Nephrol Dial Transplant, 2024, 39, 920–928

[Link]
Advance access publication date: 10 February 2024

Global epidemiology of kidney cancer

REVIEW

1
Luigi Cirillo , Samantha Innocenti1 and Francesca Becherucci 1 ,2

1
Nephrology and Dialysis Department, Meyer Children’s Hospital IRCCS, Florence 50139, Italy
2
Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence, Italy
Correspondence to: Luigi Cirillo; E-mail: [Link]@[Link]

Watch the video of this contribution at [Link]

ABSTRACT

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Kidney cancer (KC) is a disease with a rising worldwide incidence estimated at 400 000 new cases annually, and a worldwide mortality
rate approaching 175 000 deaths per year. Current projections suggest incidence continuing to increase over the next decade, empha-
sizing the urgency of addressing this significant global health trend. Despite the overall increases in incidence and mortality, striking
social disparities are evident. Low- and middle-income countries bear a disproportionate burden of the disease, with higher mortality
rates and later-stage diagnoses, underscoring the critical role of socioeconomic factors in disease prevalence and outcomes. The ma-
jor risk factors for KC, including smoking, obesity, hypertension and occupational exposure to harmful substances, must be taken into
account. Importantly, these risk factors also often contribute to kidney injury, a condition that the review identifies as a significant, yet
under-recognized, precursor to KC. Finally, the indispensable role of nephrologists is underscored in managing this complex disease
landscape. Nephrologists are at the forefront of detecting and managing kidney injuries, and their role in mitigating the risk of KC is
becoming increasingly apparent. Through this comprehensive analysis, we aim to facilitate a more nuanced understanding of KC’s
epidemiology and determinants providing valuable insights for researchers, clinicians and policymakers alike.

Keywords: CKD, renal cell carcinoma, risk factors, social disparities, statistics

INTRODUCTION prevalence figures (323 000 and 822 000 people, respectively) [1].
This is in line with the worldwide incidence, mortality and their
Kidney cancer (KC) shows complex and multifaceted global epi-
ratio (i.e. mortality/incidence ratio, M/I). In particular, an M/I < 1
demiological patterns that remain an issue of significant concern.
indicates that fewer people died from a particular cancer than
This review embarks on a comprehensive survey of KC’s statistics
those who were diagnosed, in a given year, increasing the number
and its determinants, shedding light on geographic, social and bio-
of prevalent cases in next the year. In 2020, the M/I for KC was
logical factors. We underline the instrumental role of kidney dis-
0.39, significantly lower than that reported for pancreatic cancer
eases (KD) in determining KC, from an epidemiological perspec-
(0.94), which is characterized by one of lowest life expectancy at
tive. The wide-ranging exploration of KC’s global epidemiology un-
5 years. In contrast, prostate and testis cancer, which follow af-
derscored here highlights the crucial role of nephrologists in its
ter KC, had both an M/I of 0.26 [1]. In pediatric patients the Inter-
prevention, identification and management.
national Classification of Childhood Cancer Consortium reported
KC representing 5% of all childhood cancers (under 18 years of
age) [3]. In children, Wilms Tumor (WT) is the most common type
GLOBAL EPIDEMIOLOGY OF KIDNEY of KC, together with rhabdoid renal tumor and sarcomas; WT
CANCER accounts for over 90% of all KC in each age from 1 to 7 years
Geographic distribution and the proportion of renal carcinomas increases gradually with
The 2020 Globocan Registry indicates KC as the 12th most com- age [3].
mon cancer worldwide, with 1.2 million prevalent cases over In 2020, the worldwide incidence age-standardized rate (ASR)
5 years (Fig. 1). As a global picture, the three cancers with the of KC was 4.6 per 100 000 people, representing the 16th highest
highest incidence are breast, colorectal and prostate cancers, with incident cancer. The incidence ASR was higher for males (6.1 per
7.7, 5.2 and 4.9 million prevalent cases, respectively. The KC preva- 100 000) than for females (3.2 per 100 000), with the highest rates
lence is slightly different in males and females (9th and 14th most observed in countries with very high human development index
frequent cancer, respectively) [1]. Clear cell renal carcinoma rep- (HDI) scores. HDI is a composite index of life expectancy, educa-
resents the most frequent type in adults [2]. In this section on the tion, and per capita income indicators, which is used to rank coun-
updated data of KC statistics, we pinpoint its global disparities tries into four tiers of human development. North America, Aus-
across regions and the paradox of higher incidence yet better sur- tralia, New Zealand and Northern Europe had the highest inci-
vival rates in more economically developed countries, all of which dence (12.2–10.3 per 100 000), while Middle Africa, Melanesia and
will be discussed in the following analysis. South-Central Asia had the lowest (1–1.4 per 100 000). This ge-
Globally, the USA and China reported the highest number of ographical distribution suggests a link to national income also,
cases, more than double those of Japan, the third-highest country. with the ASR in high-income countries being more than double
In 2020, the KC 5-year prevalence exceeded the 1-year and 3-year that in middle and low-income countries (9.6 vs 3.9 per 100 000)

Received: August 4, 2023; Editorial decision: January 16, 2024

© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.
All rights reserved. For permissions, please e-mail: [Link]@[Link]
 L. Cirillo et al. | 921

A B
Northern Europe Others Eastern Asia
12.2 Incidence
5.5% 6.9% 24.1%
(66,430) (83,341) (291,226) Mortality

ASR (World) per 100,000

10.3 10.3
10 9.7 9.5
South
8.3
America
6.0%
(72,753)
5.3 5.2
Southern 5
4.1 4 3.9
Europe 3.4
6.6% 2.7 2.8
2.4
2.7 2.6 2.5
2.1 2.3 2.1 2 2.1
(79,349) 1.6 1.8 1.8 1.7 1.7 1.6
1.2 1.3 1.2 1.2 1.2 1.2 1.4 1.2
0.88 0.82 0.72
Western
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So
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(138,320) (236,259)

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Figure 1: Left panel: global prevalence of KC for different world areas according to Globocan 2020; crude numbers in round brackets. Right panel: KC
incidence and mortality worldwide according to Globocan 2020; data are expressed as ASR per 100 000 world population [1].

[1] (Fig. 1). In children, the incidence ASR of KC is 8.3 per million, Worldwide, the number of newly diagnosed KC cases has con-
being highest in North America and Europe (9–10 per million) and sistently risen from 207.3 thousand in 1990 to 393.0 thousand
lowest in most Asian regions (4–5 per million) [3]. The cumulative in 2017, with incidence ASR slightly increasing from 4.72 per
incidence risk of KC from birth to age 74 years was 0.52%, mean- 100 000 to 4.94 per 100 000 over the same period. Certain countries,
ing that over half a percent of the population would be expected such as the Czech Republic, have observed the highest incidence
to develop KC within that age range [1]. rates, while most African and Asian populations have seen the
KC has a worldwide ASR mortality of 1.8 deaths per lowest [1].
100 000/year (Fig. 1), with higher rates in males (2.5 per Incidence rates have been increasing in most countries, more
100 000/year) than in females (1.2 per 100 000/year) (Fig. 2) (1). notably in Central and South America and in some Asian coun-
Like incidence, mortality rates were higher in very high and high tries, whereas in Africa, no significant changes in incidence have
HDI countries, and the cumulative mortality risk from birth to age been observed in the last decade. In Northern America, both
74 years was 0.20% [1]. When examining broader global regions, Canada and the USA have seen an increase in incidence rates,
Central and Eastern Europe showed the highest mortality ASR (3.4 especially within the US Black population. European countries
per 100 000/year), compared with South-East Asia, which reported present varied incidence trends: in particular, Eastern Europe reg-
the lowest (0.61 per 100 000/year) (Fig. 1) (1). istered the highest increase in new cases [1].
For children younger than 20 years of age with WT, the 5-year By 2030, the global number of KC cases is projected to increase
relative survival rate is 93% [4]. further to 475.4 thousand [6] (Fig. 2). However, the incidence ASR
To better understand the epidemiology, it is important to con- is predicted to slightly decrease to 4.46 per 100 000 [2]. Also, in
sider that in 2020 the M/I varied by country, with high income pediatric patients, despite scarce available data, the incidence of
countries reporting a M/I 0.3, while low income countries 0.66 [1]. KC in the pediatric population was stable for WT (average annual
High-income regions report a paradoxical trend: elevated KC rates % change 0.1) from 1996 to 2010, and increased for renal carci-
alongside lower M/I ratios. Such a relationship underscores the nomas in children and adolescents (average annual % change 3.7
pivotal influence of a nation’s overall development on the inter- and 3.2) from 1996 to 2010 [3]. According to the Globocan Registry,
play between KC outcomes and its detection. The inverse asso- the cumulative risk of incidence averaged across different coun-
ciation between HDI and M/I ratio relates not only to variations tries worldwide varied from 0.21% at 50 years to 1.70% at 85 years
in healthcare quality and accessibility but also to region-specific from 1998 to 2012.
nuances in epidemiological data collection, the clinical manifes- Mortality trends are region-specific and varied over time. In
tation of the disease, and the effectiveness of available treatments Central and South America, mortality rates have been increasing,
for KC [5]. These aspects are explored in greater detail in the fol- especially in Brazil. In Northern and Western Europe, as well as
lowing sections, providing a more granular understanding of the in the USA, mortality began to decline in the 1990s. Conversely,
global KC landscape. in Southern Europe mortality rates have been on the rise. In most
of Asia, mortality trends have been more stable, with declines ap-
Temporal trends parent in Israel and Japan from the mid-1990s. For Africa, no sig-
Understanding temporal trends of incidence, prevalence and mor- nificant changes in mortality have been observed in the recent
tality of KC provide critical insights for the development of in- period. In Oceania, while the incidence has been increasing, mor-
formed public health strategies and future research initiatives. tality has been decreasing in Australia and remaining stable in
Delving into cancer trends over the years, KC incidence is rising New Zealand [2].
globally, with varied trends in mortality across regions influenced Notably, substantial regional differences and their fluctuation
by factors like diet, obesity and healthcare access. The incidence over time can be attributed to many factors, many of which are
is notably high in Western countries, linked to lifestyle risk fac- still under investigation and difficult to condense. As an example,
tors, while regional dietary patterns and economic disparities af- risk factors for KC such as obesity, hypertension and smoking (as
fect global variability. discussed later) are very prevalent in Western Countries [7]. Diet
922 | Nephrol Dial Transplant, 2024, Vol. 39, No. 6

A
12
Prevalence (male)
11
10

ASR (World) per 100,000

9
8
7
6 Prevalence (female)
5
4
Mortality (male)
3
2
1 Mortality (female)

94
96

98
00
02
04

06
08

10
12

14
19 Female

19

19
20
20
20

20
20

20
20

20
Year

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B C
300 2020 2040 2020 2040
248 200
200 59% Year 141 Year
163 100
new cases (thousands)

156 18% 76%

Estimated number of

Estimated number of
138

deaths (thousands)
80 80 71
100 98 60 31%
80 27% 54
77 40
60 58
50 30 28 25
40 62%
36
20 19 74% 48%
30 30 16 17
77%
72% 10 11
20
18 8
6
10 4
8 8
3 2.6
6 48%
5 5 2 67%
1.5
ia

ia
a

a
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ia

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ia
or bbe rica

or bbe rica
ric

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As

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Af

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C m

C m
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Figure 2: Panel A: worldwide prevalence (continuous) and mortality (dashed) ASR for males (blue) and females (red) from 1994 to 2014. Panel B:
estimated number of new cases in different continents from 2020 to 2040. Panel C: estimated number of new deaths in different continents from 2020
to 2040. Data from the Globocan 2020 [1].

modification experienced in recent years, leading to an increase global health challenge; more research and monitoring sys-
in general body mass index (BMI), can account for the additional tem is needed for KC to gain insights in main contributors of
variability observed in other countries, such as China [8]. Con- epidemiology.
versely, the plant-based diet of some parts of the world may result
in protection from KC, although definitive data are lacking [9, 10].
Access to screening through second-level imaging investigations, Socioeconomic and racial/ethnic disparities
as well as the access to the different and newer treatment estab- The global epidemiology of KC reveals significant disparities
lished for KC, usually less available in low-income countries or in across economic, social and racial lines. According to Globocan
specific population subgroups, are additional factors affecting es- 2020, countries with low or medium HDI are projected to wit-
timates’ variability [7]. Additionally, in regions such as Central and ness the most substantial relative increases in cancer incidence
Eastern Europe, where a higher uptrend of incidence has been reg- by 2040 [1, 13]. As previously mentioned, it is noteworthy that re-
istered, specific factors have been investigated. Notably, the high gions with higher HDI report elevated crude and ASR of KC in-
incidence of KC has been associated with occupational exposure, cidence and mortality (Fig. 2), along with lower M/I ratio, com-
especially in agriculture, a prevalent industry in some of these ar- pared with less developed regions [14]. Socioeconomic factors also
eas [11]. Finally, reporting and its accuracy, which can vary world- play a pivotal role in these disparities. Individuals residing in de-
wide, significantly affect epidemiology data. For instance, the US prived areas or belonging to lower education and income groups
“Surveillance, Epidemiology, and End Results Program” is gener- tend to have higher incidence and mortality rates. This pattern,
ally considered the gold-standard for data quality amongst can- observed across various cancers including KC, can be attributed
cer registries; China has improved its system in the last years; and to lifestyle factors, as well as differences in access to screening
in Europe, European Network of Cancer Registries does not cover and treatment services [15, 16]. These socioeconomic inequalities
the whole population, while registries in other countries are still have been widening over time, with mortality decline being slower
to be implemented [12]. in lower socioeconomic groups [17–19]. In addition, rural areas are
In conclusion, the ongoing rise in KC incidence in most characterized by higher incidence and mortality of different types
countries, alongside diverse and region-specific mortality trends, of cancer in comparison with urban ones in high income countries
underscores the importance of continuous monitoring and [20]. Of note, specific studies on KC are lacking, with only one re-
the development of targeted interventions to address this port from Austria [21].
 L. Cirillo et al. | 923

Non modifiable
risk factor
Genetic background
Risk of kidney cancer

Secondary
prevention

Surgery AKI/CKD
AKI/CKD Drugs Kidney diseases

Primary
prevention

Obesity Diabetes
t
tes Smoking Hypertension
Hype Work exposure

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Figure 3: Representation of KC risk factors and their relationship to KD. The diagram outlines various risk factors of KC, organized in a hierarchical
fashion based on the risk level they impose. The lower tier, indicating high prevalence but less risk, includes modifiable broad environmental and
lifestyle-associated factors. The middle tier, representing increased risk, encompasses kidney injury factors, mainly AKI and CKD. The upper tier points
to genomic determinants that carry the highest risk but affect a smaller population segment. The background color variations represent the potential
for interventions at different levels to reduce KC risk in different groups of population. This hierarchical understanding of risk factors is instrumental
in shaping the global epidemiology of KC and formulating targeted prevention strategies.

Racial disparities, while global, are evident within individual gories: genomic determinants and modifiable lifestyle-associated
countries also. For instance, in the USA the incidence of KC is risk factors [28–30] (Fig. 3).
significantly higher among Black than in Caucasian populations. Less than 5% of KC are explained by genetic predisposition,
Interestingly, the typical risk factors observed in Caucasians— which however confer the highest risk of developing the disease.
obesity, hypertension and cigarette smoking—seem not to have On the other hand, modifiable risk factors account for up to 40% of
the same influence in the Black population [22]. Access to care and increased risk, but are highly prevalent in the general population
additional comorbidities represent potential factors affecting sur- [31].
vival disparities between White and Black patients. Indeed, Black KC is significantly influenced by genetic predispositions, ne-
patients with KC often present a different comorbidities rate, are cessitating tailored medical interventions [29]. Key hereditary
younger and have a lower tumor stage. However, race does not in- syndromes like Von Hippel-Lindau (VHL) and hereditary leiomy-
dependently predict survival, suggesting that survival differences omatosis and RCC, although rare, elevate KC risk, with VHL pa-
in large registries may be due to healthcare access barriers and/or tients having a 25%–45% likelihood of developing renal tumors.
comorbidity rather than disease biology [23]. The hereditary papillary RCC and Birt-Hogg-Dubé syndrome are
Other racial and ethnic groups, such as Hispanic Americans also notable for their strong genetic linkage to KC through muta-
and Native Americans, also bear a disproportionate burden of KC tions in the MET and FLCN genes. In children, specific genetic syn-
compared with European Americans. Hispanic Americans have a dromes significantly raise the risk of nephroblastoma/WT. These
younger average age at diagnosis and nearly three times the odds genetic factors generally lead to an earlier onset and diagnosis of
of diagnosis by the age of 50 years. Native Americans also tend KC compared with non-genetic cases (reviewed in [32, 33]). This
to be diagnosed at a younger age. Clear-cell renal cell carcinoma is in line with observations in other hereditary cancer syndromes
(RCC), a subtype of KC, is more prevalent among these popula- (e.g. hereditary breast–ovarian cancer).
tions [15, 24, 25]. In these groups, the higher incidence of obesity To make the picture more complex, evidence suggests that
and chronic kidney disease (CKD), and language barrier, but not sex significantly influences the epidemiology of KC (reviewed in
insurance, are possible suggested major determinants of early di- [34]). Men are disproportionately affected, with a 2-fold greater
agnosis of KC [24]. risk of development and fatality from the disease compared with
These disparities underscore the need for a multifaceted ap- women. Biological differences in hormone signaling and gender-
proach in developing prevention and control strategies for KC. Al- related behaviors contribute to this disparity, impacting tumor
though preliminary interventions have been conducted in other characteristics and the efficacy of treatments. Recognizing these
settings, such as specific screening guideline for minorities for sex-based variances is critical for advancing targeted prevention
some cancer like breast cancer [26], the research in this field is and therapeutic strategies in KC care.
still limited and cancer health disparities remain a common is- Beside genetic determinants, modifiable lifestyle-associated
sue to many types of cancer [27]. risk factors have been reported in association with KC. They in-
clude environmental exposure to toxic compounds, smoking, obe-
sity and increased BMI [28, 30]. Notably, they are also linked to
RISK FACTORS OF KIDNEY CANCER: A kidney injury.
SHARED PATHWAY WITH KIDNEY INJURY The association between KC and environmental or occupa-
tional exposure has been described since the 1970s. In a 1995
Discerning risk factors of KC is vital for formulating early detec- international multicenter case–control study, exposure to toxic
tion methods, prevention strategies and directing future research. compounds such as cadmium, asbestos and petroleum byprod-
The predominant risk factors for KC fall into two primary cate- ucts were linked to an increased risk of KC [35]. Of note, the same
924 | Nephrol Dial Transplant, 2024, Vol. 39, No. 6

authors described a negative association between KC and educa- in preventing KC [50]. Significantly, childhood cancer survivors
tion, suggesting that a low-level of education lead to high occupa- exhibit an elevated risk of developing KC, especially when their
tional risk (blast-furnace workers, coke-oven industry, steel and treatment regimen involved nephrotoxic agents like cisplatin
iron industry). or kidney-directed radiotherapy, often leading to AKI during
Chronic ingestion or abuse of nonsteroidal anti-inflammatory treatment [57]. Accordingly, the therapies commonly used for KC,
drugs, often used over the counter for pain relief, is reported to kidney surgery and chemotherapeutics can themselves cause AKI
increase the risk of KC [36]. and CKD, which further complicates the relationship between
As for smoking, approximately 18%–30% of KC cases are at- KC and KD [58]. In support of these observations, recent studies
tributed to tobacco exposure, with the risk of KC being 1.36-fold supported an increased risk of KC in patients with gallstones [59],
higher in current smokers compared with never smokers [37]. which are likely to result from the interaction of a spectrum of
Notably, there is a dose–response relationship between smok- environmental and genetic risk factors associated with chronic
ing intensity, duration and time since quitting, with the risk of overnutrition with carbohydrates, depletion of dietary fiber, age,
KC. Heavy smokers have worse outcomes than light smokers or female sex, type 2 DM, obesity and low physical inactivity [60]. Of
never/former smokers, indicating that smoking habits also impact note, cholelithiasis shares risk factors with CKD and KD, strongly
post-diagnosis prognosis [38, 39]. suggesting a common underlying mechanism.
Globocan data show that 13.4% of overall KC cases are at- An interesting aspect that reinforces the interrelationship be-

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tributable to elevated BMI [1, 40, 41]. Interestingly, despite increas- tween KD and cancer is the increased risk of medullary carcino-
ing the incidence of KC, obesity may confer a protective effect in mas, in patients with recurrent AKI [50]. Sickle cell disease pa-
terms of survival after diagnosis. However, this complex relation- tients or patients with a sickle cell trait are prone to suffer AKI,
ship, often termed the “obesity paradox,” is not completely under- subsequent CKD/ESKD, and peculiarly medullary carcinoma. In-
stood, and further research is needed [42]. Interrelated conditions terestingly, a retrospective study showed that high intensity phys-
like insulin resistance, diabetes mellitus (DM) and dyslipidemia ical exercise, which usually reduces the risk of KC [61], aggravates
often coexist in obese or overweight patients (i.e. metabolic syn- renal hypoxia in the setting of sickle cell disease increasing the
drome). The link between DM and KC is particularly significant in risk of this specific carcinoma [62]. The role of AKI in promot-
females [43]. However, the precise impact of DM on patients with ing KC, especially papillary renal cell carcinoma which is more
KC remains inconclusive, with some studies suggesting a nega- frequent in the CKD/ESKD population, was evaluated in a recent
tive influence, while others report no association [28]. In contrast, study of lineage tracing of tubular epithelial cells after AKI in-
there is evidence of a decreased risk of KC associated with met- duction and long-term follow-up in mice showed time-dependent
formin, a drug that enhances insulin sensitivity, indicating a po- onset of clonal papillary tumors in an adenoma–carcinoma se-
tential therapeutic angle [44]. quence [56]. This suggests for the first time a mechanistic link be-
Hypertension demonstrates a stronger association with KC in- tween reiterating KD and cancerogenesis. As a central paradigm,
cidence, leading to a 10-fold increase in risk [45, 46]. The risk of the mechanisms of kidney damage and repair that are active dur-
KC increases with the severity of hypertension and the need for ing AKI, but also during persistent injuries in CKD, act also as trig-
multiple therapies, following a dose-dependent pattern [47]. Each gers of DNA damage, promoting the expansion of (pre-)malignant
10-mmHg increase in blood pressure correlates with an additional cell clones [50].
10%–22% increase in KC risk [48].
Cumulation of several risk factors for KC is not infrequent. The
2004–10 Centers for Disease Control and Prevention report esti- THE ROLE OF NEPHROLOGIST IN KIDNEY
mated that the annual average prevalence of smoking was higher CARE
among the population with occupations associated with high risk As previously mentioned, epidemiological studies have identified
for KC, as mining industry, construction and extraction occupa- many risk factors that are shared between AKI and/or CKD and
tions, in comparison with the general adult population (30% vs KC [63, 64]. In this context, managing such risk factors in the gen-
19.3%) [49]. eral and CKD population makes the nephrologist central in pri-
The pathogenic link between these modifiable risk factors and mary prevention of KC. Indeed, imaging techniques can reveal a
cancerogenesis is not fully elucidated. One explanation could be 4%–14% incidence of KC in dialysis patients. However, universal
that they promote kidney injury by imposing adaptive mecha- screening of dialysis patients, although strongly suggested before,
nisms to sustain metabolic needs [50]. In fact, toxic compounds is still a matter of debate [65]. Moreover, pre-existing CKD, protein-
can induce episodes of toxic acute kidney injury (AKI) associated uria and episodes of AKI can complicate management and prog-
with necroinflammation and oxidative stress, while obesity, di- nosis of other cancers [66, 67].
abetes and smoking can lead to glomerular hyperfiltration and CKD and AKI are recognized complications of many types of
glomerulosclerosis-related CKD. Smoke has multiple effects as it cancer and their therapy also [68]. Risk factors for CKD may be
could also induce genetic alteration involved in KC [51]. patient-specific, cancer-specific or cancer therapy–specific [50, 69].
AKI, CKD and end-stage kidney disease (ESKD) have a strong The development of AKI is an important and often overlooked eti-
correlation with a high incidence of KC [52–54]. Patients with ology for CKD among patients with cancer. Patients with severe
ESKD have a 2- to 10-fold increased risk of developing KC, with AKI who require dialysis and who recover are at high risk of pro-
ESKD heightening also the risk of mortality [52, 55]. Notably, gression to CKD and the severity of AKI is a strong predictor of
KC is more frequently observed in native kidneys than in grafts progression to CKD [68].
[54]. These findings suggest that immune system impairment CKD is a common complication in patients receiving anti-
due to CKD or immunosuppressive therapy alone cannot ac- neoplastic nephrotoxic drugs used to treat KC itself [68, 70, 71].
count for the increased risk of KC [56]. This complex interplay For example, most patients treated with platinum compounds
between AKI, CKD and KC suggests a continuum, emphasizing frequently experience a small but permanent decline in esti-
the importance of preventing AKI, particularly in populations mated glomerular filtration rate [72]. Similar outcome has been
who are already at high risk of CKD and KC, as a key factor reported for tyrosine kinase inhibitors (TKIs) [73]. Drugs targeting
 L. Cirillo et al. | 925

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de

Figure 4: The central role of nephrologists in the epidemiology and management of KC. This diagram illustrates the multifaceted involvement of
nephrologists in managing KC. The core represents the nephrologist’s role in early detection, prevention, treatment of CKD and AKI, and management
of KC. The outer circle enumerates key risk factors for CKD and subsequently KC. This highlights the nephrologist’s crucial role in understanding,
mitigating and managing these risk factors, ultimately influencing the global epidemiology of KC.

the vascular endothelial growth factor pathway can lead to a prevalence. The interplay between KD and KC brings a new per-
wide range of glomerulopathies, such as thrombotic microan- spective on prevention strategies. The rising incidence of KC, cou-
giopathy or focal segmental glomerulosclerosis [70, 71]. Newer pled with projected growth, necessitates a medical priority shift,
immunotherapies like PD-1 and CTLA-4 inhibitors can be respon- especially with the amplified disparities in low to medium HDI
sible for immune-related adverse events such development of countries. The pivotal role of nephrologists emerges in this nar-
autoimmunity, AKI and tubulointerstitial nephritis, from weeks rative, their expertise potentially fostering a more comprehensive
to months after exposure [68, 74]. disease understanding and improved patient outcomes. Future re-
Moreover, nephrologists are central in the management of con- search should focus on unraveling the kidney health and KC rela-
comitant electrolyte complications [68]. Targeted cancer therapies tionship, with an emphasis on longitudinal studies, addressing so-
increase the occurrence of hypertension with a relative risk of 3- cial disparities and incorporating multi-disciplinary approaches.
to 7-fold, with a cumulative incidence between 17% and 80% [68, The evolution of our understanding should guide our approach to
75]. combating this global health challenge, thus translating insights
Invasive surgical procedures for the management of KC also into improved patient outcomes.
pose a risk factor for the development of CKD. Postoperative AKI
after radical nephrectomy is associated with a greater than 4-
fold higher risk of developing new-onset CKD. On the other hand, ACKNOWLEDGEMENTS
nephron-sparing partial nephrectomies are associated with im-
L.C. and F.B. are members of ERKNet.
proved outcomes with less postoperative AKI and CKD [76, 77].
To this regard, few studies assessed the pathology of the non-
neoplastic portion of the kidney removed for KC to give prognostic
information on clinical management of these patients [78]. AUTHORS’ CONTRIBUTIONS
In conclusion, the role of the nephrologist in the management L.C. and F.B. conceived of the presented idea; L.C. and S.I. extracted
of patients with KC is crucial, not only during the screening and the data; L.C. and S.I. wrote the manuscript; F.B. supervised and
treatment of the cancer itself but also in the prevention and man- revised the paper.
agement of CKD and AKI, which are common complications of
cancer and its therapy. It also highlights the importance of multi-
disciplinary collaboration in the management of KC, with nephrol- DATA AVAILABILITY STATEMENT
ogists playing a central role not only in diagnosis and treatment,
but also in prevention of this disease. A collaborative approach to The data reported by this study are available in The Global Cancer
KC care will hopefully improve patient outcomes. Observatory (GCO) website at [Link] (reference [1]).
These data were made available by the International Agency for
Research on Cancer.
FUTURE PERSPECTIVES AND RESEARCH
DIRECTIONS
KC epidemiology presents a complex mosaic of geographical, tem-
CONFLICT OF INTEREST STATEMENT
poral and sociodemographic determinants, alongside a growing None.
926 | Nephrol Dial Transplant, 2024, Vol. 39, No. 6

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Received: August 4, 2023; Editorial decision: January 16, 2024

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