In a study of 4864 adult, solid cancer patients having the five most frequently occurring types of cancer (breast, colorectal, lung, ovarian, and prostate), it was reported that 57.4 and 52.9 % of patients had an abnormal creatinine clearance of less than 90 mL/min when calculated with the Cockcroft–Gault formula and the modification of diet in renal disease (MDRD) formula, respectively [6] . Similarly, in a more recent study of 1218 adult, solid cancer patients receiving chemotherapy, 64.0 % were found to have a decreased GFR of less than 90 mL/min/1.73 m². Since different cancer types behave differently and their treatments are different, all cancer patients, regardless of the type of cancer, were found to have increased risk of renal insufficiency [7]. Both studies suggest that the frequency of renal insufficiency is routinely underestimated when the physician bases their judgment on the serum creatinine alone. Thus, renal function must be estimated with formulas which take into account gender, age, and weight of an individual [6, 7]. In addition, both studies excluded those with multiple myeloma and hematologic malignancies. Had these populations been included, the burden of CKD would evidently have been higher .

In patients with multiple myeloma, impaired renal function is present in more than 20–30 % of the population at the time of diagnosis [8, 9]. At some point in their disease course, approximately 50 % of them may develop acute kidney injury (AKI) or CKD [9] . Renal failure was more prevalent in those who had more severe hypercalcemia, anemia, and Bence Jones proteinuria [9]. Reversibility of renal failure depended on serum creatinine levels, presence of hypercalcemia, and the extent of proteinuria [8]. Survival was significantly less in those who had renal failure as compared to those with normal renal function, with median survival ranging from 4 months to 1 year, as shown in another study [8] .

HSCT is performed more frequently for various hematologic malignancies . CKD following HSCT has been shown to be relatively common and occurring in approximately 16.6–23 % of HSCT patients [10–12]. Some literature suggests higher rates depending on definition of CKD. Risk factors for CKD in this population included: AKI, total body irradiation, graft versus host disease, and long-term calcineurin inhibitor use [10] .

Studies over the past 30 years have suggested an increased risk of developing cancer in patients with ESKD . Population based studies have also shown an association of mild to moderate CKD and an increased risk of cancer. Potential reasons for this increased risk include the presence of chronic urinary tract infections, a weakened immune system, prior treatment with cytotoxic or immunosuppressant drugs, nutritional deficiencies, and impaired DNA repair mechanisms. Other risks include the environmental exposures leading to cancer and renal failure or acquired cystic renal disease [13, 14].

Cancer rates are higher in patients with ESKD on hemodialysis compared to the general population. In a retrospective analysis of over 800,000 patients on dialysis over an average follow up of 2.5 years, the standardized incidence ratio of cancer was 1.18. Kidney, bladder, thyroid, and Kaposi’s sarcoma had the highest risks. Patients on dialysis have increased risk of lower urinary tract disease and are more susceptible to viral carcinogenesis (e.g., hepatitis B and C). The risk of kidney cancer increases with increased time on dialysis . This seems to be secondary to acquired cystic renal disease associated carcinoma. Other risk factors for cancer include dialysis-induced immune dysfunction, prolonged analgesic abuse, and carcinogenesis from prior immunosuppressive or cytotoxic therapy. ESKD after stem cell transplant is associated with increased mortality compared to ESKD from other causes. The cancer risk after starting dialysis has been shown to increase from 10 to 80 %. [15, 16]. Of a cohort of 831,804 patients on dialysis in the USA, Europe, Australia, and New Zealand, 3 % developed cancer after 2.5 years of follow up [14]. There was a higher risk of cancer in patients younger than 35 [14]. In addition, there was a high risk of kidney, bladder, thyroid, and other endocrine organs [14]. Activation and exposure to viruses such as hepatitis B and C, Epstein–Barr virus, and human papillomavirus likely accounted for the increased risk of other types of cancer. Contrary to bladder cancer, the risk of kidney cancer increased with time on dialysis. Acquired renal cystic disease on dialysis may contribute to this risk. There was difference in risk for cancer between hemodialysis and peritoneal dialysis. Higher rate of cancer was detected in Australia and New Zealand versus Europe and the USA. However, this may be the result of ascertainment bias given the under reporting of cancer in the latter . In another analysis from three large dialysis registries in the USA, Europe, and Australia, cancers of the kidney and bladder were more common, and there was increased risk relatively in the younger population and the female patients [13]. In a study of 28,855 patients who were on dialysis, there was a fourfold increase in ESKD related cancers, namely kidney, urinary tract, and thyroid cancers and a smaller yet still increased risk of cancers, 20 related to immune deficiency [16]. For all cancers, the risk was higher in the individuals less than 50 years old [16] .

Studies on the CKD population have been conducted to determine the association of CKD and cancer risk in the older population. One such study from Australia demonstrated that men with CKD had an increased risk for cancer. This risk for men began at an eGFR of 55 ml/min/1.73 m², and posed a greatest risk when eGFR was less than 40 ml/min/1.73 m². Men with CKD were more at risk for lung and urinary tract cancers [17]. In a more recent analysis, eGFR < 60 mL/min/1.73 m² appears to be a significant risk factor for death from cancer [18]. The excess cancer mortality in those with reduced kidney function varied with site, with the greatest risk in those with breast and urinary tract cancer [18]. Each decrease in eGFR by 10 ml/min/1.73 m² increased the risk of cancer by 29 % in men. Lung and urinary tract cancers comprised most of the excess cancer risk. Residual confounding (e.g., occupational exposures) was speculated to explain the lack of increased cancer risk in women with CKD .[18]

CKD is also a significant risk factor for both cardiovascular and noncardiovascular mortality in patients with cancer. Fried et al. were one of the first to show an increase in cancer mortality in patients with decreased renal function [19]. Among 4637 patients in the Cardiovascular Health Study, patients with cystatin C levels in the fourth quartile versus the first quartile had a 79 % increase in cancer mortality rate. The IRMA study was a French observational study that included 4684 patients with cancer, of which 53 % had a eGFR less than 90 ml/min/1.73 m² and 12 % had an eGFR less than 60 ml/min/1.73 m² [20]. Patients with CKD stage 3 or lower had a 27 % higher mortality. Over one half of these patients required a dose adjustment of chemotherapy, reflecting a practical impact of CKD on this population. In another study of 8223 patients in Korea, CKD was an independent predictor of cancer-specific mortality, which remained significant in a multivariate model [21]. Iff et al. studied 4077 patients in the Blue Moutains Eye Study and found an 18 % increase in mortality for every 10 ml/min/1.73 m² reduction in eGFR [18]. Breast and urinary tract cancers conferred the greatest risk of mortality among patients with CKD. The largest study to date included a cohort of 123,717 patients with a median follow up of 7 years [22]. Patients with CKD had a 20 % increase in cancer mortality compared to patients with normal renal function. Baseline CKD was associated with an increased risk of hepatic, renal, and urinary tract malignancies. Poor nutrition, increased oxidative stress, proinflammatory state, and procoagulant state were proposed as mechanisms for the increased cancer risk in these patients .

Proteinuria is also associated with the development of cancer. In a 10 year follow up of 5425 patients without diabetes or macroalbuminuria, each standard deviation of albuminuria (log of albumin to creatinine ratio) was associated with a 20 % increased risk cancer [23]. Patients with the highest quintile of albumin-to-creatinine ratio compared to the lowest quintile had a relative risk of 8.3 and 2.4 for the development of bladder and lung cancer, respectively .

In the general population, there is some controversy as to whether routine screening for CKD by blood work and/or urine testing is cost-effective . However, it should be a priority to define and grade CKD in cancer patients, by checking a serum creatinine and estimating GFR. Since kidney plays a pivotal role in drug elimination, having a good estimate of kidney function is essential for proper drug dosing especially that of many chemotherapeutic agents.

In addition, as stated earlier, CKD is an independent risk factor for cardiovascular disease, progression to ESKD, and all cause mortality [25–28]. This in itself can be helpful at preventative behaviors.

GFR can be measured directly by measuring renal excretion of radioisotopes or by nuclear renogram. Whereas these measures are highly accurate and directly measure GFR, they are expensive and not often readily available. A more common method to ascertain kidney function is by estimating the GFR through one of several available estimating equations. These equations use readily available variables such as serum creatinine, age, gender, weight, and race and are listed in Table 2.2.

The Cockcroft–Gault is the most commonly used equation and the modified Jelliffe formula is used in several oncology trials for the purpose of estimating GFR. Recently, the MDRD equation has gained popularity, but was derived in a healthy population, and is currently not recommended for use in the oncology patient . Based on recent literature comparing various GFR-estimating equations in oncology patients, it is currently recommended to use the Cockcroft–Gault equation [29]. If the GFR is greater than equal to 50 ml/min and the patient is greater than 70 years and/or BMI greater than equal to 30, the Wright formula gives the best estimate of GFR [24] (See Table 2.2) .

Microalbuminuria is defined at 30–300 mg/day of urine albumin and thus is not detected by a urine dipstick test alone. Urine protein is comprised of albumin and Tamm-–Horsfall proteins. In certain hematological malignancies, light chains are also excreted in the urine, called Bence Jones proteins. This abnormal proteinuria is not detected by urine dipstick test.

Checking urine for microalbumin is a simple and important tool to detect individuals with early or undiagnosed CKD. When microalbuminuria is present, GFR is typically elevated, normal, or slightly impaired [30]. Microalbuminuria is defined as 30–300 mg/day of urine albumin, and macroalbuminuria is defined as greater than 300 mg/day of urine albumin. Following are the ways to check for microalbuminuria/proteinuria: (1) urine albumin-to-creatinine ratio (ACR), (2) urine protein-to-creatinine ratio (PCR), (3) reagent strip urinalysis for total protein with automated reading, and (4) reagent strip urinalysis for total protein with manual reading. In all of the above, an early morning urine sample is preferred, and the test should always be confirmed [2].

Albuminuria is not only important for detecting CKD, but its significance in long-term prognosis bears relevance. It is associated with increased all-cause and cardiovascular mortality, as well as progression to end-stage renal disease. These risks exist even in the absence of a reduced GFR [31] .