INTRODUCTION — Cancer is the second leading cause of death in the United States and is associated with significant morbidity [1]. As survival rates of patients with cancer have improved over the past few decades, an increasing number of cancer survivors have or will develop kidney disease associated with malignancy or its treatment. A variety of kidney complications can occur among cancer patients, including acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria and nephrotic syndrome, and electrolyte disorders.
This topic will provide an overview of the major kidney complications that affect patients with cancer. Kidney disease in patients with multiple myeloma or other monoclonal gammopathies, kidney disease among cancer patients who have undergone hematopoietic cell transplantation (HCT), and the nephrotoxicity of specific chemotherapeutic agents are discussed elsewhere:
●(See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation".)
●(See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Treatment and prognosis".)
●(See "Kidney disease following hematopoietic cell transplantation".)
EPIDEMIOLOGY AND PROGNOSIS
AKI in cancer patients — Acute kidney injury (AKI) is a common complication in cancer patients that is associated with reduced treatment dose intensity, lower remission rates, shorter duration of disease control, and increased mortality, hospital length of stay, and cost [2-5]. The incidence of AKI in patients with cancer is likely higher than the incidence observed in patients without cancer.
Overall risk has been addressed in the following observational studies:
●In a Danish population-based study that followed 37,267 incident cancer patients from 1999 to 2006, the one- and five-year risks of AKI, as defined by a >50 percent increase in serum creatinine compared with a baseline serum creatinine measured within one year of cancer diagnosis, were 17.5 and 27 percent, respectively [6]. The risk of AKI was highest in patients with kidney cancer (44 percent), liver cancer (33 percent), and multiple myeloma (32 percent). Kidney replacement therapy (KRT) was required in 5.1 percent of patients within one year of AKI onset.
●In a study of 163,071 patients undergoing systemic treatment of cancer in Ontario, Canada between 2007 and 2014, nearly 1 in 10 patients experienced a hospitalization or received dialysis for AKI [7]. Notably, the annual incidence of AKI increased from 18 to 52 per 1000 person-years over the study period. Malignancies with the highest five-year incidence of AKI were multiple myeloma (26 percent), bladder cancer (19 percent), leukemia (15 percent), and kidney cancer (14 percent). Advanced cancer stage, chronic kidney disease (CKD), and diabetes were all associated with an increased risk of AKI, and AKI risk was accentuated during the 90-day period following systemic therapy.
●In other studies, the risk of AKI was higher in cancer patients who were critically ill [8,9], those receiving treatment for a high-risk myelodysplastic syndrome or acute leukemia [10], recipients of hematopoietic cell transplantation (HCT), and those who had undergone nephrectomy for renal cell carcinoma (RCC) [11,12]. (See "Kidney disease following hematopoietic cell transplantation" and 'AKI after nephrectomy' below.)
Most observational studies have shown that cancer patients who develop AKI, particularly those who require KRT, have a higher risk of mortality than those who do not have AKI [4,8,10,13-15]. In one study of 288 cancer patients admitted to a cancer intensive care unit in Brazil, mortality among patients with RIFLE Risk, Injury, and Failure stages of AKI was 49, 62, and 87 percent, respectively, compared with 14 percent among those without AKI [8]. (See "Definition and staging criteria of acute kidney injury in adults".)
Overall severity of illness, age, and functional status are likely to contribute to the prognosis in these patients, and the presence of cancer should not be considered an absolute exclusion criterion for KRT.
CKD in cancer patients — Chronic kidney disease (CKD) is also a common complication of cancer and its therapy. This may be related in part to the high prevalence of preexisting CKD in patients with various types of malignancy. Two large observational studies, each involving nearly 5000 cancer patients, found that approximately 50 percent of patients with an active malignancy had an estimated glomerular filtration rate (eGFR) of <90 mL/min/1.73 m2 [16,17]. The prevalence of stage 3 and 4 CKD among these patients was 12 and less than 1 percent, respectively. In a prospective study of 4077 patients with various cancers, 30 percent had an eGFR of 45 to 59 mL/min/1.73 m2, and 8.3 percent had an eGFR of <45 mL/min/1.73 m2 [18]. Similar rates of CKD have been reported in other large observational studies of cancer patients [19,20]. (See "Definition and staging of chronic kidney disease in adults".)
Having cancer appears to increase the risk of kidney failure needing kidney replacement therapy (KRT; hemodialysis or peritoneal dialysis, or kidney transplantation). In a Korean population-based cohort study that compared 824,365 patients newly diagnosed with cancer with 1,648,730 patients without cancer who were matched for age, sex, eGFR, hypertension, and diabetes, having cancer was associated with an increased risk of kidney failure requiring KRT after adjusting for multiple variables (adjusted hazard ratio [HR] 2.29, 95% CI 2.20-2.39) [21]. Multiple myeloma was associated with the highest risk of kidney failure requiring KRT (adjusted HR 18.97, 95% CI 14.31-25.15) compared with other cancer types, followed by leukemia, lymphoma, kidney cancer, ovarian cancer, and liver cancer. The contribution of chemotherapy administration, and the specific cytotoxic agents used, was not addressed.
Cancer patients with CKD may have an increased risk of death compared with those without CKD. However, the risk may vary by cancer type, and some studies have found no differences in mortality between cancer patients with and without CKD [18-20,22].
The relationship between CKD and cancer appears to be reciprocal since both CKD and end-stage kidney disease (ESKD) appear to be risk factors for the development of a number of malignancies. A retrospective study of more than 1 million adults assessed the association between severity of kidney disease and the risk of incident cancer [23]. Lower eGFR was associated with an increased risk of kidney cancer (adjusted HR 2.3, 95% confidence interval [CI] 1.8-2.9 for an eGFR of <30 mL/min/1.73 m2) and urothelial cancer but not other cancers. ESRD patients on dialysis have an increased risk for renal parenchymal cancer that is related to the development of acquired renal cystic disease, which increases with time on dialysis [24,25]. (See "Cancer screening in patients on maintenance dialysis" and "Acquired cystic disease of the kidney in adults", section on 'Renal cell carcinoma'.)
ASSESSMENT OF KIDNEY FUNCTION IN CANCER PATIENTS — Patients with cancer require frequent assessment of kidney function to ensure proper dosing of chemotherapeutic agents and to monitor ongoing therapies for evidence of nephrotoxicity. The assessment of kidney function among cancer patients is similar to that in patients without cancer and is discussed elsewhere:
●(See "Assessment of kidney function".)
ACUTE KIDNEY INJURY IN CANCER PATIENTS — Acute kidney injury (AKI) is a common complication among patients with cancer [2,3,6]. The etiologies of AKI in cancer patients include all those that occur in the general population as well as certain etiologies that are specific to the cancer patient population (table 1). These etiologies can be categorized into prerenal, intrinsic renal, and postrenal causes based upon the location of the lesion. However, in many cases, the cause of AKI in cancer patients is multifactorial.
The evaluation of the patient with AKI is presented elsewhere. (See "Evaluation of acute kidney injury among hospitalized adult patients".)
Prerenal causes — The most frequent cause of AKI in cancer patients is prerenal disease, which often results from volume depletion (as a consequence of chemotherapy-related nausea, vomiting, or diarrhea) and/or the use of medications such as diuretics (table 1) [26-28]. Hypercalcemia or the use of medications that affect renal autoregulation, such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or nonsteroidal antiinflammatory drugs, can further exacerbate the risk and severity of prerenal AKI [26-28]. Given the risks of kidney dysfunction, the risk-to-benefit ratio of using any of these agents should be carefully considered in patients with advanced malignancy as well as those who are at high risk of volume depletion during chemotherapy.
●(See "NSAIDs: Acute kidney injury".)
●(See "Clinical manifestations of hypercalcemia", section on 'Renal dysfunction'.)
Among patients who have undergone myeloablative allogeneic hematopoietic cell transplantation (HCT), a hepatorenal-like syndrome secondary to sinusoidal obstruction syndrome (veno-occlusive disease) can occur. (See "Kidney disease following hematopoietic cell transplantation", section on 'Transplant-specific causes' and "Hepatic sinusoidal obstruction syndrome (veno-occlusive disease) in adults".)
Intrinsic renal causes — There are multiple intrinsic renal causes of AKI among patients with cancer (table 1). Etiologies that are specific to patients with cancer are discussed below. (See "Evaluation of acute kidney injury among hospitalized adult patients", section on 'Major causes and classification of AKI'.)
Light chain cast nephropathy (formerly called myeloma kidney) — Light chain cast nephropathy refers to acute or chronic kidney disease (CKD) that results from the overproduction and filtration of toxic light chains, leading to both tubular injury and intratubular cast formation and obstruction. Light chain cast nephropathy is a common cause of AKI among patients with multiple myeloma and is the most common histologic lesion in kidney biopsies of patients with monoclonal gammopathy. It has been rarely reported in patients with other monoclonal gammopathies such as Waldenström macroglobulinemia, lymphoma, and chronic lymphocytic leukemia (CLL).
Tumor lysis syndrome — Tumor lysis syndrome (TLS), considered an oncologic emergency, is caused by massive tumor cell lysis, which releases large amounts of intracellular contents into the systemic circulation, resulting in hyperkalemia, hyperuricemia, hyperphosphatemia, and hypocalcemia. AKI due to TLS results from the formation of crystals composed of uric acid, calcium phosphate, and/or xanthine, which can cause intratubular obstruction, inflammation, and a reduction in glomerular filtration rate (GFR). TLS most often occurs after initiation of chemotherapy in patients with high-grade lymphomas (such as Burkitt lymphoma) or leukemias, although it may develop spontaneously or with treatment of other cancers that have a high proliferative rate or large tumor burden.
●(See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors".)
●(See "Tumor lysis syndrome: Prevention and treatment".)
Tumor infiltration — Metastases to the kidney are not uncommon. However, involvement that is severe enough to impair kidney function requires that both kidneys are involved and occurs mainly with rapidly growing hematologic malignancies, such as lymphoma or acute leukemia [29-31]. Among patients with lymphoma, renal parenchymal infiltration has been reported in up to 60 percent of cases [32-34]; however, most of these cases are undiagnosed [33]. Parenchymal infiltration is usually subclinical, although patients may present with AKI, proteinuria and/or hematuria, and bilaterally enlarged kidneys on imaging. The diagnosis is established by kidney biopsy, although this is not always required. The mechanism by which renal parenchymal infiltration causes AKI is unclear but may involve compression of the renal tubules and microvasculature, leading to tubular obstruction and ischemia. Successful treatment of the primary malignancy with chemotherapy may result in an improvement in kidney function.
Plasma cell infiltration of the kidney can occur in patients with multiple myeloma, but this only rarely causes AKI [32,35,36]. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Less common causes of AKI'.)
Thrombotic microangiopathy — Thrombotic microangiopathy (TMA) is a well-described complication of cancer and its therapy [37-39]. TMA may be associated with the primary cancer or, more likely, with therapeutic regimens such as gemcitabine or vascular endothelial growth factor (VEGF) inhibitors (such as bevacizumab) [39]. TMA may also occur in the setting of HCT, where it is often associated with calcineurin inhibitor use and can coexist with graft-versus-host disease (GVHD) and radiation nephropathy [40].
●(See "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".)
●(See "Pathophysiology of TTP and other primary thrombotic microangiopathies (TMAs)".)
●(See "Drug-induced thrombotic microangiopathy (DITMA)".)
Nephrotoxic anticancer agents — Drug-induced nephrotoxicity is a significant cause of AKI among cancer patients treated with conventional chemotherapeutic agents, targeted therapies, and immunotherapies (table 2) [3,41,42]. These drugs can promote kidney injury through a variety of mechanisms that may affect the glomeruli, tubular segments, interstitium, and/or renal microvasculature [3,41-44]. Importantly, the nephrotoxicity of these agents may be exacerbated by the concurrent or proximate use of other nephrotoxins such as iodinated contrast [45]. As previously noted, drug discontinuation due to nephrotoxicity can limit effective tumor regression and eradication.
The nephrotoxicity of specific anticancer agents is discussed in more detail elsewhere:
●(See "Cisplatin nephrotoxicity".)
●(See "Ifosfamide nephrotoxicity".)
●(See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Renal toxicity'.)
●(See "Intraperitoneal chemotherapy for treatment of ovarian cancer", section on 'Nephrotoxicity'.)
●(See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Kidney'.)
Less common etiologies — Less common causes of intrinsic AKI among cancer patients include the following:
●Lysozymuria – This is a rare disorder that has been observed in patients with acute promyelocytic, monocytic, or chronic myelomonocytic leukemia [46,47]. In these cases, clonal proliferation of mononuclear cells produces large quantities of lysozyme, which is reabsorbed by proximal tubular cells, a process that leads to toxic proximal tubular injury. Elevated serum and urine lysozyme concentrations are suggestive of the diagnosis. Kidney biopsy may show positive staining for lysozyme by immunohistochemistry and accumulation of lysosomes in damaged proximal tubular cells.
●Proliferative/crescentic glomerulonephritis – Both membranoproliferative and rapidly progressive glomerulonephritis have been described in isolated patients with solid tumors and lymphomas, although the etiologic relationship between these conditions is not proven [48,49]. There is some evidence that malignancy is more frequent in patients diagnosed with ANCA vasculitis compared with the general population or with those who have other forms of vasculitis [50]. A high percentage of patients over the age of 50 years who are diagnosed with C3 glomerulopathy have an underlying monoclonal gammopathy. Thus, monoclonal gammopathies should be excluded as the cause in such patients [51].
Postrenal causes — Urinary tract obstruction should be considered as a cause of AKI in cancer patients, especially those with malignancies of the bladder, prostate, uterus, or cervix. Conversely, malignancy should be considered in any patient not known to have cancer who presents with bilateral urinary tract obstruction that is not associated with kidney stones.
Intratubular obstruction — Intratubular obstruction can be caused by crystals composed of uric acid, xanthine, hypoxanthine, or calcium phosphate (in TLS); light chain casts; or crystallization of certain drugs (such as high-dose methotrexate). Maintaining a high urine output with intravenous fluids in "at-risk" patients is the best way to avoid intratubular precipitation in these settings.
●(See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors".)
●(See "Tumor lysis syndrome: Prevention and treatment".)
●(See "Crystal-induced acute kidney injury".)
●(See "Therapeutic use and toxicity of high-dose methotrexate", section on 'Renal toxicity'.)
Extrarenal obstruction — Ureteric obstruction can be caused by a wide range of malignancies (most commonly arising in the gastrointestinal and genitourinary tracts) and usually indicates metastatic disease. The diagnosis is usually established by imaging studies (eg, kidney ultrasound), which typically show dilatation of the collecting system in one or both kidneys (hydronephrosis). Ureteral obstruction due to retroperitoneal tumor or fibrosis (which can be secondary to malignancy) may not be associated with severe hydronephrosis and may require invasive techniques to establish the diagnosis. Patients with cancer may also develop urinary tract obstruction that is unrelated to the malignancy (eg, benign prostatic hyperplasia in men).
●(See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)
●(See "Clinical manifestations and diagnostic evaluation of benign prostatic hyperplasia".)
The clinical spectrum of malignant ureteral obstruction was illustrated by a case series of 102 patients [52]. Obstruction was bilateral in 68 percent of patients. Initial management with a percutaneous nephrostomy or ureteral stent was successful in 95 percent of cases. Despite successful decompression, 53 percent of patients developed complications (mostly, urinary tract infection and obstruction of nephrostomy tubes or stents). Overall survival was poor (median of seven months), reflecting the advanced stage of malignancy in such patients.
Special AKI populations
AKI after hematopoietic cell transplantation — Acute kidney injury (AKI) is a common complication after HCT, occurring in 12 to 66 percent of patients [53]. The risk of AKI depends upon the type of HCT performed (allogeneic versus autologous), the conditioning regimen (myeloablative versus nonmyeloablative) used prior to transplantation, as well the use of nephrotoxic medications and development of GVHD. A more detailed discussion of the causes and management of AKI after HCT is presented elsewhere. (See "Kidney disease following hematopoietic cell transplantation", section on 'Causes of AKI'.)
AKI after nephrectomy — A large percentage of patients with renal cell carcinoma (RCC) have underlying CKD and are at higher risk for postoperative acute kidney injury (AKI) following either radical or partial nephrectomy. Removal of a kidney in such patients is likely to cause AKI because of patients' preexisting kidney disease and diminished kidney functional reserve. Even among patients with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min per 1.73 m2, 33 percent develop AKI after a radical nephrectomy, and postoperative AKI is associated with a 4.2-fold increase in the risk of new-onset CKD at one year after surgery [11]. Among patients undergoing partial nephrectomy, nearly 20 percent develop AKI postoperatively [54]. (See "Definitive surgical management of renal cell carcinoma".)
CHRONIC KIDNEY DISEASE IN CANCER PATIENTS — Patients with cancer may develop chronic kidney disease (CKD) from causes that are related or unrelated to the malignancy and its treatment. Preexisting CKD among cancer patients has important implications for issues such as proper drug dosing and avoidance of potential nephrotoxins.
The management of the complications related to CKD (eg, hypertension, anemia, mineral bone disorder) in cancer patients is broadly similar to that in patients without cancer and is discussed separately. However, erythropoiesis-stimulating agents should be prescribed with caution because of concerns regarding their adverse effects (including higher rates of thromboembolism and faster progression of the underlying disease) in cancer patients.
●(See "Overview of the management of chronic kidney disease in adults".)
●(See "Treatment of anemia in nondialysis chronic kidney disease".)
●(See "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".)
Causes of CKD in cancer patients — The causes of chronic kidney disease (CKD) among cancer patients include all of the causes that are seen in patients without cancer. In addition, kidney insults directly related to cancer or its therapy can lead to progressive CKD. These include:
●Prior episodes of acute kidney injury (AKI) (see 'Acute kidney injury in cancer patients' above)
●Nephrotoxic anticancer agents (see "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: Conventional cytotoxic agents" and "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: Molecularly targeted agents and immunotherapies")
●Reduction in kidney mass following nephrectomy for renal cell (RCC) or urothelial cancers (see 'Patients with renal cell carcinoma' below)
●Chronic obstructive nephropathy (see "Clinical manifestations and diagnosis of retroperitoneal fibrosis" and "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis" and "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults")
●Kidney irradiation
A discussion of the causes, clinical manifestations, and evaluation of CKD is presented in more detail elsewhere. (See "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults".)
Special CKD populations
Patients with renal cell carcinoma — Chronic kidney disease (CKD) occurs commonly in patients with RCC, either as a preexisting condition or as a consequence of treatment [12]. Patients who have localized RCC are typically treated with radical or partial nephrectomy depending upon factors such as the size and location of the tumor as well as the baseline kidney function of the patient. However, patients who undergo nephrectomy for RCC are at risk for developing CKD as a consequence of the reduction in kidney mass and other factors, such as the development of postoperative AKI. Observational studies have shown that the risk of CKD is greater with radical nephrectomy than with partial nephrectomy [55-59]. A clinical scoring system based upon readily available parameters has been developed to identify patients at higher risk of developing significant CKD after nephrectomy [60].
●(See "Overview of the treatment of renal cell carcinoma", section on 'Localized renal cell carcinoma'.)
Among patients who undergo nephrectomy for localized RCC, approximately 25 to 30 percent have preexisting CKD [55,61]. This high prevalence may reflect the presence of risk factors that are common to both RCC and CKD, such as older age, male sex, smoking, obesity, diabetes, and hypertension [11,62-66]. Assessment of the non-neoplastic tissue obtained from tumor nephrectomy specimens may provide important information about the cause of CKD and risk of progression in these patients [67-69]. In one study, medical kidney disease (most frequently, diabetic nephropathy and hypertensive nephropathy) was identified in 15 percent of tumor nephrectomy specimens; 74 percent of these cases also showed evidence of severe arteriolosclerosis [67].
PROTEINURIA OR NEPHROTIC SYNDROME IN CANCER PATIENTS — Patients with cancer may present with proteinuria or the nephrotic syndrome, which can be caused by the underlying malignancy (paraneoplastic) or its treatment. Chemotherapy-associated glomerular diseases may present at various times during treatment, and therefore, patients receiving these drugs (especially therapies targeting the vascular endothelial growth factor [VEGF] pathway as well as immune checkpoint inhibitors) should be monitored for the development of proteinuria and/or kidney function impairment. In addition, proteinuria and the nephrotic syndrome are common presenting features of disorders associated with monoclonal gammopathies. (See "Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects", section on 'Proteinuria/nephrotic syndrome'.)
Paraneoplastic glomerular diseases — The development of proteinuria and of the nephrotic syndrome has been associated with several malignancies (table 3). Among the cancer-associated glomerular diseases, membranous nephropathy (MN) and minimal change disease (MCD) are the most common. An association with malignancy has also been described with membranoproliferative glomerulonephritis, immunoglobulin A (IgA) nephropathy [70], IgA vasculitis (Henoch-Schönlein purpura [HSP]) [71], and amyloid A (AA) amyloidosis [72]. (See "Membranoproliferative glomerulonephritis: Classification, clinical features, and diagnosis", section on 'Rare causes'.)
Membranous nephropathy — MN is the most common glomerular disease in patients with cancer [73,74]. MN may be associated with solid tumors (such as carcinomas of the lung, prostate, or gastrointestinal tract) or, less frequently, with a hematologic malignancy (such as chronic lymphocytic leukemia [CLL]); it may also occur after hematopoietic cell transplantation (HCT). (See "Membranous nephropathy: Pathogenesis and etiology", section on 'Malignancy' and "Kidney disease following hematopoietic cell transplantation", section on 'Nephrotic syndrome'.)
Treatment of the cancer is often associated with improvement of the kidney disease. Patients diagnosed with MN should undergo routine cancer screening. These issues are discussed in detail separately. (See "Membranous nephropathy: Clinical manifestations and diagnosis", section on 'Screening for malignancy'.)
Minimal change disease — MCD may occur in association with Hodgkin lymphoma and, less commonly, other lymphoproliferative disorders as well as solid tumors. One putative mechanism is secretion of a glomerular-toxic lymphokine by abnormal T cells. Lymphoma-associated MCD is frequently resistant to treatment with glucocorticoids and cyclosporine [75,76]; therefore, a poor response to the treatment of MCD with these agents should prompt an investigation for an underlying malignancy. In some but not all patients with lymphoma-associated MCD, the course of MCD correlates with that of the lymphoma. (See "Minimal change disease: Etiology, clinical features, and diagnosis in adults", section on 'Malignancies'.)
Chemotherapy-associated glomerular disorders — A number of agents used in the treatment of cancer have been associated with the development of proteinuria and/or the nephrotic syndrome. Kidney biopsy is recommended in these cases to determine the associated pathology and to guide therapy. These include the following:
●Bisphosphonates – Collapsing focal segmental glomerulosclerosis (FSGS) has been associated with exposure to high doses of intravenous bisphosphonates, particularly pamidronate, in patients with cancer. Such patients typically present with nephrotic syndrome and kidney failure. Stopping the bisphosphonate may improve kidney function, but most patients have residual kidney disease, and some progress to end-stage kidney disease (ESKD). (See "Risks of therapy with bone antiresorptive agents in patients with advanced malignancy", section on 'Proteinuria and kidney injury'.)
●Interferons – Chronic therapy with interferon-alpha, -beta, or -gamma has been associated with the development of FSGS not otherwise specified (NOS), collapsing FSGS, and MCD. The onset of proteinuria and/or nephrotic syndrome may occur days to years after the initiation of interferon treatment. Discontinuation of interferon generally leads to complete remission of nephrotic syndrome in patients with MCD; however, remission is less consistent in those with collapsing FSGS or FSGS NOS.
●Mechanistic (previously called mammalian) target of rapamycin (mTOR) inhibitors – Sirolimus has been associated with proteinuria and collapsing FSGS. In addition, rare cases of membranoproliferative glomerulonephritis, MN, and IgA nephropathy have reported in patients treated with sirolimus. (See "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors", section on 'Proteinuria'.)
●Immune checkpoint inhibitors – Antibody-induced lupus nephritis has been reported in patients treated with the checkpoint inhibitor, ipilimumab [77]. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Kidney'.)
Disorders associated with monoclonal gammopathy — Proteinuria or nephrotic syndrome can occur in patients who have multiple myeloma or other monoclonal gammopathies. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Albuminuria or nephrotic syndrome'.)
Amyloidosis — Amyloidosis is a group of diseases characterized by the extracellular deposition of Congo red-positive fibrils in soft tissues. In immunoglobulin (Ig)-associated amyloidosis, the fibrils can consist of monoclonal light chains (AL), heavy chains (AH), or both light and heavy chains (AHL). AL amyloidosis is by far the most common, accounting for more than 94 percent of cases [78]. Patients with Ig-associated amyloidosis typically present with proteinuria and nephrotic syndrome as well as kidney function impairment. (See "Renal amyloidosis" and "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis".)
Monoclonal immunoglobulin deposition disease — Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the deposition of nonamyloid monoclonal light and/or heavy chains within basement membranes. MIDD is pathogenetically similar to Ig-associated amyloidosis except that the light (or heavy) chain fragments do not form fibrils, and the deposits are Congo red negative. Three subtypes of MIDD have been reported based upon the composition of the deposits: light chain deposition disease (LCDD), heavy chain deposition disease (HCDD), and light and heavy chain deposition disease (LHCDD). MIDD is most frequently associated with multiple myeloma but can also occur in patients with Waldenström macroglobulinemia, CLL, and nodal marginal zone lymphoma [79,80]. MIDD typically presents with proteinuria, kidney function impairment, and hypertension.
●(See "Monoclonal immunoglobulin deposition disease".)
Less common causes — Other monoclonal gammopathy-associated disorders that can cause proteinuria and nephrotic syndrome include the following:
●Monoclonal cryoglobulinemia. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Less common causes of albuminuria'.)
●Membranoproliferative glomerulonephritis (eg, proliferative glomerulonephritis with monoclonal immunoglobulin deposition [PGNMID], C3 glomerulopathy associated with monoclonal gammopathy).
●Crystalline podocytopathy. (See "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Less common causes of albuminuria'.)
●Fibrillary glomerulonephritis and immunotactoid glomerulopathy. (See "Glomerular diseases due to nonamyloid fibrillar deposits".)
●Membranous-like nephropathy with masked immunoglobulin G (IgG)-kappa. (See "Membranous nephropathy: Pathogenesis and etiology", section on 'Membranous-like nephropathy with masked IgG-kappa'.)
ELECTROLYTE DISORDERS IN CANCER PATIENTS — Electrolyte disorders are commonly seen in patients with malignancies, and in many cases, the etiologies of these disorders are the same as those seen in the general population. In other circumstances, electrolyte disorders can be caused by the cancer (ie, paraneoplastic syndromes) or its treatment.
Hyponatremia — Hyponatremia is the most common electrolyte disorder encountered in patients with malignancy, occurring in up to 47 percent of hospitalized cancer patients [81,82]. Hyponatremia in these patients is associated with increased hospital length of stay, increased mortality, and poor response to therapy [83]. The causes of hyponatremia among cancer patients include all of the causes of hyponatremia among patients without cancer. There are two major mechanisms of hyponatremia in patients with cancer:
●Hypovolemia due to gastrointestinal fluid losses, poor oral intake, and/or effective circulating volume depletion (such as with third-spacing of fluids, heart failure, or cirrhosis). (See "Causes of hypotonic hyponatremia in adults".)
●Syndrome of inappropriate antidiuretic hormone (SIADH). SIADH may result from the ectopic production of antidiuretic hormone (ADH) by malignancies such as small-cell cancer of the lung, head and neck tumors, and primary or secondary brain tumors. In addition, SIADH can be induced by high-dose intravenous cyclophosphamide and the vinca alkaloids, vincristine or vinblastine.
In patients with SIADH, the aggressive hydration administered with certain chemotherapy regimens may worsen hyponatremia, and the serum sodium must be closely monitored. Water restriction can be problematic in cancer patients, particularly for those with stomatitis or other difficulties in maintaining oral hydration and nutrition, and should be prescribed with caution.
Rarely, hyponatremia is reported as a side effect of several molecularly targeted chemotherapeutic agents. (See "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: Conventional cytotoxic agents" and "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: Molecularly targeted agents and immunotherapies".)
The evaluation and treatment of hyponatremia are presented elsewhere. (See "Diagnostic evaluation of adults with hyponatremia" and "Overview of the treatment of hyponatremia in adults".)
Hypernatremia — Diabetes insipidus, with polyuria and polydipsia, can occur in patients with cancer. Hypernatremia will develop if the patient does not have access to or cannot drink water:
●Primary or secondary malignancies in the brain (most often, lung cancer, leukemia, or lymphoma) can involve the hypothalamic-pituitary region and lead to central diabetes insipidus; neurosurgery for brain tumors is also an important cause. (See "Clinical manifestations and causes of central diabetes insipidus", section on 'Cancer'.)
●Hypercalcemia in patients with cancer can lead to reversible nephrogenic diabetes insipidus. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus", section on 'Hypercalcemia' and "Hypercalcemia of malignancy: Mechanisms".)
Less commonly, ectopic production of adrenocorticotropic hormone (ACTH) by tumor cells (in the setting of severe Cushing's syndrome) can cause hypernatremia [84,85].
The evaluation and treatment of hypernatremia are discussed elsewhere. (See "Etiology and evaluation of hypernatremia in adults" and "Treatment of hypernatremia in adults".)
Hypercalcemia — Hypercalcemia is a relatively common complication of malignancy that is most often caused by the release of parathyroid hormone-related peptide (PTHrP) or local osteolysis (mediated by cytokines) (table 4) [86]. Rarely, hypercalcemia is due to ectopic production of 1,25-dihydroxyvitamin D (calcitriol) in patients with lymphoma. Tumors that secrete PTHrP include squamous cell carcinomas; renal cell carcinoma (RCC); adenocarcinomas of the breast, prostate, and ovary; and certain lymphomas. Local osteolytic mechanisms are seen with multiple myeloma, lymphomas, and breast cancer. (See "Hypercalcemia of malignancy: Mechanisms".)
PTHrP shares the same N-terminal end as parathyroid hormone (PTH) and can bind to the same receptor, the type 1 PTH receptor. As a result, PTHrP can simulate most of the actions of PTH, including increases in bone resorption and distal tubular calcium reabsorption and inhibition of proximal tubular phosphate transport [87].
Treatment of cancer-associated hypercalcemia centers on aggressive intravenous hydration to increase renal calcium excretion and treat concomitant volume depletion, followed by therapy with either a bisphosphonate, calcitonin, or denosumab to decrease bone release of calcium [86]. Glucocorticoids may be used in patients with lymphoma and endogenous overproduction of calcitriol. (See "Treatment of hypercalcemia".)
An abnormal total serum calcium concentration in the presence of a normal ionized calcium concentration (pseudohypercalcemia) can occur in patients with multiple myeloma. (See "Relation between total and ionized serum calcium concentrations", section on 'Multiple myeloma'.)
Hypokalemia — Hypokalemia can result from gastrointestinal losses (due to vomiting or diarrhea induced by chemotherapy) or from renal losses (due to ifosfamide, cisplatin, or diuretics, or, in some patients with leukemia, associated with lysozymuria) [88,89]. Hypokalemia may also be caused by the paraneoplastic secretion of ectopic adrenocorticotropic hormone (ACTH) in the setting of neuroendocrine tumors, most commonly arising in the lung (bronchial carcinoid tumors), small-cell lung cancer, lung adenocarcinomas, and medullary thyroid tumors [90]. (See "Causes of hypokalemia in adults".)
Spurious hypokalemia (pseudohypokalemia) may occur in patients with a large number of metabolically active blood cells, such as those with acute myeloid leukemia and a marked leukocytosis. (See "Causes of hypokalemia in adults", section on 'Increased blood cell production'.)
Hyperkalemia — Hyperkalemia may result from kidney failure of any cause or tumor lysis syndrome (TLS), which is also accompanied by hyperphosphatemia, hypocalcemia, and hyperuricemia. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors", section on 'Clinical manifestations'.)
Of particular importance in this patient population is pseudohyperkalemia, usually in the setting of marked leukocytosis or thrombocytosis [91]. This is due to a shift of potassium out of platelets or leukocytes after a blood draw and when a blood clot has formed. The measurement of a plasma sample, rather than a serum sample, for potassium levels should be considered in the patient with marked thrombocytosis or leukocytosis to avoid this occurrence. (See "Causes and evaluation of hyperkalemia in adults", section on 'Pseudohyperkalemia'.)
Hypophosphatemia — Hypophosphatemia can occur in cancer patients who develop proximal tubular dysfunction due to toxic light chains in multiple myeloma. In such patients, hypophosphatemia may be accompanied by other abnormalities including glucosuria, hypouricemia, aminoaciduria, and renal tubular acidosis (Fanconi syndrome). (See "Hypophosphatemia: Causes of hypophosphatemia", section on 'Fanconi syndrome' and "Kidney disease in multiple myeloma and other monoclonal gammopathies: Etiology and evaluation", section on 'Light chain proximal tubulopathy'.)
Hypophosphatemia is also a common side effect of imatinib, a molecularly targeted agent that is used for treatment of chronic myelogenous leukemia, and gastrointestinal stromal tumors. (See "Chemotherapy nephrotoxicity and dose modification in patients with kidney impairment: Molecularly targeted agents and immunotherapies", section on 'Imatinib'.)
A rare and indolent condition that leads to hypophosphatemia is the syndrome of tumor-induced osteomalacia or oncogenic osteomalacia in which tumor production of phosphaturic factors, such as fibroblast growth factor (FGF)-23, results in renal phosphate wasting and osteomalacia [92]. Most of the malignancies associated with this syndrome are mesenchymal tumors (ie, chondrosarcoma, osteoblastoma, and solitary fibrous tumor/hemangiopericytoma). The mainstay of therapy for this syndrome is tumor resection, although monoclonal antibodies targeting FGF-23 may prove to be an effective alternative. (See "Hereditary hypophosphatemic rickets and tumor-induced osteomalacia", section on 'Tumor-induced osteomalacia'.)
Hyperphosphatemia — Hyperphosphatemia can occur in patients with TLS and is caused by the release of intracellular phosphate from lysed tumor cells. (See "Tumor lysis syndrome: Pathogenesis, clinical manifestations, definition, etiology and risk factors", section on 'Hyperphosphatemia' and "Overview of the causes and treatment of hyperphosphatemia", section on 'Tumor lysis syndrome'.)
In patients with multiple myeloma and Waldenström macroglobulinemia, circulating monoclonal proteins can interfere with the laboratory measurement of phosphate, resulting in spuriously elevated serum phosphate levels (pseudohyperphosphatemia). (See "Overview of the causes and treatment of hyperphosphatemia", section on 'Pseudohyperphosphatemia'.)
Hypomagnesemia — Tubular dysfunction due to chemotherapy drugs, particularly cisplatin, ifosfamide, and the inhibitors of the epidermal growth factor receptor (EGFR) pathway, can lead to urinary magnesium wasting and hypomagnesemia. Particularly with cisplatin, this can persist for years after drug administration.
●(See "Cisplatin nephrotoxicity", section on 'Hypomagnesemia'.)
●(See "Hypomagnesemia: Causes of hypomagnesemia".)
●(See "Hypomagnesemia: Causes of hypomagnesemia", section on 'Medications'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults" and "Society guideline links: Cancer of the kidney and ureters".)
SUMMARY
●A variety of kidney complications can occur among cancer patients, including acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria and nephrotic syndrome, and electrolyte disorders. (See 'Introduction' above.)
●Patients with cancer require frequent assessment of kidney function to ensure proper dosing of chemotherapeutic agents and to monitor ongoing therapies for evidence of nephrotoxicity. The assessment of kidney function among cancer patients is similar to that in patients without cancer. (See 'Assessment of kidney function in cancer patients' above.)
●AKI is a common occurrence in patients with cancer. In general, the same etiologies of AKI that occur in the general population can affect cancer patients; however, certain causes of AKI are specific to the cancer patient population. AKI in cancer patients can be divided into prerenal, intrinsic renal, or postrenal causes. (See 'Prerenal causes' above and 'Intrinsic renal causes' above and 'Postrenal causes' above.)
●Patients with cancer may develop CKD from causes that are related or unrelated to the malignancy and its treatment. Kidney insults directly related to cancer or its therapy include prior episodes of AKI, nephrotoxic anticancer agents, a reduction in kidney mass following nephrectomy for renal cell (RCC) or urothelial cancers, chronic obstructive nephropathy, and kidney irradiation. (See 'Causes of CKD in cancer patients' above.)
●Patients with cancer may present with proteinuria and the nephrotic syndrome, which can be caused by the underlying malignancy (paraneoplastic) or its treatment. The most common paraneoplastic glomerular diseases are membranous nephropathy (MN) and minimal change disease (MCD). Proteinuria and nephrotic syndrome may be the presenting features of disorders associated with monoclonal gammopathies, including amyloidosis and monoclonal immunoglobulin deposition disease (MIDD). Chemotherapy-associated glomerular diseases may present at various times during treatment, and therefore, patients receiving these drugs should be monitored for the development of proteinuria and/or kidney function impairment. (See 'Paraneoplastic glomerular diseases' above and 'Chemotherapy-associated glomerular disorders' above and 'Disorders associated with monoclonal gammopathy' above.)
●Electrolyte disorders are commonly seen in patients with malignancies, and in many cases, the etiologies of these disorders are the same as those seen in the general population. In other circumstances, electrolyte disorders can be caused by the cancer (ie, paraneoplastic syndromes) or its treatment. Common abnormalities include hyponatremia, hypernatremia, hypercalcemia, hypokalemia, hyperkalemia, hypophosphatemia, hyperphosphatemia, and hypomagnesemia. (See 'Hyponatremia' above and 'Hypernatremia' above and 'Hypercalcemia' above and 'Hypokalemia' above and 'Hyperkalemia' above and 'Hypophosphatemia' above and 'Hyperphosphatemia' above and 'Hypomagnesemia' above.)
