Proton Pump Inhibitors and Adverse Effects in Kidney Transplant Recipients: A Meta-Analysis

BACKGROUND: The adverse renal effects of proton pump inhibitors (PPIs) are increasingly recognized in both the general population and patients with chronic kidney disease. Several pharmacokinetic studies have also raised concerns regarding the interaction between PPIs and immunosuppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear. We performed this meta-analysis to assess the risk of adverse effects in kidney transplant recipients on PPI compared with those without PPI exposure. AIM: To investigate the risk of acute rejection, graft loss, hypomagnesemia, renal dysfunction, and overall mortality in kidney transplant recipients on PPI compared with those without PPI exposure. METHODS: A systematic review was conducted in MEDLINE, EMBASE, and Cochrane databases from inception through October 2018 to identify studies that evaluated the adverse effects of PPIs in kidney transplant recipients, including biopsy-proven acute rejection, graft loss, hypomagnesemia, renal function, and overall mortality. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO, No. CRD42018115676. RESULTS: Fourteen observational studies with 6786 kidney transplant recipients were enrolled. No significant association was found between PPI exposure and the risk of biopsy-proven acute rejection at ≥ 1 year [pooled odds ratio (OR), 1.25; 95% confidence interval (CI), 0.82-1.91, = 55%], graft loss at 1 year (pooled OR = 1.30, 95%CI: 0.75-2.24, = 0%) or 1-year mortality (pooled OR = 1.53, 95%CI: 0.90-2.58, = 34%). However, PPI exposure was significantly associated with hypomagnesemia (pooled OR = 1.56, 95%CI: 1.19-2.05, = 27%). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias. CONCLUSION: PPI use was not associated with significant risks of higher acute rejection, graft loss, or 1-year mortality. However, the risk of hypomagnesemia was significantly increased with PPI use. Thus, future studies are needed to assess the impact of PPIs on long-term outcomes

Efficacy and Safety of SGLT-2 Inhibitors for Treatment of Diabetes Mellitus among Kidney Transplant Patients: A Systematic Review and Meta-Analysis

Background: The objective of this systematic review was to evaluate the efficacy and safety profiles of sodium-glucose co-transporter 2 (SGLT-2) inhibitors for treatment of diabetes mellitus (DM) among kidney transplant patients. Methods: We conducted electronic searches in Medline, Embase, Scopus, and Cochrane databases from inception through April 2020 to identify studies that investigated the efficacy and safety of SGLT-2 inhibitors in kidney transplant patients with DM. Study results were pooled and analyzed utilizing random-effects model. Results: Eight studies with 132 patients (baseline estimated glomerular filtration rate (eGFR) of 64.5 ± 19.9 mL/min/1.73 m2) treated with SGLT-2 inhibitors were included in our meta-analysis. SGLT-2 inhibitors demonstrated significantly lower hemoglobin A1c (HbA1c) (WMD = −0.56% [95%CI: −0.97, −0.16]; p = 0.007) and body weight (WMD = −2.16 kg [95%CI: −3.08, −1.24]; p < 0.001) at end of study compared to baseline level. There were no significant changes in eGFR, serum creatinine, urine protein creatinine ratio, and blood pressure. By subgroup analysis, empagliflozin demonstrated a significant reduction in body mass index (BMI) and body weight. Canagliflozin revealed a significant decrease in HbA1C and systolic blood pressure. In terms of safety profiles, fourteen patients had urinary tract infection. Only one had genital mycosis, one had acute kidney injury, and one had cellulitis. There were no reported cases of euglycemic ketoacidosis or acute rejection during the treatment. Conclusion: Among kidney transplant patients with excellent kidney function, SGLT-2 inhibitors for treatment of DM are effective in lowering HbA1C, reducing body weight, and preserving kidney function without reporting of serious adverse events, including euglycemic ketoacidosis and acute rejection

Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis

Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. Methods: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). Results: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8–13.4%, I2 = 0%) and 5.5% (95%CI: 2.9–10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6–34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2–36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger’s regression asymmetry test (p > 0.05 for all analyses). Conclusions: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS

Serum Chloride Levels at Hospital Discharge and One-Year Mortality among Hospitalized Patients

This study aimed to assess the one-year mortality risk based on discharge serum chloride among the hospital survivors. We analyzed a cohort of adult hospital survivors at a tertiary referral hospital from 2011 through 2013. We categorized discharge serum chloride; ≤96, 97–99, 100–102, 103–105, 106–108, and ≥109 mmoL/L. We performed Cox proportional hazard analysis to assess the association of discharge serum chloride with one-year mortality after hospital discharge, using discharge serum chloride of 103–105 mmoL/L as the reference group. Of 56,907 eligible patients, 9%, 14%, 26%, 28%, 16%, and 7% of patients had discharge serum chloride of ≤96, 97–99, 100–102, 103–105, 106–108, and ≥109 mmoL/L, respectively. We observed a U-shaped association of discharge serum chloride with one-year mortality, with nadir mortality associated with discharge serum chloride of 103–105 mmoL/L. When adjusting for potential confounders, including discharge serum sodium, discharge serum bicarbonate, and admission serum chloride, one-year mortality was significantly higher in both discharge serum chloride ≤99 hazard ratio (HR): 1.45 and 1.94 for discharge serum chloride of 97–99 and ≤96 mmoL/L, respectively; p < 0.001) and ≥109 mmoL/L (HR: 1.41; p < 0.001), compared with discharge serum chloride of 103–105 mmoL/L. The mortality risk did not differ when discharge serum chloride ranged from 100 to 108 mmoL/L. Of note, there was a significant interaction between admission and discharge serum chloride on one-year mortality. Serum chloride at hospital discharge in the optimal range of 100–108 mmoL/L predicted the favorable survival outcome. Both hypochloremia and hyperchloremia at discharge were associated with increased risk of one-year mortality, independent of admission serum chloride, discharge serum sodium, and serum bicarbonate

Acetazolamide Therapy in Patients with Heart Failure: A Meta-Analysis

Background and objectives: Fluid overload and central sleep apnea are highly prevalent in patients with heart failure (HF). We performed this meta-analysis to assess the effects of acetazolamide therapy on acid/base balance and apnea indexes. Methods: A literature search was conducted using EMBASE, MEDLINE, and Cochrane Database from inception through 18 November 2017 to identify studies evaluating the use of acetazolamide in HF. Study results were analyzed using a random effects model. The protocol for this systematic review is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017065401). Results: Nine studies (three randomized controlled trials and six cohort studies) with a total of 229 HF patients were enrolled. After acetazolamide treatment, there were significant decreases in serum pH (mean difference (MD) of −0.04 (95% CI, −0.06 to −0.02)), pCO2 (MD of −2.06 mmHg (95% CI, −3.60 to −0.53 mmHg)), and serum bicarbonate levels (MD of −6.42 mmol/L (95% CI, −10.05 to −2.79 mmol/L)). When compared to a placebo, acetazolamide significantly increased natriuresis (standardized mean difference (SMD) of 0.67 (95% CI, 0.08 to 1.27)), and decreased the apnea-hypopnea index (AHI) (SMD of −1.06 (95% CI, −1.75 to −0.36)) and central apnea index (CAI) (SMD of −1.10 (95% CI, −1.80 to −0.40)). Egger’s regression asymmetry tests revealed no publication bias with p = 0.20, 0.75 and 0.59 for analysis of the changes in pH, pCO2, and serum bicarbonate levels with use of acetazolamide in HF patients. Conclusion: Our study demonstrates significant reduction in serum pH, increase in natriuresis, and improvements in apnea indexes with use of acetazolamide among HF patients

The Association between Serum Uric Acid and Peripheral Neuropathy in Patients with Type 2 Diabetes Mellitus: A Multicenter Nationwide CrossSectional Study

Background: The role of uric acid in the development of diabetic peripheral neuropathy remains unclear. This study aimed to determine the association between uric acid and peripheral neuropathy among type 2 diabetes mellitus (T2DM) patients. Methods: We conducted a nationwide cross-sectional study based on the diabetes and hypertension study of the Medical Research Network of the Consortium of Thai Medical Schools. Adult T2DM patients from 831 public hospitals in Thailand were evaluated. The serum uric acid level was categorized into five groups based on quintiles (7.3 mg/dL). A multivariate logistic regression model was used to assess the independent association between serum uric acid level and peripheral neuropathy. Results: In total, 7,511 T2DM patients with available data about serum uric acid levels were included in the analysis. The mean age of the participants was 61.7 +/- 10.9 years, and approximately 35.6% were men. The prevalence rate of peripheral neuropathy was 3.0%. Moreover, the prevalence rates of peripheral neuropathy stratified according to uric acid levels 7.3 mg/dL were 2.5%, 2.8%, 2.4%, 2.5%, and 4.7%, respectively. A serum uric acid level >= 7.3 mg/dL was found to be associated with an increase in odds ratio (1.54; 95% confidence interval, 1.02-2.32) for peripheral neuropathy compared with a serum uric acid level <4.4 mg/dL. Conclusion: Serum uric acid level is independently associated with peripheral neuropathy in T2DM patients, and elevated serum uric acid levels should be considered a risk factor for diabetic peripheral neuropathy in clinical practice.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Risk of Hip Fracture in Patients on Hemodialysis Versus Peritoneal Dialysis: A Meta-Analysis of Observational Studies

Background: Bone and mineral metabolism disorders are common among end-stage renal disease (ESRD) patients, which could lead to hip fracture. It is unclear whether the hip fracture risk is different among patients on hemodialysis (HD) versus peritoneal dialysis (PD). This meta-analysis was conducted to evaluate the hip fracture risk in ESRD patients on HD, when compared to PD. Methods: A literature review was conducted in EMBASE, MEDLINE, and Cochrane databases through January 31, 2018 to identify studies that appraised the rate or risk of hip fracture among patients on HD, when compared to PD. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, generic inverse variance approach of DerSimonian and Laird. Results: Five cohort studies with 1 276 677 ESRD patients were enrolled. HD status was associated with a significantly higher risk of hip fracture with the pooled odds ratio (OR) of 1.61 (95% confidence interval [CI] 1.50-1.73, I2 = 10.0%), compared with PD. When the analysis was limited to studies with confounder-adjusted analysis, the pooled OR of hip fracture among HD patients was 1.57 (95% CI 1.43-1.72, I2 = 13.6%). Funnel plots and Egger\u27s regression test demonstrated no significant publication bias in our meta-analysis. Conclusions: Among ESRD patients, HD status is associated with a 61% higher risk of hip fracture compared to PD

Impact of Circadian Blood Pressure Pattern on Silent Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Background Abnormal circadian blood pressure (BP) variations during sleep, specifically the non-dipping (<10% fall in nocturnal BP) and reverse-dipping patterns (rise in nocturnal BP), have been associated with an increased risk of cardiovascular events and target organ damage. However, the relationship between abnormal sleep BP variations and cerebral small vessel disease markers is poorly established. This study aims to assess the association between non-dipping and reverse-dipping BP patterns with markers of silent cerebral small vessel disease. Methods and Results MEDLINE, Embase, and Cochrane Databases were searched from inception through November 2019. Studies that reported the odds ratios (ORs) for cerebral small vessel disease markers in patients with non-dipping or reverse-dipping BP patterns were included. Effect estimates from the individual studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Twelve observational studies composed of 3497 patients were included in this analysis. The reverse-dipping compared with normal dipping BP pattern was associated with a higher prevalence of white matter hyperintensity with a pooled adjusted OR of 2.00 (95% CI, 1.13-2.37; I=36%). Non-dipping BP pattern compared with normal dipping BP pattern was associated with higher prevalence of white matter hyperintensity and asymptomatic lacunar infarction, with pooled ORs of 1.38 (95% CI, 0.95-2.02; I=52%) and 2.33 (95% CI, 1.30-4.18; I=73%), respectively. Limiting to only studies with confounder-adjusted analysis resulted in a pooled OR of 1.38 (95% CI, 0.95-2.02; I=52%) for white matter hyperintensity and 1.44 (95% CI, 0.97-2.13; I=0%) for asymptomatic lacunar infarction. Conclusions The non-dipping and reverse-dipping BP patterns are associated with neuroimaging cerebral small vessel disease markers

Inpatient Burden and Mortality of Goodpasture's Syndrome in the United States: Nationwide Inpatient Sample 2003-2014

Background: Goodpasture's syndrome is a rare, life-threatening, small vessel vasculitis. Given its rarity, data on its inpatient burden and resource utilization are lacking. We conducted this study aiming to assess inpatient prevalence, mortality, and resource utilization of Goodpasture's syndrome in the United States. Methods: The 2003-2014 National Inpatient Sample was used to identify patients with a principal diagnosis of Goodpasture's syndrome. The inpatient prevalence, clinical characteristics, in-hospital treatment, end-organ failure, mortality, length of hospital stay, and hospitalization cost were studied. Multivariable logistic regression was performed to identify independent factors associated with in-hospital mortality. Results: A total of 964 patients were admitted in hospital with Goodpasture's syndrome as the principal diagnosis, accounting for an overall inpatient prevalence of Goodpasture's syndrome among hospitalized patients in the United States of 10.3 cases per 1,000,000 admissions. The mean age of patients was 54 ± 21 years, and 47% were female; 52% required renal replacement therapy, whereas 39% received plasmapheresis during hospitalization. Furthermore, 78% had end-organ failure, with renal failure and respiratory failure being the two most common end-organ failures. The in-hospital mortality rate was 7.7 per 100 admissions. The factors associated with increased in-hospital mortality were age older than 70 years, sepsis, the development of respiratory failure, circulatory failure, renal failure, and liver failure, whereas the factors associated with decreased in-hospital mortality were more recent year of hospitalization and the use of therapeutic plasmapheresis. The median length of hospital stay was 10 days. The median hospitalization cost was $75,831. Conclusion: The inpatient prevalence of Goodpasture's syndrome in the United States is 10.3 cases per 1,000,000 admissions. Hospitalization of patients with Goodpasture's syndrome was associated with high hospital inpatient utilization and costs.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Impact of admission serum ionized calcium levels on risk of acute kidney injury in hospitalized patients

This study aimed to investigate the risk of acute kidney injury (AKI) in hospitalized patients based on admission serum ionized calcium levels. This is a cohort study of all hospitalized adult patients, from January 2009 to December 2013 at a tertiary referral hospital, who had available serum ionized calcium at the time of admission. We excluded patients who had end-stage kidney disease or AKI at admission. We stratified admission serum ionized calcium into 6 groups;= 5.20 mg/dL. We used serum creatinine criterion of KDIGO definition for diagnosis of AKI. We performed logistic regression analysis to assess the risk of in-hospital AKI occurrence based on admission serum ionized calcium, using serum ionized calcium of 5.00-5.19 mg/dL as the reference group. We studied a total of 25,844 hospitalized patients. Of these, 3,294 (12.7%) developed AKI in hospital, and 622 (2.4%) had AKI stage 2 or 3. We observed a U-shaped association between admission serum ionized calcium and in-hospital AKI, with nadir in-hospital AKI was in serum ionized calcium of 5.00-5.19 mg/dL. After adjustment for confounders, low serum ionized calcium of 4.40-4.59,= 5.20 mg/dL were associated with increased risk of AKI with odds ratio of 1.33 (95% CI 1.14-1.56), 1.45 (95% CI 1.21-1.74), and 1.26 (95% CI 1.04-1.54), respectively. Both hypocalcemia, and hypercalcemia at the time of admission were associated with an increased risk of hospital-acquired AKI.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]