Study: Proton pump inhibitor in connection with chronic kidney disease

Lazarus B., Chen Y., Wilson F. et al. Use of proton pump inhibitors and the risk of chronic kidney disease. Jama internal med . 2016; 176 (2): 238-246.

assessment of a possible correlation between the use of proton pump inhibitors (PPI) and the incidence of chronic kidney disease (CKD).

Observation study to pursue the glomerular filtration rate (GFR) of PPI users compared to non-users.

The study included 10,482 subjects who took part in the Atherosclerosis Risk in Communities (ARIC) study. All subjects had a GFR of more than 60 ml/min/1.73 m 2 at the beginning of the course. The average age was 63.0 years; 43.9 % were male and 3,229 (3.1 %) took PPI at the beginning of the course. The median post -observation period was 13.9 years.

Regardless of this, a replication of 248,751 subjects in the Geising Health System in Pennsylvania was observed over a median of 6.2 years. All participants had a normal (> 60 ml/min/1.73 m 2 ) GFR in recruitment. At the beginning of the study, 16,900 (6.8 %) took PPI.

The incidence of CKD was defined by a GFR of less than 60 ml/min/1.73 m 2 or by diagnostic codes during hospital discount or death.

The visits at the beginning of the course took place between February 1, 1996 and January 30, 1999. The patients were traced by December 31, 2011. In the Aric covenant, participants who used PPIs at the beginning of the course had a 45 % higher risk of developing CNE [HR (Hazard Ratio): 1.45; 95% CI (Confidence interval): 1.11-1.90)] as a non-user. When taking demographic, socio-economic and clinical variables into account, the risk was similar, with a 50 % higher CKD risk in PPI users compared to non-users (HR: 1.50; 95 %-KI: 1.14–1.96). When Baseline-PPI users were compared to users of H2 antagonists, the association remained; Compared to users of H2 antagonists, PPI users had a 39 % increased risk of developing a chronic kidney disease (HR: 1.39; 95 % KI: 1.01-1.91).

The Geisinger health system cohort confirmed the aric cohort. The application of PPIs was associated with CKD, with a dose -dependent increase in association. Those who revenue twice a day (adapted HR: 1.46; 95 % AI: 1.28–1.67) had a higher CKD risk than those who revenue once a day (adapted HR: 1.15; 95 % KI: 1.09–1,21).

The use of proton pump inhibitors is a risk factor for CNE; In this study, PPI users had a greater incidence of CKD as a non-user at the beginning of their studies. However, PPI users were also rather obese and occupied blood pressure-lowering medication, which indicates other risk factors. When the data were analyzed to adapt the Hazard Ratio and compare users and non-users with a similar CNE risk, the connection between PPI application and incidence remained. The risk was also dose -dependent: the twice daily gift was associated with a higher risk of the occurrence of a CKD than the once daily gift.

The use of proton pump inhibitors was previously considered relatively harmless, and many patients remember that they were told that there were no side effects. These are some of the most frequently prescribed medication, with more than 15 million Americans use PPI medication. It is estimated that 70 % of these recipes are unnecessary. ^{1 This does not even count the over-the-counter PPI medication that are available without a prescription. The author also sees many kidney patients who are treated with prednison because of glomerulonephritis and at the same time maintain PPI prophylactically against stomach.}

Many patients unnecessarily occupy PPIs. For those who actually suffer from Gerd, there are many treatment alternatives that should be considered before using PPI.

It is unclear whether the application of PPI and the associated CKD risk are due to direct nephrotoxicity or whether other risk factors associated with the use of PPI medication are responsible. In the study examined, the statistical analysis of old, obesity, socio -economic status and taking high blood pressure medication into account. Overall, the association hardly changed if these parameters were taken into account (45% increased CKD risk compared to 50%). Patients with gastroesophageal reflux (Gerd) also have a metabolic syndrome and endocrine dysfunction, so that these comorbidities may have contributed to the prevalence of CKD in PPI users. In addition, a high body mass index (BMI), high triglycerides and a low HDL value are associated with Gerd, so that this may also have influenced the risk of kidney dysfunction. ^{2 Since diabetes is by far the most common cause of kidney failure, the maintenance of a normal BMI is important for all risk patients.}

Another risk factor for CKD is hypothyroidism, and those with hypothyroidism have a higher incidence of Gerd. It is believed that this is more due to motility problems and / or hiatus hernia than over acidification. 3 , conversely, CKD patients have a higher incidence of a low thyroid function. A study suggested that hypothyroidism increases gradually with progressively lower glomerular filtration.

Although the connection between chronic kidney disease and PPI intake is newly established, the connection between acute kidney disease and PPI intake is known. Of all biopsy valleys with proven acute interstitial nephritis (AIN), 70 % are caused by medication, including PPIs. ^{5 In addition, a longer duration of drug use was associated with poor recovery. Lymphoplasmic infiltrations that affected the interstitium, with the glomerules were spared. 6 This indicates that the architecture of the kidney filter system is directly damaged, which delivers a plausible causality in connection between CKD and long-term PPI application.}

A natural active ingredient can have a profound effect in reducing Gerd's symptoms and at the same time people with CNE benefit: melatonin. An often overlooked feature of CNI is insomnia and melatonin production is affected by CNI. There is indications that the administration of exogenous melatonin can positively influence the course of CKD. The enterochromaffins cells of the gastrointestinal tract but 400 times as much melatonin as the pineal gland. Melatonin was part of successful natural protocols to treat Gerd without PPIs. 8 This is most likely due to the inhibition of nitrogen oxide synthesis, which causes a transient relaxation of the lower esophageal sphincter (Tlesr).

summarizing Gerd and CNI several common risk factors. Those who use PPI treatment for Gerd may already be exposed to a CNI risk. However, there is indications that the use of PPI can be harmful in and of itself. Many patients unnecessarily take PPIs. For those who actually suffer from Gerd, there are many treatment alternatives that should be considered before using PPI.

1. Kelly Jc. Proton pump inhibitors can increase the risk of kidney disease. Medscape website. http://www.medscape.com/viewarticle/857060#vp_2 . Published on January 11, 2016. Access on March 9, 2016.
2. m. Nomura, N. Tashiro, T. Watanabe et al. Association of symptoms of gastroesophageal reflux with metabolic syndrome parameters in patients with endocrine diseases. Isrn Gastroenterol . 2014: 863206. DOI: 10.1155/2014/863206.
3. Savina LV, Semenikhina TM, Korochanskaia NV, Klitinskaia is, Iakovenko MS. Hiatushernie and gastroesophageal reflux disease as a manifestation of newly discovered hypothyroidism [in Russian]. clin med (mosque) . 2006; 84 (2): 71-74.
4. Rheee cm, Kalantar-Zadeh K, Streja e, et al. The relationship between thyroid function and valued glomerular filtration rate in patients with chronic kidney disease. nephrol dial transplantation . 2015; 30 (2): 282-287.
5. Muriithi AK, Leung N, Valeri Am, et al. Acute interstitial nephritis, 1993-2011: a fall series. at the J Kidney Dis . 2014; 64 (4): 558-566.
6. Sampathkumar K, Ramalingam R, Prabakar A, Abraham A. Acute interstitial nephritis by proton pump inhibitors. Indian J Nephrol . 2013; 23 (4): 304-307.
7. Quiroz y, Ferrebuz A, Romero F, Vaziri ND, Rodriguez-ITURBE B. at the J Physiol Renal Physiol. 2008; 294 (2): F336-344.
8. Webach Mr. Melatonin for the treatment of gastroesophageal reflux disease. aging Ther Health Med . 2008; 14 (4): 54-58.
9. Pereira rs. Regression of the symptoms of gastroesophageal reflux disease due to dietary supplements with melatonin, vitamins and amino acids: comparison with omeprazole. j Zirbel gland res . 2006; 41 (3): 195-200.

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