REVIEW

Caffeine and the Kidney: What Evidence

Right Now?
Davide Bolignano, MD, Giuseppe Coppolino, MD, Antonio Barillà, MD,
Susanna Campo, MD, Manila Criseo, MD, Donatella Tripodo, MD,
and Michele Buemi, MD

Caffeine, or 1, 3, 7-trimethylxanthine, is one of the most frequently consumed active drugs worldwide. Its main
mechanisms of action include inhibiting the phosphodiesteratic enzyme and adenosine receptors and activating the
ryanodine receptors with several actions on all organs. What effect does caffeine have on the kidney? Is caffeine
beneficial or dangerous? A review of the current literature reveals conflicting opinions regarding the prolithiasic
effect of this substance, whereas its diuretic action is least disputed and more easily observed. Caffeine may have
a toxic or preventive effect in some physiologic or pathologic conditions. Some of these incongruences may
depend on several factors, such as dosage, prior chronic exposure, genetic– enzymatic axes, and concomitant
drug consumption. While awaiting further insight from forthcoming studies on the issue, we may reach a preliminary
conclusion that, as yet, there is no evidence contraindicating the consumption of the equivalent of 3 to 4 cups
of coffee per day in healthy or nephropathic subjects. However, particular attention should be paid to the elderly,
children, and patients on concomitant treatment with analgesics or diuretics, whereas in subjects with a family or
clinical history of calcium lithiasis a moderate caffeine consumption should be associated with an adequate fluid
intake. Further in-depth studies are required to investigate whether this beverage is beneficial to patients on
hemodialysis.
© 2007 by the National Kidney Foundation, Inc.

I T HAS NOW BECOME A well-established

habit in the West to start the day with a cup
of coffee, and many believe that this drink, in-
vented by the Arabs, is the most frequently con-
sumed beverage worldwide. It has a unique flavor
and numerous positive effects on the organism,
but the risk of abuse is around the corner. Some
people, prompted by the need to maintain high
levels in the bloodstream to maximize their at-
tention and stay awake or to take advantage of its
psychostimulatory effects, become chronic con-
sumers of caffeine. This situation has led physi-
cians in general and nephrologists in particular to
question its value and examine its real risks. From
From the Department of Internal Medicine, University of
Messina, Messina, Italy.
Address reprint requests to Michele Buemi, MD, Via Salita Villa
Contino, 30, 98100 Messina, Italy. E-mail: buemim@unime.it.
© 2007 by the National Kidney Foundation, Inc.
1051-2276/07/1704-0001$32.00/0
doi:10.1053/j.jrn.2007.02.006
a clinical standpoint, caffeine, or 1, 3, 7-trimeth-
ylxanthine, belongs to the family of alcaloids and
the methylxanthine group. It is present in tea-,
coffee-, cocoa-, and chocolate-based beverages,
and is contained in several soft drinks and a
variety of drugs (above all, analgesics) as an adju-
vant and a psychostimulant. The standard values
for the caffeine content in different food products
and drinks are now strictly regulated.1 The me-
dium-size cup (150 mL) of roasted coffee con-
tains approximately 85 mg of caffeine, a cup of
instant coffee contains 60 mg, a cup of decaffein-
ated coffee contains 5 mg, brewed tea contains 30
mg, soluble tea contains 20 mg, and a cup of hot
chocolate contains approximately 4 mg (Table 1).
Caffeine is rapidly absorbed in the gastrointestinal
tract; complete absorption occurs 45 minutes af-
ter ingestion, and the plasma concentration peak
is reached 15 to 120 minutes after its consump-
tion. The consumption of 5 to 8 mg of caffeine
per kilogram of weight triggers a plasma concen-

Journal of Renal Nutrition, Vol 17, No 4 ( July), 2007: pp 225–234 225

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226 BOLIGNANO ET AL

Table 1. Caffeine Content in Common Food of transduction of the signal based on IP3 and
Caffeine c-AMP as second messengers.4,5
Product Size Content (mg) The most important studies in literature on
caffeine once focused on evaluating its effects on
Caffeine tablet 1 tablet 200
Coffee, roasted 150 mL 85
the central nervous system and the cardiocircula-
Coffee, instant 150 mL 60 tory apparatus in relation to, above all, its psycho-
Coffee, decaffeinated 240 mL 5 and physiostimulatory characteristics (Table 2).
Coffee, expresso 57 mL 100 Any attention to the response of the kidney to
Chocolate, dark 1 bar (43 g) 31 caffeine was initially limited to studies on varia-
Chocolate, milk 1 bar (43 g) 10
Hot chocolate, cup 150 mL 4
tions in the renal blood flow6 and the enhance-
Soft drink, Cola Classic 355 mL 34 ment of toxicity from analgesics.7,8 The subse-
Tea, green 240 mL 15 quent improvement in research on xanthine
Tea, leaf or bag 240 mL 30 receptors prompted a renewed interest in the
numerous renal functions that change in response
tration of approximately 8 to 10 mg/L. The to exposure to caffeine.
half-life of caffeine in plasma is 2.5 to 4.5 hours in
young subjects and slightly longer in elderly sub-
jects.2 Caffeine metabolism is species-specific. In Caffeine and Diuresis: Is There
humans, approximately 80% of caffeine is de- Any Evidence?
methylated to paraxanthine and approximately It is well known that caffeine has a diuretic
16% is converted into theobromine and theoph- effect. Findings from various studies are in agree-
ylline in the liver (Fig. 1). Approximately 3% of ment on this issue, demonstrating that in healthy
caffeine ingested and more than a dozen of its volunteers the acute administration of caffeine, or
metabolites can be found in urine. Various mech- drinks containing it, causes a short-term increase
anisms have been proposed to explain the effects in diuresis and the excretion of substances such as
of caffeine: increased release of intracellular cal- sodium, potassium, chlorides, magnesium, and
cium and inhibition of phosphodiesterases en- calcium.9,10 After the oral or endovenous admin-
zymes that hydrolyze c-AMP, resulting in an istration of 5 mg/kg of caffeine, a positive corre-
overall intracellular increase in this second mes- lation is observed between the subsequent 24-
senger.3 It is widely agreed that physiologic con- hour urinary flow and the clearance of the same
centrations of caffeine (⬃100 ␮M) or other substance in young and elderly healthy volun-
methylxanthines also act by antagonizing the ef- teers.11 This correlation appears even stronger in
fects of adenosine through competitive interac- elderly subjects after the endovenous administra-
tions with adenosinic receptors A1, A2, A3, and tion of 4 mg/kg of caffeine.12 A more recent
A4, which are linked with protein G and systems study demonstrated that the oral administration of

Figure 1. Chemical struc-

ture and methabolism of
caffeine (1, 3, 7-trimethyl-
xanthine).

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 CAFFEINE AND THE KIDNEY 227

Table 2. Main Extrarenal Actions of Caffeine

System Effect(s)

Central nervous system
Cardiovascular system
Gastrointestinal system
Respiratory system
Metabolism
Stimulatory effect on the cortex, respiratory, vasomotor, and vagus centers; peripheral
hyperreflexia, increase of psychomotor performance and fatigue resistance, pro-
awake effect
Increase in blood pressure, plasma renin activity, and heart rate (risk of development
of arrhythmias), vasoconstriction/vasodilation
Increased stomach acid secretion and peristalsis (at high doses), decreased pressure
in the lower esophageal sphincter
Bronchodilation
Increased release of stress hormones (cortisol, epinephrine, and norepinephrine),
glucose (hyperglycemia), cholesterol, and homocysteine; insulin resistance,
aggravation of hypoglycemia; increase in basal metabolism

a single dose of 15 mg/kg of caffeine in 13 caffeine (corresponding to approximately 10 cups

preterm newborns caused an increase in both
urinary flow and creatinine clearance in two
consecutive periods of 12 hours of observation.13
Some studies seem to contradict these obser-
vations. Grandjean14 found no substantial differ-
ence in the hydric state of healthy volunteers who
consumed beverages, some of which contained
caffeine, whereas another subsequent study evi-
denced that the administration of 6 mg/kg of
caffeine for 4 days in healthy volunteers, after a
previous phase of equilibration of 1 week, did not
cause important variations in the body mass, uri-
nary osmolarity, specific weight of urine, volume
of urine, and natriuresis in the subsequent 24
hours, creatininemia, plasma osmolarity, hemat-
ocrit, and plasma proteins.15 It is likely that in
subjects with previous chronic consumption, the
diuretic effect of a dose of caffeine would be
reduced. As previously found in elderly subjects
used to consuming a moderate and constant
amount of caffeine, the cardiovascular effects of a
single oral load were significantly milder than in
subjects without previous exposure.16
Other authors have considered another funda-
mental parameter, the doses of caffeine ingested,
in evaluating whether it has a diuretic effect.
Passmore et al.17 used increasing doses of caffeine
(from 45, 90, 180, to 360 mg) and found that
only quantities not less than 360 mg caused sig-
nificant increases in the urinary flow, whereas 90
mg was enough to significantly increase natriure-
sis. In a recent review, a systematic analysis was
made of the various evidence in the literature on
the topic, and it was concluded that acute in-
creases in diuresis can occur after the administra-
tion of at least 300 mg of caffeine.18 In addition,
reduced body water after a dose of 642 mg of
of coffee) has been confirmed in studies using
bioelectrical impedance analysis.19
It has been suggested that the diuretic effect of
caffeine may be mediated by an increased release
of catecholamines into the circulation and by an
increase in their peripheral inhibition of phos-
phodiesterase.20 This hypothesis was partly con-
firmed in a subsequent study that demonstrated
that the increase in diuresis caused by the con-
sumption of beverages containing caffeine was
significantly greater in cases of an increased sys-
temic release during prolonged physical exercise
than in a condition of rest.21 One recent study on
mice provided important evidence furthering our
understanding of the diuretic action of caffeine.
In knockout mice for the receptor gene A1, Rieg
et al.22 demonstrated that the administration of
caffeine or theophylline had no effect on diuresis,
whereas it did determine a marked increase in
controls. However, the diuretic effect of caffeine
is also partly linked to its natriuretic action. Find-
ings in a recent study showed that the caffeine-
induced increase in sodium excretion, previously
described by several other authors, is partly linked
to a reduction in proximal and distal tubular of its
fractional absorbance.23 This mechanism appears,
moreover, to be independent of the action of
natriuretic atrial peptide, in which no significant
plasma variations were observed 2 hours after the
administration of 250 mg of caffeine in healthy
subjects, whereas after 1 hour there was a signif-
icant increase in diuresis, the excretion of sodium
and potassium, and urinary osmolarity.24 How-
ever, in a recent study on mice, other authors
described a completely different response on ad-
ministering caffeine in oral boluses, followed by
water supplementation. In the short term, an

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228 BOLIGNANO ET AL

Table 3. Main Studies About Caffeine and Lithiasis

Authors Year Patients Results Characteristics

Shuster et al.33 1985 2295 (men) Negative association between Old population study. No
coffee consumption and important data, e.g., about
stone disease in white male fluid intake.
patients.
Bergman et al.27 1990 37 (women) Increase in urinary Ca excretion Evaluation of only acute
and decrease in Ca effects after caffeine
reabsorption after oral administration. No data on
introduction of caffeinated long-term effects.
beverage (6 mg/kg caffeine).
Zanardo et al.28 1995 20 Increase in urine Ca-excretion Caffeine treatment and effects
(10- to 15-fold) in premature observation prolonged to
neonates treated with caffeine 5 d. High doses
e.v. (loading dose 10 mg/kg, administered (intravenously).
maintenance dose 2.5 mg/kg/
12 h for 5 d).
Curhan et al.34 1996 45,289 (men) Risk of stones decreased by Prospective study generally
10% after daily consumption well conducted. Very wide
of 240 mL of coffee and by population.
14% after 240 mL of tea.
Curhan et al.35 1998 81,093 (women) Risk of stones decreased by Prospective study generally
10% after daily consumption well conducted. Very wide
of 240 mL of coffee and by population.
8% after 240 mL of tea.
Massey and Sutton26 2004 39 Increase in urinary Ca/creatinine Experimental study. Evaluation
but not oxalate/creatinine 2 h of only acute effects after
after oral introduction of caffeine administration. No
caffeine (6 mg/kg) in data on long-term effects.
normocalcemic subjects after
14 h of fasting.
Ca, calcium.

increase was observed in the mRNA expression
of atrial natriuretic peptide and its circulating
levels and the enhancement of nitric oxide syn-
thetase endothelial isoform expression.
It was demonstrated that caffeine induces a re-
duction in the expression of the Na⫹/K⫹ adeno-
sine triphosphatase pump and isoform 3 of the
Na⫹/H⫹ exchange; both are key proteins in the
mechanism of active/passive tubular reabsorp-
tion.25 On consideration of the experiment con-
ducted by Rieg et al.,22 and the fact that A1R -/-
mice were not responsive even to the natriuretic
effect of xanthines, it seems possible that the
above-cited mechanisms might depend in part on
the inhibitory effect of caffeine in the presence of
the adenosinic receptors A1, whose stimulation
would reduce natriuresis and diuresis.
Caffeine and Renal Lithiasis: For
or Against?
Coffee is often included in the list of food
products prohibited or restricted in subjects with
a history of recurrent renal colic who are referred
to a specialist for an appropriate diet. Does caf-
feine really have a prolithiasic effect? Findings in
the literature are conflicting (Table 3).
In 2004, Massey and Sutton26 demonstrated
that caffeine consumption at a dose of 6 mg/kg of
lean mass after 14 hours of fasting in 39 volunteers
caused an increase in the excretion of calcium,
magnesium, and citrate, with an increase in the
Tiselius index for calcium oxalate stones forma-
tion from 2.4 to 3.1 in subjects with a history of
calcium lithiasis and from 1.7 to 2.5 in subjects
without this history. Overall, the consumption of
coffee seemed to increase, albeit modestly, the
risk of forming calcium oxalate stones. Findings
in another less recent study demonstrated that the
administration of caffeine in healthy young
women caused an increased urinary loss of cal-
cium and magnesium, with a significant reduc-
tion in the reabsorption percentage after its con-
sumption (P ⬍ .001 and P ⬍ .0001 for calcium
and magnesium, respectively), whereas other pa-

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 CAFFEINE AND THE KIDNEY
rameters, such as creatinine clearance, were not
modified.27 Another independent study that con-
firms the above findings was conducted in Italy
on preterm newborns. Most of these patients
underwent long-term methylxanthine therapy
for respiratory distress and apnea, and the most
frequent side effects of this therapy were nephro-
calcinosis and osteopenia. The authors demon-
strated a significant increase in the urinary excre-
tion of calcium, calcium/creatinine, and calcium/
sodium in the newborns treated with theophylline
and caffeine with respect to the preterm, non-
treated controls. This probably contributed to
determining the iatrogenous complications.28 It
was recently suggested that caffeine not only
increases the risk of calcium lithiasis but also plays
a role in uric lithiasis. A typical case of aggressive
recurrent renal acid 1-methyluric calculosis in a
white patient who habitually drank at least eight
cups of coffee per day was described. In this case,
a high percentage of calcium oxalate stones was
also found in the patient’s urinary sediment.29
Overall, the findings reported in these studies are
in agreement that hypercalciuria could be the
main pathogenic factor causing caffeine to trigger
the formation of kidney stones.
The exact mechanism underlying increased
calcium loss is as yet unclear and is still the object
of more in-depth studies. McPhee and Whiting30
demonstrated that the hypercalciuric effect of
caffeine may in part be limited by the adminis-
tration of adenosine receptor agonists and sug-
gested that the main mechanism underlying this
phenomenon is the blockage of these receptors.
This hypothesis was also confirmed by Massey
and Whiting31 The recent discovery that caffeine
also acts as an agonist of the ryanodine receptors
(involved in calcium release) suggests that the
latter mechanism plays a more important role. A
Chinese group demonstrated that caffeine triggers
an increased release of calcium ions by interacting
with these receptors in embryonic renal cells.32
In contrast, data from epidemiologic studies
prove that caffeine, paradoxically, may have a
protective effect against lithiasis.
A well-known case-control study demon-
strated an inverse association between the mod-
erate consumption of coffee and a history of
kidney stones.33 In a subsequent study conducted
in the United States on a cohort of 45,289 men,
753 new cases of kidney stones were diagnosed,
but the risk of developing stones decreased by
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229
10% in response to daily consumption of 240 mL
of coffee.34 For a period of approximately 2 years,
the same authors studied a cohort of 81,093
women and made 719 new diagnoses of kidney
stones; the risk of developing stones decreased by
10% in response to 240 mL/day of coffee and by
8% in response to 240 mL/day of tea.35
With the use of multivariate models, these
results were “adjusted” simultaneously for several
beverages and other risk factors, thus excluding
the possible influence of other substances.
A possible explication of this apparent contra-
diction could be linked to the diuretic properties
of caffeine because chronic consumption of this
substance can promote not only calcium excre-
tion but also diuresis and natriuresis. It is well
known that an increase in urinary flow, if ade-
quately compensated by water introduction, rep-
resents an important factor against every type of
lithiasis through prevention of stone formation.36
Constitutional and genetic factors, pathologic
conditions, and concomitant drug consumption
may also play a significant role.37
Caffeine and the Kidney: Toxicity
or Protection?
Numerous studies have shown how caffeine
has other types of toxic effects on the kidney. A
massive load of coffee through the oral route (in
the literature, amounts of up to 50 g have been
described), taken, for example, to commit suicide
or as a consequence of a psychiatric disorder, soon
causes severe rhabdomyolysis with acute renal fail-
ure.38,39 The frequent finding of hyponatriemia
concomitant to hypernatriuria, somewhat unex-
pected in organic renal insufficiency, is explained
on considering the natriuretic effect of caffeine,
already well defined in studies by several authors.
In view of the severity of this clinical picture,
peritoneal dialysis or hemodialysis treatment may
often be indicated.40,41
In recent literature, an increasing number of
studies have demonstrated that chronic caffeine
consumption contributes to the development and
exacerbation of various kidney diseases. In two
interesting articles, Belibi et al.42,43 describe how
caffeine is to all effects a risk factor in the exac-
erbation of cysts in patients with autosomic dom-
inant polycystic kidney. The mechanism under-
lying this enhanced development seems to be
linked to an increase in intracellular c-AMP lev-
230
els, triggering the proliferation and accumulation
of fluid in the tubular cells. Increased intracellular
concentrations of this second messenger seem to
be linked partly to the inhibitory effect of caffeine
on the phosphodiesteratic enzyme and partly to
its effect on adenosinic receptors. In a previous
study it was found that the chronic administration
of small quantities of caffeine caused the early
onset, or exacerbation, of hypertension linked to
disease in mice with autosomic dominant poly-
cystic kidney, but not in diseased rats treated with
a placebo. In this study, however, no significant
variations in the glomerular filtration rate and cyst
dimensions were found at 6 months of chronic
administration.44 Another experimental model of
renal toxicity from chronic caffeine consumption
was reported by Tofovic et al.45 in their study on
rats as genetic models of the metabolic syndrome
after a short and long cycle of treatment with
caffeine. Although, positive effects were ob-
served, such as reduced body weight and glyco-
suria and improved glycidic tolerance, there was a
significant increase in proteinuria, an increase in
renal vascular resistance, and a reduction in the
inulin clearance, leading to marked renal failure.
Underlying this there was a marked worsening in
the histopathologic picture, with the develop-
ment of tubulointerstitial damage and a worsen-
ing in focal glomerulosclerosis.
Deterioration in renal function with an exac-
erbation of proteinuria has already been demon-
strated, again by Tofovic et al.,46 in rats with an
induced nephrotic syndrome after treatment with
puromicine-aminonucleoside, pretreated with caf-
feine. Also in this case, more severe histopatho-
logic alterations developed at the tubulointersti-
tial and glomerular levels, with a significant
reduction in the inulin clearance with respect to
the nontreated controls. The simultaneous find-
ing of a marked increased in the renin-plasma
activity suggested that the above effects may have
depended in part on an increased renin-angioten-
sin system activity. These effects are in clear
contrast with those of pentoxifylline, another
xanthine-derivate whose molecular structure and
mechanism of action are similar to that of caf-
feine.47 Unlike caffeine, pentoxifylline can in-
duce a significant reduction in microalbuminuria
and proteinuria in several diseases, including
membranous glomerulonephritis and the ne-
phritic syndrome secondary to lupus nephritis.48
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BOLIGNANO ET AL
This reduction, which appears similar to that
obtained after the administration of an angioten-
sin-converting enzyme inhibitor, captopril, in di-
abetic patients without hypertension and with an
intact renal function,49 in the same category of
patients further potentiates the antiproteinuric
effect of another category of drugs, the so-called
angiotensin II receptor blockers.50 Further in-
depth studies are required to clarify why caffeine
and pentoxifylline, which belong to the same
chemical family and have the same receptor tar-
gets and identical systemic effects, play such a
different role in this context.
Another frequently described adverse effect of
caffeine on the kidney depends on its ability to
potentiate the toxicity of analgesics. Several stud-
ies have focused on this aspect,51 and recently a
renewed interest has been expressed in this theme
in the attempt to definitively establish whether
the chronic consumption of analgesics associated
with caffeine may cause renal damage. The ratio-
nale for this drug association is based on the
adjuvant effect that caffeine has on the action of
the analgesic, allowing a reduction in the quantity
of analgesic needed to obtain the desired effect.
Laska et al.52 demonstrated that by associating
caffeine with paracetamol, a drug dose reduction
of 40% is achieved while obtaining the same
analgesic effect. In their recent study, Cai et al.53
showed how damage induced by drugs such as
acetaminophen and acetylsalicylic acid were en-
hanced if simultanously associated with caffeine.
This effect was achieved particularly in the cells of
the collector duct of the internal medulla, the
kidney region exposed to a greater osmolarity,
through the accentuation of the proliferation and
apoptosis from damage to DNA in normally
quiescent cells.
One possible mechanism underlying this injury
was subsequently proposed by Rengelshausen et
al., who demonstrated that the administration of
caffeine inhibited this protein in cell cultures with
overexpression of the trasportator-1 of organic
anions (involved in the excretion of various drugs
including anti-inflammatories)54 by determining
the accumulation of substances (e.g., carboxy-
fluorescein) caused by a reduction of their up-
take.55 However, other observational studies tend
to minimize the potential role of caffeine in the
toxicity of analgesics. If different case-control
studies have undeniably demonstrated that the
consumption of analgesics containing caffeine
 CAFFEINE AND THE KIDNEY
is associated with a higher incidence of ne-
phropathy, none of the studies have clearly
established that nephropathy is linked to the
exacerbation of damage from analgesics rather
than a direct effect of caffeine itself. There is no
evidence that caffeine promotes, through tol-
erance and dependency effects, a stimulus to
introduce a greater quantity of analgesics with
the consequent risk of renal damage from an
overdose.56,57 In complete opposition to all the
above-described effects of renal toxicity, nu-
merous authors have recently pointed out that
in particular conditions, as yet limited to ex-
perimental animal or cell models, caffeine can
have a protective effect on renal function. For
example, caffeine has an antagonistic effect on
adenosine receptors, and this may contribute to
the prevention of renal damage from ischemia
through an increase in diuresis, natriuresis, and
blood flow, which is reduced by the increase in
the resistance triggered by angiotensin and
adenosine.58 A comparable result was previ-
ously described in models of brain ischemia in
mice. The administration of caffeine or pen-
toxifylline 60 minutes before closing the ca-
rotid of anesthetized rats induced a higher
resistance to ischemic stress than that found in
controls, thus suggesting the possible applica-
tion of this concept to the prevention of dam-
age from ischemia, not only in experimental
animals but also in humans.59
Although the above model did not provide
definite molecular explanations for the isch-
emia-protective phenomena of xanthines, a
likely hypothesis is that it is involved in recep-
torial adenosine antagonism: Findings from
other studies have demonstrated how the same
mechanism underlies the protection from
nephrotoxicity by tacrolimus. In a well-known
series of studies it was shown how the pread-
ministration of teophylline prevented acute
damage from tacrolimus, probably caused by
adenosine through a vasoconstrictive effect
with a reduction in the blood flow and glo-
merular filtration rate.60,61 In another recent
work62 it was demonstrated that this effect is
achieved in particular through a specific A3
receptor blockade, by using selective antago-
nists of the various subclasses of adenosine renal
receptors. It was demonstrated that pretreat-
ment with three different xanthines (theophyl-
line, pentoxifylline, and caffeine) had a protec-
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231
tive effect toward glomerular contraction
induced by cyclosporine-A in mesangial cell
cultures.63 Finally, there are concrete experi-
mental bases for the rational explanation of the
protective effects of caffeine in human models.
Caffeine and Renal Failure:
What Risk?
Studies on the effects of caffeine in subjects
with nephropathy or chronic renal failure, and
in those on dialysis, are scarce, and it is hoped
that this aspect will be more satisfactorily in-
vestigated in the future. As previously ob-
served, the risk of caffeine exacerbating renal
disease or chronic renal failure has only been
investigated in animal models and cellular stud-
ies, and findings have not yet been confirmed
in humans. To our knowledge, it has not been
proven that chronic renal failure in itself incurs
a risk of slowing down the metabolism of this
substance with a consequent accumulation and
damage, as happens with other substances, such
as erythromycin.64
However, following their observations of its
administration during hemodialysis, some au-
thors have also pointed out that it may be
possible to exploit caffeine consumption. Stud-
ies on patient populations have shown that the
consumption of caffeine during dialysis might
become a useful semipharmacologic option for
the prevention and treatment of symptomatic
intradialytic hypotension.65,66 Moreover, it is
now widely agreed that chronic caffeine con-
sumption does not contribute to the restless leg
syndrome (RLS), one of the most frequently
observed disturbances of patients on hemodialy-
sis. In a recent study in northeast Italy, question-
naires were administered to a large population of
patients on dialysis with sleep disturbance patterns
in RLS; no significant differences were found
between the incidence of this syndrome in sub-
jects who did and did not habitually drink cof-
fee.67 A Chinese group observed that coffee con-
sumption did not play an important role in
contributing to RLS in patients who were on an
ambulatory regimen of continuous peritoneal di-
alysis.68 In conclusion, no sound findings have
been reported in the literature to justify contra-
indicating the consumption of moderate quanti-
ties of coffee, even in subjects with chronic renal
232
failure or those with terminal uremia on hemo-
dialysis or peritoneal dialysis.
Conclusions
As can be seen, a review of the current litera-
ture reveals conflicting opinions regarding the
extremes of the diuretic, prolithiasic, and toxic
effects of caffeine. The extreme variability of sub-
jective responses to the same molecule is partly
linked to the differences in the conditions used in
various experiments, dosages given, modality and
times of administration, basal state, genetic– enzy-
matic and metabolic axes, possible concomitant
pathologic conditions, and so forth.69,70 Underlying
the extreme interindividual variability linked to
modifiable and nonmodifiable factors (e.g., age,
gender, race, and body mass index) are the state of
addiction/tolerance and all that can generally in-
fluence the metabolism, kinetics, and dynamics of
almost any molecule with a marked pharmaco-
logic activity, such as caffeine.
Is caffeine good or bad for the kidney? Overall,
we found no evidence in the literature that the
equivalent of a daily dose of 3 or 4 cups of coffee
(⬃350 mg of caffeine) increases the risk of ne-
phropathy in healthy subjects. Attention should
be paid to the categories of individuals who are at
a slightly higher risk, such as those with a clinical
or family history of kidney stones, children, and
elderly subjects who consume extra quotas of
caffeine during the day by taking medication or
drinks containing it. In these three categories, the
risk is linked above all to the possibility of reach-
ing an overdose of caffeine, thus incurring acute
(which is rare) or chronic renal damage. On the
other hand, in subjects with a predisposition, the
risk of lithiasis tends to be eliminated if a modest
consumption of caffeine substance is associated
with a rigorous diet and adequate water intake.
Finally, the positive effects of caffeine on men-
tal concentration, mood, and capacity to respond
to stress, and the taste of the most widely drunk
beverage in the world, represent a pleasure that
there is no reason for renouncing.
Moreover, who knows that the kidney, just
like the brain, may find that coffee is a precious
ally in its struggles! “A strong long coffee keeps me
awake and warms me, giving me unusual strength, a
suffering not free of pleasure. I would rather suffer than
be insensitive,” said Napoleon Bonapart on prais-
ing the extraordinary qualities of this beverage
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BOLIGNANO ET AL
when he realized that there was something tastier
and less damaging than alcohol that could help his
troops to address their daily challenges. We totally
agree with him.
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