Prevalent and new use of common drugs for the incidence of community-acquired acute kidney injury: cohort and case-crossover study.

Although community-acquired acute kidney injury (CA-AKI) represents a significant subset of all AKI incidence, evidence is limited due to the lack of comprehensive data prior to diagnosis. Here, we examined the risk of drug use for CA-AKI by using exhaustive pre-diagnostic prescription data. We included 78,754 working-age healthy individuals who underwent an annual health checkup program. We conducted a cohort study to assess the association between prevalent drug use and subsequent CA-AKI incidence using the Cox proportional hazard model. Subsequently, we conducted a case-crossover study to compare the new drug use in the case period directly before the CA-AKI incidence (- 3 to 0 months) with that in the control period far before the CA-AKI incidence (- 15 to - 12 months and - 9 to - 6 months) using the conditional Poisson regression model. The prevalent use of renin-angiotensin-aldosterone system (RAAS) inhibitors was associated with an increased CA-AKI incidence, but the new use was not. The new use of diuretics, anti-infectious drugs, and contrast medium was also associated with an increased CA-AKI incidence. These results suggest we need to pay attention for the incidence of AKI among the general population taking those common drugs.

[Renal failure and drug-drug interactions]. / Bei Niereninsuffizienz auf Arzneimittel-Interaktionen achten!

Renal failure is common and comes with a steep increasing prevalence in older patients. It is a frequent aspect in multimorbidity and associated with polypharmacia. Based on available literature an overview is given concerning important drug-drug interactions and how to avoid or manage them. Among a large variety of possible interactions anticoagulation and diuretic therapy still represent the highest clinical relevance.

Diuretics in pregnancy: Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC).

AIMS: Data on diuretic use in pregnancy are limited and inconsistent, and consequently it remains unclear whether they can be used safely. Our study aims to evaluate the perinatal outcomes after in-utero diuretic exposure. METHODS AND RESULTS: The Registry Of Pregnancy And Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with heart disease. Outcomes were compared between women who used diuretics during pregnancy versus those who did not. Multivariable regression analysis was used to assess the impact of diuretic use on the occurrence of congenital anomalies and foetal growth. Diuretics were used in 382 (6.7%) of the 5739 ROPAC pregnancies, most often furosemide (86%). Age >35 years (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-2.0), other cardiac medication use (OR 5.4, 95% CI 4.2-6.9), signs of heart failure (OR 1.7, 95% CI 1.2-2.2), estimated left ventricular ejection fraction <40% (OR 2.9, 95% CI 2.0-4.2), New York Heart Association class >II (OR 3.4, 95% CI 2.3-5.1), valvular heart disease (OR 6.3, 95% CI 4.7-8.3) and cardiomyopathy (OR 3.9, 95% CI 2.6-5.7) were associated with diuretic use during pregnancy. In multivariable analysis, diuretic use during the first trimester was not significantly associated with foetal or neonatal congenital anomalies (OR 1.3, 95% CI 0.7-2.6), and diuretic use during pregnancy was also not significantly associated with small for gestational age (OR 1.4, 95% CI 1.0-1.9). CONCLUSIONS: Our study does not conclusively establish an association between diuretic use during pregnancy and adverse foetal outcomes. Given these findings, it is essential to assess the risk-benefit ratio on an individual basis to guide clinical decisions.

Diuretics use in the management of hypertension.

Diuretics have been used for decades in the treatment of hypertension. Its efficacy has been demonstrated in numerous clinical trials. It is well known that the reduction in cardiovascular risk is a consequence of the reduction in blood pressure levels regardless of the drug used, but thiazide diuretics continue to be first-line drugs, especially in low doses and combined with other drugs. The debate on the advantages of using chlorthalidone or hydrochlorothiazide continues, however hydrochlorothiazide is drug most used and for which there is greater availability. The association with potassium-sparing diuretics increases the effectiveness and reduces the adverse reactions of thiazides. A new group of drugs, close to potassium-sparing diuretics, that antagonise aldosterone synthase are showing promising results as antihypertensives. There are no significant differences between men and women regarding the antihypertensive effect of thiazide diuretics.

Effects of thiazides and new findings on kidney stones and dysglycemic side effects.

Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.

Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study.

BACKGROUND: Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics. METHOD: This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I-III in Sweden in 2007-2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure. RESULTS: In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity. CONCLUSION: Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.

Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Incident Diuretic Use and Subsequent Risk of Bone Fractures: A Large Nationwide Observational Study of US Veterans.

OBJECTIVE: To investigate the association of incident use of diuretics with subsequent risk of incident bone fractures. PATIENTS AND METHODS: In a nationwide cohort of 863,339 US veterans receiving care from the VA health care system between October 1, 2004, and September 30, 2006, with follow-up through June 30, 2018, we examined the association of incident diuretic use (overall, and separately by thiazide, loop, and potassium-sparing diuretics) with subsequent risk of incident bone fractures using multivariable Cox regression models while minimizing confounding by indication using a target trial emulation approach. RESULTS: Patients were 63.3±12.9 years old; 93.5% (n=807,180) were male; and 27.1% (n=233,996) were diabetic. Their baseline estimated glomerular filtration rate was 84.4±16.5 mL/min per 1.73 m2. Among 863,339 patients, 424,386 (49.2%) newly initiated diuretics, of which 77.4% (n=328,524), 22.5% (n=95,457), and 0.1% (n=405) were thiazide, loop, and potassium-sparing diuretic users, respectively. After multivariable adjustments, incident diuretic use (vs non-use) was significantly associated with higher risk of incident fracture (adjusted HR [aHR], 1.14; 95% CI, 1.11 to 1.16). The association was most pronounced for loop diuretics (aHR, 1.39; 95% CI, 1.35 to 1.44) but less evident for thiazide diuretics (aHR, 1.08; 95% CI, 1.06 to 1.10) and was not significant for potassium-sparing diuretics (aHR, 0.97; 95% CI, 0.62 to 1.52). The diuretic-fracture association was more evident in younger (vs older) patients, those with (vs without) corticosteroid use, and those with lower (vs higher) serum sodium levels. CONCLUSION: Incident use of diuretics, particularly loop diuretics, was independently associated with higher risk of incident bone fractures. Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan.

BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.

Comparative safety and effectiveness of angiotensin converting enzyme inhibitors and thiazides and thiazide-like diuretics under strict monotherapy.

Previous work comparing safety and effectiveness outcomes for new initiators of angiotensin converting-enzyme inhibitors (ACEi) and thiazides demonstrated more favorable outcomes for thiazides, although cohort definitions allowed for addition of a second antihypertensive medication after a week of monotherapy. Here, we modify the monotherapy definition, imposing exit from cohorts upon addition of another antihypertensive medication. We determine hazard ratios (HR) for 55 safety and effectiveness outcomes over six databases and compare results to earlier findings. We find, for all primary outcomes, statistically significant differences in effectiveness between ACEi and thiazides were not replicated (HRs: 1.11, 1.06, 1.12 for acute myocardial infarction, hospitalization with heart failure and stroke, respectively). While statistical significance is similarly lost for several safety outcomes, the safety profile of thiazides remains more favorable. Our results indicate a less striking difference in effectiveness of thiazides compared to ACEi and reflect some sensitivity to the monotherapy cohort definition modification.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study.

BACKGROUND: Aging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. METHODS: A case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1-7 days and 181-187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. RESULTS: The study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70-4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47-5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15-26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82-66.64). CONCLUSIONS: NSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

Diuretic Use in Post-Kidney Transplant Patients: A Retrospective Chart Review.

BACKGROUND: The occurrence of delayed graft function (DGF) significantly enhances the possibility of both acute and chronic rejection of the transplanted organ, thereby reducing patient quality of life and survival rates. To prevent and manage oliguria in renal transplant patients, loop diuretics are presently commonly used. In our study, we assessed the possible impact of furosemide on the incidence of DGF among kidney transplant recipients. METHODS: A review of medical records was conducted to examine demographic characteristics and kidney transplant outcomes in an adult (older than 18 years old) population. The primary objective was to determine the incidence of delayed graft function (DGF), whereas the secondary objective was to compare the creatinine levels and estimated glomerular filtration rate (eGFR) at day 30 and day 90 post-transplantation in patients who were administered furosemide vs those who were not. RESULTS: This study included 330 patients who underwent kidney transplantation. Furosemide was administered to 169 (51.3%), whereas 161(48.7%) patients did not receive continued dose of diuretic postoperatively. The rate of DGF was significantly higher in patients who received furosemide than in those who did not (furosemide 44% vs 4%; P < .001). The eGFR was lower in the furosemide group compared to the no furosemide group at day 30 (56 ± 24 vs 71 ± 24 mL/min/1.73 m2, P < .001) and day 90 (66 ± 27 vs 78 ± 25 mL/min/1.73 m2, P < .001). CONCLUSIONS: Our results show that there is no benefit in treating an oliguric AKI with furosemide. Administration of furosemide, especially in high doses, may increase the risk of toxicity, delay dialysis, and increase the length of stay.

Could admission level of uric acid predict total diuretic dose in acute heart failure?

BACKGROUND: Recent studies have shown that increases in serum UA levels are associated with adverse clinical outcomes in patients with chronic heart failure (CHF); the aim of this study was to determine the relationship between serum uric acid and total diuretic dose received during hospitalization in hospitalized patients with acute exacerbation of heart failure. The main purpose of this study is to determine the role of uric acid as a biomarker that can be a substitute for pro-BNP in clinical evaluation and the need for diuretics in hospitalized patients with acute heart failure. METHODS: After approving the plan in the Research Council of the Heart Department and obtaining an ethical code from the Regional Committee on Research Ethics (Human Subjects Studies), the researcher referred to the archives of our center, the case of 100 patients diagnosed with acute heart failure. Cardiac patients were selected, and the information required for the study was collected using a pre-prepared data collection form, and the information was entered into SPSS software after categorization and appropriate analysis and statistical tests were performed on it. Were performed and in all statistical tests the statistical significance level was considered 0.05: RESULTS: 100 patients with acute heart failure were included in this study with a mean age of 63.43 ± 14.78 years. 66% of them were men. The mean dose of furosemide in these patients was 680.92 ± 377.47 mg and the mean serum uric acid level in these patients was 8.55 ± 2.50 mg / dL. In the study of the relationship between the variables, there was a significant relationship between the dose of furosemide received with the serum level of serum uric acid (P = 0.017, r = 0.248 and P = 0.009, r = -0.267, respectively). There is also a significant relationship between serum uric acid level and patient mortality (P = 0.013, r = 0.247). However this relationship lost its significance after multivariate analysis. CONCLUSION: There is a significant relationship between serum uric acid level and diuretic use. However, in-hospital mortality is not related to uric acid levels at admission.