These tubular injury and is associated with renal cyst
drugs can induce direct cellular toxicity as a re- formation, as well as electrolyte disturbances in
sult of their transport through tubular cells, in- rare cases.81,82
duction of mitochondrial injury, oxidative stress, Immunotherapy, such as treatment with inter-
and activation of apoptotic signaling pathways feron and high-dose interleukin-2, as well as
within cells.75,76 drugs that stimulate the hosts immune system
There are no well-established therapies to treat to destroy cancer cells, such as checkpoint in-
these forms of acute kidney injury, apart from hibitors and chimeric antigen receptor T cells,83-87
drug discontinuation and supportive measures. may also cause acute kidney injury. Interferon is
Other drug-induced forms of acute kidney injury associated with high-grade proteinuria, acute kid-
include obstructive and inflammatory interstitial ney injury, and evidence of glomerulopathies
injury resulting from intratubular crystal pre- minimal change disease and focal segmental
cipitation induced by methotrexate and intersti- glomerulosclerosis on kidney biopsy.84 Inter-
tial nephritis from various chemotherapeutic feron-related glomerular injury may be due to
agents, such as ifosfamide, carboplatin, and doxo- direct binding of interferon to podocyte receptors
rubicin.75,76 and alteration of normal cellular proliferation.87
Targeted agents, defined as drugs designed to Macrophage activation and skewing of the cyto-
target specific gene mutations in malignant tis- kine profile toward interleukin-6 and interleu-
sue, inhibit oncogenic signaling cascades associ- kin-13, which may affect permeability in podo-
ated with tumor growth. These agents, which are cytopathies, are also possible mechanisms.84
effective in the treatment of several cancers,78 Drug discontinuation (with or without glucocor-
have become a prominent cause of acute kidney ticoid therapy) is effective in reversing acute
injury. As with chemotherapeutic drugs, targeted kidney injury and proteinuria in patients who
agents cause injury in all nephron segments. have minimal change disease but is less effective
Acute kidney injury, low-grade and nephrotic in those with focal segmental glomerulosclerosis,
proteinuria, hypertension, and electrolyte distur- especially collapsing focal segmental glomerulo-
bances are observed with many of these drugs. sclerosis.84
Vascular injury and glomerular injury occur with The checkpoint inhibitors ipilimumab, nivolu
antiangiogenesis drugs targeting vascular endo- mab, and pembrolizumab activate host T cells
thelial growth factor.78,79 Although a number of to enhance tumor killing by preventing tumor
lesions have been described in association with ligand binding to cytotoxic T-lymphocyte anti-
these drugs, thrombotic microangiopathy (associ- gen 4 and programmed death 1 receptors, which
ated with agents targeting vascular endothelial deactivate T cells. However, this effect causes
growth factor) and focal segmental glomerulo- loss of self-tolerance (and perhaps tolerance of
sclerosis (associated with tyrosine kinase inhibi- other drugs), leading to various forms of autoim-
tors) are the most common and are frequently mune injury, including acute interstitial nephritis,
associated with acute kidney injury.79 which is associated with moderate-to-advanced-
Therapy with the BRAF (serinethreonine pro- stage acute kidney injury.85,86 Glucocorticoid ther-
tein kinase) inhibitors, vemurafenib and dabraf apy and drug discontinuation generally reverse
enib, is complicated by a dose-related acute acute kidney injury due to treatment with check-
kidney injury, which appears to be due to acute point inhibitors.85,86 Chimeric antigen receptor
tubulointerstitial injury, although the histologic T cells are engineered to express receptors that
data available in these cases are limited.80 The recognize and bind tumor antigens, ultimately
directly targeting and destroying cancer cells. life before the acute injury.89 Furthermore, the
Such therapy, however, may be complicated by patients preferences must be considered in the
the cytokine release syndrome, which can result decision regarding dialysis initiation. The pro-
in capillary leak and prerenal azotemia.87 cess of shared decision-making is recommended
for working through the issues regarding dialy-
sis initiation in these complex situations.90
T r e atmen t Decisions
for Pat ien t s w i th C a ncer
a nd Acu te K idne y Inj ur y Sum m a r y
Both the short-term and long-term outcomes of Acute kidney injury in patients with cancer has
acute kidney injury in patients with cancer are diverse causes and negative outcomes. Efforts to
poor, with one study showing a 60-day survival prevent acute kidney injury in this patient popu-
rate of only 14%.88 However, selected patients lation are likely to improve outcomes and allow
can benefit from aggressive care; thus, decisions patients to reap the benefits of advances in can-
regarding the initiation of dialysis are complex cer treatments.
and require input from the entire care team to No potential conflict of interest relevant to this article was
reported.
assess the reversibility of the acute injury, the Disclosure forms provided by the authors are available with
longer-term cancer prognosis, and the quality of the full text of this article at NEJM.org.
References
1. Janus N, Launay-Vacher V, Byloos E, injury in hematopoietic cell transplanta- ic leukemias (1958 to 1982). Cancer 1987;
et al. Cancer and renal insufficiency results tion. Semin Nephrol 2010;30:615-26. 60:827-37.
of the BIRMA study. Br J Cancer 2010;103: 10. Perazella MA. Renal vulnerability to 20. Lundberg WB, Cadman ED, Finch SC,
1815-21. drug toxicity. Clin J Am Soc Nephrol 2009; Capizzi RL. Renal failure secondary to
2. Canet E, Zafrani L, Lambert J, et al. 4:1275-83. leukemic infiltration of the kidneys. Am J
Acute kidney injury in patients with newly 11. Lahoti A, Kantarjian H, Salahudeen Med 1977;62:636-42.
diagnosed high-grade hematological ma- AK, et al. Predictors and outcome of acute 21. Lommatzsch SE, Bellizzi AM, Cathro
lignancies: impact on remission and sur- kidney injury in patients with acute my- HP, Rosner MH. Acute renal failure
vival. PLoS One 2013;8(2):e55870. elogenous leukemia or high-risk myelo- caused by renal infiltration by hemato-
3. Salahudeen AK, Doshi SM, Pawar T, dysplastic syndrome. Cancer 2010; 116: lymphoid malignancy. Ann Diagn Pathol
Nowshad G, Lahoti A, Shah P. Incidence 4063-8. 2006;10:230-4.
rate, clinical correlates, and outcomes of 12. Lam AQ, Humphreys BD. Onco- 22. Daas N, Polliack A, Cohen Y, et al.
AKI in patients admitted to a comprehen- nephrology: AKI in the cancer patient. Kidney involvement and renal manifesta-
sive cancer center. Clin J Am Soc Nephrol Clin J Am Soc Nephrol 2012;7:1692-700. tions in non-Hodgkins lymphoma and
2013;8:347-54. 13. Darmon M, Thiery G, Ciroldi M, et al. lymphocytic leukemia: a retrospective study
4. Christiansen CF, Johansen MB, Lange- Intensive care in patients with newly diag- in 700 patients. Eur J Haematol 2001;67:
berg WJ, Fryzek JP, Srensen HT. Inci- nosed malignancies and a need for cancer 158-64.
dence of acute kidney injury in cancer chemotherapy. Crit Care Med 2005; 33: 23. Eleutherakis-Papaiakovou V, Bamias A,
patients: a Danish population-based co- 2488-93. Gika D, et al. Renal failure in multiple my-
hort study. Eur J Intern Med 2011;22:399- 14. Cosmai L, Porta C, Gallieni M, Pera- eloma: incidence, correlations, and prog-
406. zella MA. Onco-nephrology: a decalogue. nostic significance. Leuk Lymphoma 2007;
5. Librio AB, Abreu KL, Silva GB Jr, et al. Nephrol Dial Transplant 2016;31:515-9. 48:337-41.
Predicting hospital mortality in critically 15. Khalil MA, Latif H, Rehman A, et al. 24. Hutchison CA, Batuman V, Behrens J,
ill cancer patients according to acute kid- Acute kidney injury in lymphoma: a single et al. The pathogenesis and diagnosis of
ney injury severity. Oncology 2011; 80: centre experience. Int J Nephrol 2014; acute kidney injury in multiple myeloma.
160-6. 2014:272961. Nat Rev Nephrol 2011;8:43-51.
6. Darmon M, Ciroldi M, Thiery G, 16. Darmon M, Vincent F, Canet E, et al. 25. Finkel KW, Cohen EP, Shirali A, Abu-
Schlemmer B, Azoulay E. Clinical review: Acute kidney injury in critically ill pa- dayyeh A. Paraprotein-related kidney dis-
specific aspects of acute renal failure in tients with haematological malignancies: ease: evaluation and treatment of myeloma
cancer patients. Crit Care 2006;10:211. results of a multicentre cohort study from cast nephropathy. Clin J Am Soc Nephrol
7. Rosolem MM, Rabello LS, Lisboa T, the Groupe de Recherche en Ranima- 2016;11:2273-9.
et al. Critically ill patients with cancer tion Respiratoire en Onco-Hmatologie. 26. Sanders PW, Booker BB. Pathobiology
and sepsis: clinical course and prognostic Nephrol Dial Transplant 2015;30:2006- of cast nephropathy from human Bence
factors. J Crit Care 2012;27:301-7. 13. Jones proteins. J Clin Invest 1992;89:630-9.
8. Benoit DD, Hoste EA, Depuydt PO, 17. Luciano RL, Brewster UC. Kidney in- 27. Basnayake K, Ying WZ, Wang PX,
et al. Outcome in critically ill medical pa- volvement in leukemia and lymphoma. Sanders PW. Immunoglobulin light chains
tients treated with renal replacement ther- Adv Chronic Kidney Dis 2014;21:27-35. activate tubular epithelial cells through
apy for acute renal failure: comparison 18. Benoit DD, Hoste EA. Acute kidney redox signaling. J Am Soc Nephrol 2010;
between patients with and those without injury in critically ill patients with cancer. 21:1165-73.
haematological malignancies. Nephrol Dial Crit Care Clin 2010;26:151-79. 28. Pote A, Zwizinski C, Simon EE, Me-
Transplant 2005;20:552-8. 19. Barcos M, Lane W, Gomez GA, et al. leg-Smith S, Batuman V. Cytotoxicity of
9. Kogon A, Hingorani S. Acute kidney An autopsy study of 1206 acute and chron- myeloma light chains in cultured human
kidney proximal tubule cells. Am J Kidney et al. Long-term outcome of patients Cairo MS. Guidelines for the management
Dis 2000;36:735-44. with multiple [corrected] myeloma-related of pediatric and adult tumor lysis syn-
29. Hutchison CA, Basnayake K, Cock- advanced renal failure following auto- drome: an evidence-based review. J Clin
well P. Serum free light chain assessment SCT. Bone Marrow Transplant 2013;48: Oncol 2008;26:2767-78.
in monoclonal gammopathy and kidney 1543-7. 56. Cortes J, Moore JO, Maziarz RT, et al.
disease. Nat Rev Nephrol 2009;5:621-8. 42. Burnette BL, Leung N, Rajkumar SV. Control of plasma uric acid in adults at
30. Dimopoulos MA, Sonneveld P, Leung Renal improvement in myeloma with bor risk for tumor lysis syndrome: efficacy and
N, et al. International Myeloma Working tezomib plus plasma exchange. N Engl J safety of rasburicase alone and rasburi-
Group recommendations for the diagno- Med 2011;364:2365-6. case followed by allopurinol compared
sis and management of myeloma-related 43. Hutchison CA, Cook M, Heyne N, et al. with allopurinol alone results of a mul-
renal impairment. J Clin Oncol 2016;34: European trial of free light chain removal ticenter phase III study. J Clin Oncol 2010;
1544-57. by extended haemodialysis in cast nephrop- 28:4207-13.
31. Nasr SH, Valeri AM, Sethi S, et al. athy (EuLITE): a randomised control trial. 57. Vadhan-Raj S, Fayad LE, Fanale MA,
Clinicopathologic correlations in multiple Trials 2008;9:55. et al. A randomized trial of a single-dose
myeloma: a case series of 190 patients with 44. Bridoux F, Fermand JP. Optimizing rasburicase versus five-daily doses in pa-
kidney biopsies. Am J Kidney Dis 2012;59: treatment strategies in myeloma cast ne- tients at risk for tumor lysis syndrome.
786-94. phropathy: rationale for a randomized Ann Oncol 2012;23:1640-5.
32. Ludwig H, Adam Z, Hajek R, et al. prospectivetrial. Adv Chronic Kidney Dis 58. Sherwood GB, Paschal RD, Adamski J.
Light chain-induced acute renal failure can 2012;19:333-41. Rasburicase-induced methemoglobinemia:
be reversed by bortezomib-doxorubicin- 45. Schmid M, Krishna N, Ravi P, et al. case report, literature review, and pro-
dexamethasone in multiple myeloma: re- Trends of acute kidney injury after radi- posed treatment algorithm. Clin Case Rep
sults of a phase II study. J Clin Oncol cal or partial nephrectomy for renal cell 2016;4:315-9.
2010;28:4635-41. carcinoma. Urol Oncol 2016;34(7):293.e1- 59. El-Husseini A, Sabucedo A, Lamarche J,
33. Hutchison CA, Cockwell P, Stringer S, 293.e10. Courville C, Peguero A. Acute kidney in-
et al. Early reduction of serum-free light 46. Schmid M, Abd-El-Barr AE, Gandaglia jury associated with tumor lysis syndrome:
chains associates with renal recovery in G, et al. Predictors of 30-day acute kidney a paradigm shift. Am J Emerg Med 2012;
myeloma kidney. J Am Soc Nephrol 2011; injury following radical and partial ne- 30(2):390.e3-390.e6.
22:1129-36. phrectomy for renal cell carcinoma. Urol 60. Rosner MH, Dalkin AC. Onco-nephrol-
34. Dimopoulos MA, Roussou M, Gkotza Oncol 2014;32:1259-66. ogy: the pathophysiology and treatment
manidou M, et al. The role of novel agents 47. Kim CS, Bae EH, Ma SK, Kweon SS, of malignancy-associated hypercalcemia.
on the reversibility of renal impairment in Kim SW. Impact of partial nephrectomy Clin J Am Soc Nephrol 2012;7:1722-9.
newly diagnosed symptomatic patients on kidney function in patients with renal 61. Mazzone PJ, Arroliga AC. Endocrine
with multiple myeloma. Leukemia 2013; cell carcinoma. BMC Nephrol 2014;15:181. paraneoplastic syndromes in lung cancer.
27:423-9. 48. Kim SP, Thompson RH, Boorjian SA, Curr Opin Pulm Med 2003;9:313-20.
35. Reule S, Sexton DJ, Solid CA, Chen SC, et al. Comparative effectiveness for sur- 62. Donovan PJ, Achong N, Griffin K,
Foley RN. ESRD due to multiple myeloma vival and renal function of partial and Galligan J, Pretorius CJ, McLeod DS.
in the United States, 2001-2010. J Am Soc radical nephrectomy for localized renal PTHrP-mediated hypercalcemia: causes and
Nephrol 2016;27:1487-94. tumors: a systematic review and meta- survival in 138 patients. J Clin Endocrinol
36. Chanan-Khan AA, Kaufman JL, Mehta analysis. J Urol 2012;188:51-7. Metab 2015;100:2024-9.
J, et al. Activity and safety of bortezomib 49. Smith ZL. Current status of minimally 63. Toka HR, Al-Romaih K, Koshy JM,
in multiple myeloma patients with advanced invasive surgery for renal cell carcinoma. et al. Deficiency of the calcium-sensing
renal failure: a multicenter retrospective Curr Urol Rep 2016;17:43. receptor in the kidney causes parathyroid
study. Blood 2007;109:2604-6. 50. Mirrakhimov AE, Voore P, Khan M, Ali hormone-independent hypocalciuria. J Am
37. Scheid C, Sonneveld P, Schmidt-Wolf AM. Tumor lysis syndrome: a clinical re- Soc Nephrol 2012;23:1879-90.
IG, et al. Bortezomib before and after view. World J Crit Care Med 2015;4:130-8. 64. Pargger H, Kaufmann MA, Drop LJ.
autologous stem cell transplantation over- 51. Cairo MS, Coiffier B, Reiter A, Younes Renal vascular hyperresponsiveness to ele-
comes the negative prognostic impact of A. Recommendations for the evaluation vated ionized calcium in spontaneously
renal impairment in newly diagnosed mul- of risk and prophylaxis of tumour lysis hypertensive rat kidneys. Intensive Care
tiple myeloma: a subgroup analysis from syndrome (TLS) in adults and children Med 1998;24:61-70.
the HOVON-65/GMMG-HD4 trial. Haema- with malignant diseases: an expert TLS 65. LeGrand SB, Leskuski D, Zama I. Nar-
tologica 2014;99:148-54. panel consensus. Br J Haematol 2010;149: rative review: furosemide for hypercalce-
38. Dimopoulos MA, Roussou M, Gav 578-86. mia: an unproven yet common practice.
riatopoulou M, et al. Bortezomib-based 52. Wilson FP, Berns JS. Tumor lysis syn- Ann Intern Med 2008;149:259-63.
triplets are associated with a high proba- drome: new challenges and recent ad- 66. Cardella CJ, Birkin BL, Rapoport A.
bility of dialysis independence and rapid vances. Adv Chronic Kidney Dis 2014;21: Role of dialysis in the treatment of severe
renal recovery in newly diagnosed myelo- 18-26. hypercalcemia: report of two cases suc-
ma patients with severe renal failure or 53. Shimada M, Johnson RJ, May WS Jr, cessfully treated with hemodialysis and
those requiring dialysis. Am J Hematol et al. A novel role for uric acid in acute kid- review of the literature. Clin Nephrol
2016;91:499-502. ney injury associated with tumour lysis 1979;12:285-90.
39. Hoy SM. Carfilzomib triple combina- syndrome. Nephrol Dial Transplant 2009; 67. Eastell R, Christiansen C, Grauer A,
tion therapy: a review in relapsed multiple 24:2960-4. et al. Effects of denosumab on bone turn-
myeloma. Target Oncol 2016;11:255-62. 54. Boles JM, Dutel JL, Briere J, et al. over markers in postmenopausal osteopo-
40. Neri P, Bahlis NJ, Paba-Prada C, Rich- Acute renal failure caused by extreme hy- rosis. J Bone Miner Res 2011;26:530-7.
ardson P. Treatment of relapsed/refractory perphosphatemia after chemotherapy of 68. Dietzek A, Connelly K, Cotugno M,
multiple myeloma. Cancer Treat Res 2016; an acute lymphoblastic leukemia. Cancer Bartel S, McDonnell AM. Denosumab in
169:169-94. 1984;53:2425-9. hypercalcemia of malignancy: a case series.
41. Glavey SV, Gertz MA, Dispenzieri A, 55. Coiffier B, Altman A, Pui CH, Younes A, J Oncol Pharm Pract 2015;21:143-7.
69. Adhikaree J, Newby Y, Sundar S. RE: estimated problem? Acta Clin Belg 2011; lapsing focal segmental glomerulosclero-
Denosumab for patients with persistent 66:337-45. sis. Clin J Am Soc Nephrol 2010;5:607-15.
or relapsed hypercalcemia of malignancy 77. Markowitz GS, Bomback AS, Perazella 85. Cortazar FB, Marrone KA, Troxell ML,
despite recent bisphosphonate treatment. MA. Drug-induced glomerular disease: di- et al. Clinicopathological features of acute
J Natl Cancer Inst 2015;107:509. rect cellular injury. Clin J Am Soc Nephrol kidney injury associated with immune
70. Hingorani S. Renal complications of 2015;10:1291-9. checkpoint inhibitors. Kidney Int 2016;
hematopoietic-cell transplantation. N Engl 78. Porta C, Cosmai L, Gallieni M, Pedraz 90:638-47.
J Med 2016;374:2256-67. zoli P, Malberti F. Renal effects of target- 86. Shirali AC, Perazella MA, Gettinger S.
71. Parikh CR, Yarlagadda SG, Storer B, ed anticancer therapies. Nat Rev Nephrol Association of acute interstitial nephritis
Sorror M, Storb R, Sandmaier B. Impact 2015;11:354-70. with programmed cell death 1 inhibitor
of acute kidney injury on long-term mor- 79. Izzedine H, Escudier B, Lhomme C, therapy in lung cancer patients. Am J Kid-
tality after nonmyeloablative hematopoi- et al. Kidney diseases associated with anti- ney Dis 2016;68:287-91.
etic cell transplantation. Biol Blood Mar- vascular endothelial growth factor (VEGF): 87. Xu XJ, Zhao HZ, Tang YM. Efficacy
row Transplant 2008;14:309-15. an 8-year observational study at a single and safety of adoptive immunotherapy us-
72. Ando M, Mori J, Ohashi K, et al. A com- center. Medicine (Baltimore) 2014;93:333-9. ing anti-CD19 chimeric antigen receptor
parative assessment of the RIFLE, AKIN 80. Wanchoo R, Jhaveri KD, Deray G, transduced T-cells: a systematic review of
and conventional criteria for acute Launay-Vacher V. Renal effects of BRAF phase I clinical trials. Leuk Lymphoma
k idney injury after hematopoietic SCT. inhibitors: a systematic review by the 2013;54:255-60.
Bone Marrow Transplant 2010;45:1427- Cancer and the Kidney International Net- 88. Lahoti A, Nates JL, Wakefield CD,
34. work. Clin Kidney J 2016;9:245-51. Price KJ, Salahudeen AK. Costs and out-
73. Parikh CR, Coca SG. Acute renal fail- 81. Izzedine H, El-Fekih RK, Perazella MA. comes of acute kidney injury in critically
ure in hematopoietic cell transplantation. The renal effects of ALK inhibitors. Invest ill patients with cancer. J Support Oncol
Kidney Int 2006;69:430-5. New Drugs 2016;34:643-9. 2011;9:149-55.
74. Keating GM. Defibrotide: a review of 82. Perazella MA, Izzedine H. New drug 89. Darmon M, Thiery G, Ciroldi M,
its use in severe hepatic veno-occlusive toxicities in the onco-nephrology world. Porcher R, Schlemmer B, Azoulay E.
disease following haematopoietic stem cell Kidney Int 2015;87:909-17. Should dialysis be offered to cancer pa-
transplantation. Clin Drug Investig 2014; 83. Ponce P, Cruz J, Travassos J, et al. Re- tients with acute kidney injury? Intensive
34:895-904. nal toxicity mediated by continuous infu- Care Med 2007;33:765-72.
75. Perazella MA. Onco-nephrology: renal sion of recombinant interleukin-2. Nephron 90. Shared decision-making in the appro-
toxicities of chemotherapeutic agents. Clin 1993;64:114-8. priate initiation of and withdrawal from
J Am Soc Nephrol 2012;7:1713-21. 84. Markowitz GS, Nasr SH, Stokes MB, dialysis. 2nd ed. Rockville, MD:Renal
76. Lameire N, Kruse V, Rottey S. Neph- DAgati VD. Treatment with IFN-alpha, Physicians Association, 2010.
rotoxicity of anticancer drugs an under- -beta, or -gamma is associated with col- Copyright 2017 Massachusetts Medical Society.