Thiazides for kidney stone recurrence prevention.

PURPOSE OF REVIEW: Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation. RECENT FINDINGS: The clinical routine to prescribe thiazides for kidney stone prevention has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of recurrence. Yet, adverse events such as new onset diabetes mellitus and gout were more common in patients receiving hydrochlorothiazide compared to placebo. As demonstrated by a novel meta-analysis presented in this review encompassing all randomized placebo-controlled trials with thiazide monotherapy, current trial evidence does not indicate that thiazide monotherapy is significantly better than placebo in preventing kidney stone recurrence. SUMMARY: Given the limited efficacy and possible adverse effects, we advocate for a restrictive use of thiazides for kidney stone recurrence prevention. Clearly, there remains a high unmet medical need for effective, targeted therapies to prevent recurrence of kidney stones.

Diuretic Tolerance to Repeated-Dose Furosemide in Infants Born Very Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To assess the presence and timing of furosemide diuretic tolerance in infants with bronchopulmonary dysplasia (BPD), and to determine if tolerance is modified by thiazide co-administration. STUDY DESIGN: We performed a retrospective cohort study among infants born very preterm with BPD exposed to repeated-dose furosemide for 72 hours, measuring net fluid balance (total intake minus total output) as a surrogate of diuresis in the 3 days before and after exposure. The primary comparison was the difference in fluid balance between the first and third 24 hours of furosemide exposure. We fit a general linear model for within-subject repeated measures of fluid balance over time, with thiazide co-administration as an interaction variable. Secondary analyses included an evaluation of weight trajectories over time. RESULTS: In 83 infants, median fluid balance ranged between + 43.6 and + 52.7 ml/kg/d in the 3 days prior to furosemide exposure. Fluid balance decreased to a median of + 29.1 ml/kg/d in the first 24 hours after furosemide, but then increased to +47.5 ml/kg/d by the third 24-hour interval, consistent with tolerance (P < .001). Thiazides did not modify the change in fluid balance during furosemide exposure for any time-period. Weight decreased significantly in the first 24 hours after furosemide and increased thereafter (P < .001). CONCLUSIONS: The net fluid balance response to furosemide decreases rapidly during repeated-dose exposures in infants with BPD, consistent with diuretic tolerance. Clinicians should consider this finding in the context of an infant's therapeutic goals. Further research efforts to identify safe and effective furosemide dosage strategies are needed.

Comparative analysis of real-world adherence and persistence patterns with vibegron, mirabegron, and anticholinergics in patients with overactive bladder: A retrospective claims study.

INTRODUCTION: Vibegron is a selective ß3-adrenergic receptor agonist that was approved by the US Food and Drug Administration in December 2020 for the treatment of overactive bladder in adults. This retrospective study assessed US pharmacy claims data to evaluate the real-world adherence and persistence of vibegron compared with mirabegron and with anticholinergics. MATERIALS AND METHODS: This analysis used the Optum Research Database to identify adults with ≥1 pharmacy claim for vibegron, mirabegron, or an anticholinergic from April 1, 2021, to August 31, 2022. Patients had ≥ 90 days of continuous commercial or Medicare medical and pharmacy coverage preindex and ≥ 60 days of continuous pharmacy coverage postindex. Two independent propensity-score models matched patients treated with (1) vibegron versus mirabegron and (2) vibegron versus anticholinergics on key variables such as demographics and clinical characteristics, index copay, days' supply, and time of entry into analysis (index quarter). Adherence was measured by proportion of days covered (PDC) from index to the end of follow-up and was defined as PDC ≥ 80%. Persistence was defined as days to discontinuation of index medication (first 30-day gap) or end of follow-up. RESULTS: The matched vibegron and mirabegron cohorts included 4921 and 9842 patients, respectively, and the matched vibegron and anticholinergic cohorts included 4676 and 9352 patients, respectively. Patients receiving vibegron had greater mean PDC versus patients receiving mirabegron (0.67 vs. 0.64, respectively; p < 0.001) or anticholinergics (0.67 vs. 0.58; p < 0.001). A greater percentage of patients receiving vibegron were adherent versus those receiving mirabegron (49.0% vs. 45.1%, respectively; p < 0.001) or anticholinergics (49.1% vs. 38.5%; p < 0.001). Persistence was longer with vibegron compared with both mirabegron (median [95% CI], 171 [159-182] vs. 128 [122-137] days, respectively; p < 0.001) and anticholinergics (172 [159-183] vs. 91 [91] days; p < 0.001). CONCLUSION: In this retrospective analysis of pharmacy claims data, patients receiving vibegron exhibited significantly higher adherence and demonstrated longer persistence in comparison to matched patient cohorts receiving either mirabegron or anticholinergics.

Thiazides do not affect mortality but may reduce CV events vs. nondiuretic antihypertensive drugs at up to 5 y.

SOURCE CITATION: Reinhart M, Puil L, Salzwedel DM, et al. First-line diuretics versus other classes of antihypertensive drugs for hypertension. Cochrane Database Syst Rev. 2023;7:CD008161. 37439548.

[Thiazid diuretics : some useful considerations in clinical practice]. / Diurétiques thiazidiques. Quelques considérations utiles en pratique clinique.

Thiazide diuretics are an essential part of the treatment of hypertension, which affects nearly a third of the world's population. Hydrochlorothiazide is the most widely used member of this class, due to its long availability on the market and the many combinations available with other substances. Other analogues of this class exist, with notable advantages from a clinical point of view, recognized under the name of thiazide-like. This article reviews some of the considerations in clinical practice concerning the different types of thiazides currently available in Switzerland.

Les diurétiques thiazidiques font partie des traitements de premier choix dans la prise en charge de l'hypertension artérielle, touchant près d'un tiers de la population mondiale. L'hydrochlorothiazide est le représentant de cette classe médicamenteuse le plus utilisé dans les combinaisons antihypertensives en Suisse. D'autres analogues de cette classe existent sur le marché, avec des avantages notables du point de vue clinique, reconnus sous la dénomination de thiazides-like. Le choix de l'utilisation d'un diurétique thiazidique repose avant tout sur les indications et les contre-indications relatives à cette classe. Cet article propose une revue de quelques considérations en pratique clinique sur les différents types de thiazides actuellement disponibles en Suisse.

Influence of administration time and sex on natriuretic, diuretic, and kaliuretic effects of diuretics.

Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes. That regulation is sexually dimorphic; as such, sex and time of day are not two independent regulators of kidney function and blood pressure. The objective of the present study was to assess the effect of sex and administration time on the natriuretic and diuretic effects of loop, thiazide, and K+-sparing diuretics, which are common treatments for hypertension. Loop diuretics inhibit Na+-K+-2Cl- cotransporters on the apical membrane of the thick ascending limb, thiazide diuretics inhibit Na+-Cl- cotransporters on the distal convoluted tubule, and K+-sparing diuretics inhibit epithelial Na+ channels on the connecting tubule and collecting duct. We simulated Na+ transporter inhibition using sex- and time-of-day-specific computational models of mouse kidney function. The simulation results highlighted significant sex and time-of-day differences in the drug response. Loop diuretics induced larger natriuretic and diuretic effects during the active phase. The natriuretic and diuretic effects of thiazide diuretics exhibited sex and time-of-day differences, whereas these effects of K+-sparing diuretics exhibited a significant time-of-day difference in females only. The kaliuretic effect depended on the type of diuretics and time of administration. The present computational models can be a useful tool in chronotherapy, to tailor drug administration time to match the body's diurnal rhythms to optimize the drug effect.NEW & NOTEWORTHY Sex influences cardiovascular disease, and the timing of onset of acute cardiovascular events exhibits circadian rhythms. Kidney function also exhibits sex differences and circadian rhythms. How do the natriuretic and diuretic effects of diuretics, a common treatment for hypertension that targets the kidneys, differ between the sexes? And how do these effects vary during the day? To answer these questions, we conducted computer simulations to assess the effects of loop, thiazide, and K+-sparing diuretics.

Effectiveness of thiazide and thiazide-like diuretics in advanced chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Thiazide diuretics are first-line drugs for the treatment of hypertension, but hypertension treatment guidelines have systematically discouraged their use in patients with advanced chronic kidney disease (CKD). For the first time, a systematic review and random-effects meta-analysis were performed to assess the effectiveness of thiazides and thiazide-like diuretics to treat hypertension in patients with stages 3b, 4, and 5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review and random-effects meta-analysis that included a literature search using the following databases were performed: MEDLINE through PubMed, Cochrane Database of Systematic Reviews (CDSR) and Cochrane Central Register of Controlled Trials (CENTRAL) through the Cochrane Library, Embase, and ISI - Web of Science (all databases). Prospective studies that evaluated the effectiveness of thiazide and thiazide-like diuretics in individuals with a GFR < 45 mL/min/1.73 m2 were included. RESULTS: Five clinical trials, totaling 214 participants, were included, and the mean GFR ranged from 13.0 ± 5.9 mL/min/1.73 m2 to 26.8 ± 8.8 mL/min/1.73 m2. There was evidence of a reduction in mean blood pressure and in GFR, as well as in fractional sodium excretion and fractional chloride excretion. CONCLUSION: Thiazide and thiazide-like diuretics seem to maintain their effectiveness in lowering blood pressure in patients with advanced chronic kidney disease. These findings should spur new prospective randomized trials and spark discussions, particularly about upcoming hypertension guidelines.

[Efficacy and Organoprotection of Triple Combinations in the Treatment of Arterial Hypertension].

The 2022 draft Russian guidelines on arterial hypertension recommend initiation of antihypertensive therapy with a combination of drugs in most patients with blood pressure above 150 / 90 mm Hg and / or in the presence of high-risk criteria. In 2021, the results of a 12-year analysis of the Brisighella Heart Study (BHS) were published. The aim of this study was to compare the use of different triple antihypertensive drug combinations in an Italian cohort of patients in real-life clinical practice. Combination antihypertensive therapy with a renin-angiotensin-aldosterone system inhibitor, amlodipine, and thiazide/thiazide-like diuretics provides a better blood pressure control compared to other antihypertensive drug combinations. The use of the triple combination of amlodipine/indapamide/perindopril is associated with a better metabolic profile than any other considered combination of antihypertensive drugs and a more pronounced organ-protective effect.

Revisiting diuretic choice in chronic kidney disease.

PURPOSE OF REVIEW: Existing guidelines offer little direction about the use of thiazide and loop diuretics in patients with chronic kidney disease (CKD). This review summarizes recent studies impacting indications and safety considerations for these agents in patients with CKD. RECENT FINDINGS: Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower glomerular filtration rates (GFR). Existing studies show no clear impact of thiazide or loop diuretic use on kidney or cardiovascular outcomes in patients with CKD. Sodium-glucose co-transporter type 2 (SGLT2) inhibitors have diuretic effects, but concomitant use of a diuretic does not diminish the preventive benefits of these agents against acute kidney injury (AKI). Despite theoretical concerns, thiazide diuretics likely do not worsen circulating vasopressin levels or cyst progression in polycystic kidney disease and may be useful for alleviating polyuria from tolvaptan. Diuretics cause multiple adverse effects, including electrolyte abnormalities, hemodynamic-mediated decrease in estimated GFR, and AKI. SUMMARY: Recent evidence supports expanded indications for diuretics in patients with kidney disease, including chlorthalidone for hypertension in advanced CKD. Monitoring electrolytes and estimated GFR is critical to ensure patient safety when prescribing these agents for patients with CKD.

Effect of diuretics on plasma aldosterone and potassium in primary hypertension: A systematic review and meta-analysis.

AIM: By contrast with drugs inhibiting the renin-angiotensin-aldosterone system (RAAS), diuretics stimulate renin release by the kidneys. Although plasma aldosterone (PA) is thought to be mainly regulated by RAAS activity, serum potassium has been shown to be an important factor in animal models and humans. Here we perform a systematic review and meta-analysis of randomised controlled trials (RCT) in hypertension investigating the effects of diuretic therapy on PA and the correlation of change in PA with that of potassium and blood pressure (BP). METHODS: Three databases were searched: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). Titles were first screened by title and abstract for relevance before full-text articles were assessed for eligibility according to a predefined inclusion/exclusion criteria. RESULTS: A total of 1139 articles were retrieved, of which 42 met the prespecified inclusion/exclusion criteria. The average standardised difference in mean PA was similar for all classes of diuretic: thiazide/thiazide-like 0.299 (95% confidence interval [CI] 0.150, 0.447), loop 0.927 (0.37, 1.49), MRA/potassium-sparing 0.265 (0.173, 0.357) and combination 0.466 (0.137, 0.796), Q = 6.33, P = .097. In subjects untreated with another antihypertensive, there was a significant relationship between change in PA and change in systolic BP but no relationship with the change in potassium. CONCLUSION: In RCTs of diuretic therapy in hypertension, there is an increase in PA with all classes of diuretic and no significant between-class heterogeneity. Change in PA is not related with potassium but correlates with the change in BP in subjects untreated with another antihypertensive medication.

Cardio-renal interaction - Clinical trials update 2022.

AIMS: Chronic kidney disease is a common cardiovascular risk indicator and strongly associated with increased morbidity and mortality. The heart and kidneys are pathophysiologically closely connected, which becomes particularly obvious in patients with cardiorenal syndrome. This review summarizes clinically relevant studies on the cardio-renal interaction published in 2021 and 2022. DATA SYNTHESIS: Selected trials published in high-impact journals were chosen from the database Pubmed and included in this review. New evidence about the selective mineralocorticoid receptor antagonist finerenone and the renoprotective sodium-glucose co-transporter-2-inhibitors (SGLT2-Inhibitors) are discussed and we update on novel insights about the treatment of arterial hypertension in patients with severe chronic kidney disease with the thiazide-like diuretic chlorthalidone. Finally, data on infective endocarditis in patients on chronic hemodialysis and the treatment of secondary hyperparathyroidism with the calcimimetic drug etelcalcetide in patients with end stage kidney disease are critically reviewed. CONCLUSION: Several important studies investigating cardio-renal interactions were recently published may affect clinical practice. The graphical abstract (Fig. 1) depicts the most relevant clinical studies investigating cardio-renal interactions.

Current antihypertensive treatment and treatment-resistant hypertension in Japanese patients with chronic kidney disease.

BACKGROUND: Hypertension is an important prognostic predictor in patients with chronic kidney disease (CKD), and the recommended target blood pressure has been continuously revised. This study aimed to reveal the current antihypertensive practices in Japanese patients with CKD. METHODS: In the Fukuoka Kidney disease Registry, we extracted 3664 non-dialysis-dependent patients with CKD. Apparent treatment-resistant hypertension (aTRH) was defined as a failure of blood-pressure control treated with three antihypertensive medication classes or a treatment with ≥ 4 classes regardless of blood pressure. The blood-pressure control complied with the target blood pressure recommended by the KDIGO 2012 guideline. RESULTS: The median age of the patients was 67 years, body mass index (BMI) was 23 kg/m2, and estimated glomerular filtration rate (eGFR) was 40 mL/min/1.73 m2. The number of patients with unachieved blood-pressure control was 1933, of whom 26% received ≥ 3 classes of antihypertensive medications. The first choice of medication was renin-angiotensin system inhibitors, followed by calcium-channel blockers. The rate of thiazide use was low in all CKD stages (3-11%). The prevalence of aTRH was 16%, which was significantly associated with BMI (odds ratio [95% confidence interval] per 1-standard deviation change, 1.38 [1.25-1.53]), decreased eGFR (1.87 [1.57-2.23]), as well as age, diabetes mellitus, and chronic heart disease. CONCLUSIONS: Renal dysfunction and obesity are important risk factors of aTRH. Even under nephrologist care, most patients were treated with insufficient antihypertensive medications. It is important to prescribe sufficient classes of antihypertensive medications, including diuretics, and to improve patients' lifestyle habits.

Use of Thiazides to Treat Hypertension and Advanced CKD.

PURPOSE OF REVIEW: Hypertension is often difficult to control in patients with CKD as manifested by suboptimal control rates in this population. Use of thiazides in CKD patients has been limited as these agents are thought to be ineffective in reducing blood pressure in people with advanced CKD. This review summarizes recent studies impacting indications and safety of use of thiazide in patients with CKD and discusses the mechanism of how thiazides reduce blood pressure. RECENT FINDINGS: Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower levels of GFR. Recent clinical trial data indicate that thiazides are effective in patients with advanced kidney disease for blood pressure lowering. However, monitoring of electrolytes and kidney function is important to ensure patient safety when prescribing these agents in patients with CKD.

[Treatment of patients with arterial hypertension in clinical practice in 2010-2020 (according to the national register of hypertension)].

AIM: To analyze therapy in patients with arterial hypertension (AH) in 20102020. MATERIALS AND METHODS: Data of hypertensive patients observed in primary health care, entered into the base of hypertension registry for 20102020 years in the whole group (n=44 653) and in a separate subgroup of hypertensive patients in the absence of: ischemic heart disease, a history of myocardial infarction, chronic heart failure (n=20 569). RESULTS: About 80% of hypertensive patients are patients of high and very high risks (from 2010 to 2020, the proportion of very high cardiovascular risk (CVR) increased from 18.1 to 57.3%). The number of hypertensive patients with a history of myocardial infarction increased in 5 times, in 3 times with ischemic heart disease and with chronic heart failure. The number of prescribed drugs increased: mineralocorticoid receptor antagonist (in 5.8 times), loop diuretics (in 7.2) angiotensin receptor blockers (in 3 times), b-adrenoblockers, calcium channel blockers of the dihydropyridine series, thiazide-like diuretics in 2 times. Patients at high and very high risk are more likely reached target blood pressure values. Angiotensin-converting enzyme inhibitors were prescribed in more than 70% of patients with hypertension and the absence of coronary heart disease, chronic heart failure, history of myocardial infarction; the prescription of b-adrenoblockers, angiotension receptor blockers, thiazide-like and loop diuretics increased. CONCLUSION: The proportion of more severe and comorbid patients has increased in observed in primary health care patients with AH over a 10-year period (20102020). This was probably the main factor of increasing antihypertensive therapy and prescribing drugs with additional indications and improving the achievement of target blood pressure in patients with high and very high cardiovascular risk.

The Forgotten Antiproteinuric Properties of Diuretics.

BACKGROUND: Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. SUMMARY: Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.

[Tactics of antihypertensive therapy during COVID-19 pandemic].

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

Long-term thiazide use and risk of low-energy fractures among persons with Alzheimer's disease-nested case-control study.

We investigated the association between thiazide use and the risk of low-energy fractures among community dwellers with Alzheimer's disease. Longer use was associated with a decreased risk of low-energy fractures. This study extends the previous knowledge of reduced fracture risk of thiazides to persons with Alzheimer's disease. INTRODUCTION: To investigate the association between thiazide use and the risk of low-energy fractures (LEF), and hip fracture among community dwellers with Alzheimer's disease (AD). No prior study has evaluated the effect of thiazides on LEF risk of AD patients. METHODS: LEF cases were identified from the MEDALZ study, including all community-dwelling persons diagnosed with AD in Finland 2005-2011. During the follow-up from AD diagnoses until the end of 2015, cases with LEF (N = 10,416) and hip fracture (N = 5578) were identified. LEF cases were matched with up to three controls without LEF, according to time since AD diagnosis, age and gender. Thiazide use identified from the Prescription register data was modeled with PRE2DUP method. Current use was defined in 0-30 days' time window before the fracture/matching date, and duration of current use was assessed. The association between thiazide exposure and LEFs was assessed with conditional logistic regression. RESULTS: Current thiazide use was observed in 10.5% of LEF cases and 12.5% of controls. Current thiazide use was associated with a decreased risk of LEF (adjusted OR [aOR] 0.83, 95% CI 0.77-0.88). In terms of the duration of use, no association was observed with short-term use (< 1 year or 1-3 years), while longer use (> 3 years) was associated with a reduced risk of LEF (aOR 0.77, 95% CI 0.71-0.83) and hip fracture (aOR 0.68, 95% CI 0.60-0.78). CONCLUSIONS: Our study extends the previous knowledge of reduced fracture risk of thiazides to persons with AD, a population with significantly increased background risk of fractures.

Electrolyte imbalance after total joint arthroplasty: risk factors and impact on length of hospital stay.

BACKGROUND: Clinical as well as subclinical hyponatremia is frequently seen after orthopedic surgery. The study was aimed to determine the frequency and severity of hyponatremia in a cohort of total joint arthroplasty cases and identify the risk factors and their impact. METHODS: This is a retrospective observational study of 546 consecutive cases of total joint arthroplasty patients from a single institution. Only primary hip and knee replacements were included. The study was approved by the institutional review board. Preoperative and postoperative serum electrolytes were recorded till 45-day review. This was correlated with the age, gender, BMI, drug intake, and comorbidities. RESULTS: We identified 84.9% postsurgical hyponatremia in our cohort. Of these 80% were mild, 16% moderate and 4% severe. Preoperative hyponatremia was a consistent finding in most severe cases. Thaizides, ACE inhibitors, and longer surgeries like bilateral TKRs had more hyponatremia. Hospital stay was not impacted in this study for reasons discussed. There were no deaths in this series during the follow-up period, but two patients were rehospitalized. CONCLUSION: Postsurgical hyponatremia occurs in up to 85% of primary hip and knee arthroplasty patients. The most consistent predictor of severe electrolyte disturbance postsurgery is preoperative hyponatremia. Older age, female gender, longer surgery, and drugs like thiazides and ACE inhibitors seemed contributory.