Onconephrology (from the Ancient Greek onkos (ὄγκος) meaning bulk, mass, or
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, nephros (νεφρός) meaning
kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
, and the suffix -logy (-λογία), meaning "study of") is a specialty in
nephrology
Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function (ren ...
that deals with the study of
kidney diseases
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...
in cancer patients. A
nephrologist
Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function (ren ...
who takes care of patients with cancer and kidney disease is called an onconephrologist. This branch of nephrology encompasses nephrotoxicity associated with existing and novel chemotherapeutics, kidney disease as it pertains to stem cell transplant, paraneoplastic kidney disorders, paraproteinemias (Myeloma and Amyloidosis), electrolyte disorders associated with cancer, and more as discussed below.
Scope of practice
As onconephrologists are primarily taking care of kidney disease in cancer patients, there are several aspects that are unique to this practice when compared to general nephrology. For example, patients receiving chemotherapy can experience
kidney injury from destruction of cancer cells. There are also various complex electrolyte disorders that can occur due to the cancer itself or are side effects of chemotherapeutics. One example, The Syndrome of Inappropriate Antidiuretic Hormone (
SIADH
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH ca ...
), a disorder of low
serum sodium
Sodium ions (Na) are necessary in small amounts for some types of plants,
but sodium as a nutrient is more generally needed in larger amounts by animals, due to their use of it for generation of nerve impulses and for maintenance of electrolyte ...
concentration, was first described in
lung cancer
Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
and is a common electrolyte disturbance seen in this population. Fluid, electrolytes and acid base disturbances are much more common and often severe in those who receive chemotherapy. Several
chemotherapeutic agents
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...
– for example
cisplatin
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, br ...
– are associated with acute and chronic kidney injuries.
Additionally, there is Increased recognition that primary hematological and oncological disorders can have an impact on the kidneys in the form of glomerular disease that can present with proteinuria, hematuria, hypertension, and kidney function decline. Examples include, hematological cancers like Monoclonal Gammopathies (
paraproteinemias
Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, espe ...
), which can have significant kidney implications in the form of
Cast Nephropathy
Myeloma cast nephropathy, also referred to as light-chain cast nephropathy, is the formation of plugs (urinary casts) in the kidney tubules from free immunoglobulin Immunoglobulin light chain, light chains leading to kidney failure in the context ...
or Systemic Light Chain
Amyloidosis
Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight ...
. There is also increased recognition of paraneoplastic glomerular diseases such as
Membranous Nephropathy
Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (i.e., those of European, Middle Eastern, or North African ancestry.).
It is the seco ...
and
Minimal Change disease
Minimal change disease (also known as MCD, minimal change glomerulopathy, and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein ...
which can be as a result of occult malignancy.
Onco-nephrology also encompasses kidney diseases that are unique to
bone marrow transplant
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce ...
(aka Stem Cell Transplant or SCT) which are frequently seen in
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
patients. Certain kidney diseases associated with SCT include
Graft-Versus-Host Disease
Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.
White blood cells of the donor's immune system which remain wit ...
, sinusoidal Obstruction Syndrome, and
Thrombotic Microangiopathy.
Acute kidney injury in cancer patients
Acute Kidney Injury (AKI) is a commonly feared complication in cancer patients as it can interrupt life saving therapy and potentially have mortality implications. The exact incidence of AKI in this population can vary. In one retrospective study of a single center ICU the risk was as high as 6% and 60 day survival was low as 14% in those requiring dialysis. AKI in this population can be due to volume depletion from vomiting and
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
that occur following chemotherapy or occasionally due to kidney toxicities of chemotherapeutic agents. Less frequently AKI can occur due to obstruction to urine flow from tumor,
lymph node enlargement
Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
, or due to vascular microthrombi as seen in Thrombotic microangiopathies (
i.e. Thrombotic thrombocytopenic purpura,
Atypical hemolytic uremic syndrome
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it can be effectively controlled by interruption of the complement cascade. Particular mo ...
). Newer agents such as anti
Vascular Endothelial Growth Factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, ...
(anti VEGF) are also associated with similar injuries, as well as
proteinuria
Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...
,
hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
and
thrombotic microangiopathy
Thrombotic microangiopathy (TMA) is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury.
It may be seen in association with thrombocytopenia, anemia, purpura and kidney failure.
The classic TMAs are ...
. Additionally, cancer cells can cause AKI by infiltrating the kidney or by precipitating with in the
tubules
In biology, a tubule is a general term referring to small tube or similar type of structure. Specifically, tubule can refer to:
* a small tube or fistular structure
* a minute tube lined with glandular epithelium
* any hollow cylindrical body stru ...
as seen in paraproteinemias.
Chronic kidney disease in cancer patients
With more effective management options for cancer patients, there are far more cancer survivors with residual decline in kidney function from the causes mentioned above. Patients with cancer and CKD have significantly lower survival than the general population. One area of substantial interest is the estimation of kidney function in cancer patients, as it has direct impact on chemotherapy dosing, selection, and eligibility for chemotherapeutics. Overestimating kidney function can lead to overdosing and drug toxicity while underestimating kidney function can prevent patients from receiving key novel therapies. Further studies are necessary to determine the most accurate estimation formula of renal function. Overall, a collaborative approach with oncologists and onconephrologists are important in managing CKD and addressing concerns such as renal replacement therapy and transplant in this population.
Management
Large academic centers in the United States and other countries have started forming an onconephrology related patient approach to manage these complex disorders as above. Therapy can be as simple as limiting offending agents and dose adjustment of chemotherapeutics or as intricate as adding immunosuppressive regimens. Renal Replacement therapy in the form of
hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
and
continuous renal replacement therapy
Hemofiltration, also haemofiltration, is a renal replacement therapy which is used in the intensive care setting. It is usually used to treat acute kidney injury (AKI), but may be of benefit in multiple organ dysfunction syndrome or sepsis. During ...
is also considered in these patients during
acute renal failure
Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.
Causes of AKI are c ...
or diseases leading to
end stage renal disease. Active malignancy is generally a contraindication for
kidney transplantation
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
, but sometimes can be delayed based on the tumor type and risk of reoccurrence. Immunosuppressive therapy use after transplantation can increase risk of malignancies such as skin cancers and rarely cause
Post-Transplant Lymphoproliferative Disorders. Some centers may offer kidney transplantation in the setting of
monoclonal gammopathy of renal significance
Monoclonal gammopathy of renal significance (MGRS) are a group of kidney disorders that present with kidney damage due to nephrotoxic monoclonal immunoglobulins (M proteins) secreted by clonal plasma cells or B cells. By definition, people with ...
but risk of reoccurrence is common.
For these reasons, the role of transplantation continues to be an area of active discussion and expansion.
Specific areas of focus
Topics that are usually of interest to onconephrologists are:
# Electrolyte disorders of malignancy
# Secondary Glomerular diseases of malignancy
# Cancer related renal complications
# Chemotherapy related renal complications
# Myeloma related kidney diseases
# Renal amyloidosis
# Thrombotic Microangiopathy and all its causes and treatment strategies( HUS/TTP)
# Bone marrow transplant related kidney diseases
# Radiation Nephropathy
# Tumor Lysis Syndrome
# Acute Kidney injury in the hospitalized cancer patient.
# The ethics of dialysis in the dying cancer patient
# Dialysis and chemotherapy agents
# Tumor invasion of the kidney
# Obstructive renal disease
# Chronic Kidney disease related to cancer and therapy
# Renal cell cancer
# CKD following nephrectomy
# Targeted therapy and immunotherapy associated kidney toxicities
Training
To be considered an onconephrologist one must complete medical school, an internal medicine residency, and a general nephrology subspecialty training. After general nephrology, one may consider an optional subspecialty training in onconephrology in a few select academic centers that offer the 3rd year track. Centers that offer this training include Memorial Sloan Kettering, MD Anderson, Northwell Health( Hofstra), Mayo Clinic, and the University of Toronto. Currently, no board certification process exists and this additional year of training is optional.
Literature
Several textbooks have been written on this topic. Onconephrology: cancer, chemotherapy and the kidney by Jhaveri and Salahudeen by Springe
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The_American_Society_o
Onconephrology
(ASON)_was_co-founded_on_December_15,_2021_by_Dr._Shruti_Gupta_and_Dr._Kenar_D._Jhaveri._Other_founding_members_include_Dr._Arash_Rashidi_who_will_be_serving_as_treasurer_and_Dr._Biruh_T._Workeneh_serving_as_secretary._The_official_mission_per_their_website_is_"to_promote_research,_clinical_activities,_and_education_related_to_onconephrology."_ASON_also_launched_an_official_twitter_account_under_the_handl
@onconephsociety
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American Society of Onconephrology
The American Society o
Onconephrology
(ASON) was co-founded on December 15, 2021 by Dr. Shruti Gupta and Dr. Kenar D. Jhaveri. Other founding members include Dr. Arash Rashidi who will be serving as treasurer and Dr. Biruh T. Workeneh serving as secretary. The official mission per their website is "to promote research, clinical activities, and education related to onconephrology." ASON also launched an official twitter account under the handl
@onconephsociety
The next Onco-Nephrology Symposium will be held on September 30th, 2022 and hosted by Dana–Farber Cancer Institute">Brigham and Women's Hospital/Dana-Farber Cancer Institute.
References
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Nephrology, Oncology