Kidney function and coffee consumption: CYP1A2 variants play a decisive role

Caffeine has long been suspected of contributing to kidney dysfunction. A new study has investigated the role of genetic variations of the caffeine-eliminating cytochrome CYP1A2.

A study on coffee and kidneys is assessed

Long-term study included about 10 years of follow-up.
The CYP1A2 genotype was determined for each participant.
Coffee consumption was determined by questionnaires.
Albuminuria and hyperfiltration served as markers for renal dysfunction.
Only in the group of slow metabolisers* (who drank more than three cups of coffee per day) there was a significantly increased risk of renal dysfunction and hypertension.

CYP1A2 genotypes determine metabolic activity

CYP1A2 takes over the detoxification of caffeine in the human body. There are different genotypes that control the speed of this metabolism:

Genotype AA - occurred in about 43% of the study participants.
Genotype AC - was the second most common in the study population, with about 41%.
Genotype CC - was found in about 16% of the study participants.

People with the AC and CC variants are considered slow metabolisers of caffeine.

Study population from the HARVEST study

The data were taken from the Italian Hypertension and Ambulatory Recording Venetia Study (HARVEST), whose cohort included people with grade 1 hypertension and a study period of more than 16 years.

Sufficient information on coffee consumption, CYP1A2 genotype, and urine samples was available from 604 participants, hence these were evaluated in the current study.

Classification of kidney function and coffee consumption

In the study, renal dysfunction was defined as

Albuminuria with more than 30 mg albumin excretion over 24 hours.
Hyperfiltration with a GFR of more than 150 ml/min/1.73m2

Coffee consumption was divided into:

less than one cup per day (26% of participants).
one to three cups per day (63%).
more than three cups per day (11%).

In addition, the CYP1A2 genotype was determined and blood pressure was checked regularly. The genotype distribution was approximately equal across all three coffee consumption groups.

Coffee consumption: only relevant for slow-metabolisers

The data showed that for the cohort as a whole or the fast-metabolizers, coffee consumption was irrelevant for the risk of developing renal dysfunction or hypertension.

However, for the slow-metabolizers, those with genotype AC or CC, there was a significantly increased risk of albuminuria, hyperfiltration and hypertension - if they consumed more than three cups of coffee per day.

Conclusion for medical practice

The study showed that increased coffee consumption can indeed be harmful to the kidneys. However, this only seems to apply to people who are susceptible, due to the genetic variation in CYP1A2.

* Slow- as opposed to fast-metabolisers (slow or fast metabolisers).

Source:

Mahdavi S, Palatini P, El-Sohemy A. CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction. JAMA Netw Open. 2023 Jan 3;6(1):e2247868. doi: 10.1001/jamanetworkopen.2022.47868. PMID: 36701157.