Proton pump inhibitors and adverse effects in kidney transplant recipients: A meta-analysis

Boonpheng, Boonphiphop; Sharma, Konika; Mao, Michael A; Cheungpasitporn, Wisit

doi:10.5500/wjt.v9.i2.35

Cited by 13 publications

(20 citation statements)

References 51 publications

(69 reference statements)

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“…In a recently published meta-analysis, a similar risk of hypomagnesaemia among KTR was demonstrated (pooled OR = 1.56, 95% CI 1.19-2.05) [30]. This meta-analysis by Boonpheng et al was based on one published paper and seven abstracts presented at medical conferences.…”

Section: Discussionmentioning

confidence: 94%

Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients

Douwes

Gomes-Neto

Schutten

et al. 2019

JCM

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Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy.

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Section: Discussionmentioning

confidence: 94%

Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients

Douwes

Gomes-Neto

Schutten

et al. 2019

JCM

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“…9,33 With significantly higher rates of magnesium supplementation in the PPI arm, this study added to the body of evidence that PPI use significantly increases hypomagnesemia in the transplant population. 15,[18][19][20]25 The average time of receipt of PPI or H2RA was several years, despite the majority of patients having no documented GI issues or other compelling reason for therapy posttransplant. At this center, there is a pharmacist present in the outpatient clinic setting but due to high patient volumes not every patient is assessed at every visit by a pharmacist.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11] Previous studies of PPI use in the kidney transplant population have mainly evaluated the shortterm risk of rejection given that PPIs reduce gastric acidity and may alter absorption and serum levels of MPA. [12][13][14][15] Studies have demonstrated that the formulation of MPA may determine the effect of PPI co-administration, with mycophenolate mofetil (MMF) exhibiting significantly decreased area under the curve that has not been consistently seen with enteric-coated mycophenolate sodium (EC-MPS), although reductions in the active metabolite mycophenolic acid glucuronide have not been shown to consistently be impacted by PPI therapy with either formulation. 16,17 Other transplant studies have demonstrated associations between PPI use and hypomagnesemia, Clostridium difficile infections, iron deficiency anemia, and increased fracture risk.…”

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confidence: 99%

“…23,24 Most studies comparing the impact of PPI or H2RA use on renal function posttransplant report outcomes up to a year posttransplant. 14,15 Currently, the only study evaluating the effect of PPIs or H2RAs on long-term renal function demonstrated significantly worse kidney function in PPI treated patients but has not been published in full manuscript form. 25 The objective of this study was to comprehensively compare the long-term safety of PPI and H2RA therapy in kidney transplant recipients.…”

mentioning

confidence: 99%

“…However, these studies did not compare PPIs to H2RAs 18–22 and included relatively small cohorts 23,24 . Most studies comparing the impact of PPI or H2RA use on renal function posttransplant report outcomes up to a year posttransplant 14,15 . Currently, the only study evaluating the effect of PPIs or H2RAs on long‐term renal function demonstrated significantly worse kidney function in PPI treated patients but has not been published in full manuscript form 25 …”

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confidence: 99%

See 2 more Smart Citations

Choice of Acid Suppressant Therapy and Long‐Term Graft Outcomes After Kidney Transplantation

January¹,

Progar²,

Nesselhauf³

et al. 2020

Pharmacotherapy

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STUDY OBJECTIVE The purpose of this study was to comprehensively evaluate the long-term adverse effects of proton pump inhibitors (PPIs) compared with histamine-2 receptor antagonists (H2RAs) in kidney transplant recipients. METHODS This retrospective cohort compared 582 patients treated with PPI with 705 patients treated with H2RA and evaluated adverse effects throughout their course of acid suppressant therapy to a maximum of nine years posttransplant. The primary outcome of interest was renal function at 1 year posttransplant; secondary outcomes included renal function at 30 days, 3, 5, and 9 years posttransplant as well as rejection, electrolyte and laboratory abnormalities, osteoporosis, pneumonia, and Clostridium difficile infections. RESULTS Renal function did not significantly differ at any timepoint posttransplant. Rejection rates and Clostridium difficile infections were similar between groups; osteoporosis and pneumonia rates were numerically higher in the PPI treated arm but did not reach statistical significance. Proton pump inhibitor (PPI) treated patients were more likely to experience hypomagnesemia requiring supplementation. High dose PPI treated patients had significantly higher rates of pneumonia and osteoporosis compared with H2RA treated patients. Patients were maintained on PPI therapy for an average of 5 years and H2RA therapy for 3 years posttransplant, the majority without a clear indication for therapy. CONCLUSIONS There was no difference in renal function, rejection, or graft loss between PPI and H2RA treated patients. The majority of patients were maintained on PPI therapy for several years posttransplant without a clear indication; critical evaluation of ongoing need for acid suppressant therapy in the posttransplant course should be an area of future focus. KEY WORDS proton pump inhibitor, histamine-2 receptor antagonist, kidney transplantation.

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