Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.

Background and Objectives: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. Materials and Methods: After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. Results: A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older (p = 0.007) and have a higher prevalence of diabetes (p < 0.001) and hypertension (p = 0.030), higher systolic blood pressure (p = 0.011), and higher endocan levels (p < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, p < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, p = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, p = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, p < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (ß = 0.405, adjusted R2 change = 0.152; p < 0.001). Conclusions: The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.

Serum Malondialdehyde-Modified Low-Density Lipoprotein as a Risk Marker for Peripheral Arterial Stiffness in Maintenance Hemodialysis Patients.

Background and Objectives: Peripheral arterial stiffness (PAS), assessed by brachial-ankle pulse wave velocity (baPWV), is an independent biomarker of cardiovascular diseases (CVD) in patients on maintenance hemodialysis (HD). Malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidative stress marker, has been linked to atherosclerosis and CVD. However, the association between serum MDA-LDL and PAS among HD patients has not been fully elucidated. This study aimed to examine the association of serum MDA-LDL with PAS in HD patients and to identify the optimal cutoff value of serum MDA-LDL for predicting PAS. Materials and Methods: A cross-sectional study was conducted in 100 HD patients. Serum MDA-LDL was quantified using an enzyme-linked immunosorbent assay (ELISA), and baPWV was measured using a volume plethysmographic device. Patients were divided into the PAS group (baPWV > 18.0 m/s) and the non-PAS group (baPWV ≤ 18.0 m/s). The associations of baPWV and other clinical and biochemical parameters with serum MDA-LDL were assessed by multivariable logistic regression analyses. A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of serum MDA-LDL for predicting PAS. Results: In multivariable logistic regression analysis, higher serum MDA-LDL, older age, and higher serum C-reactive protein [odds ratios (ORs) and 95% confidence intervals: 1.014 (1.004-1.025), 1.044 (1.004-1.085) and 3.697 (1.149-11.893)] were significantly associated with PAS. In the ROC curve analysis, the optimal cutoff value of MDA-LDL for predicting PAS was 80.91 mg/dL, with a sensitivity of 79.25% and a specificity of 59.57%. Conclusions: Greater serum MDA-LDL levels, particularly ≥80.91 mg/dL, were independently associated with PAS in HD patients. The findings suggest that oxidative stress plays a crucial role in the pathogenesis of PAS, and targeting MDA-LDL may be a potential therapeutic strategy for reducing cardiovascular risk in HD patients.

Serum Leptin Level is Positively Correlated with Aortic Stiffness in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The global number of people living with diabetes mellitus (DM) continues to grow. Obesity, smoking, hypercholesterolemia, and hypertension are independently correlated with the risk of cardiovascular disease (CVD) in diabetic patients regardless of differences in race or ethnicity. We aimed to investigate the relationship between serum leptin levels and aortic stiffness in patients with type 2 DM to identify cardiovascular risk at the early stage. METHODS: A total of 128 diabetic patients were enrolled after screening for eligibility at a medical center in Eastern Taiwan. Aortic stiffness was defined as having a carotid-femoral pulse wave velocity (cfPWV) of >10 m/s using applanation tonometry. Fasting serum levels of leptin and other associated biomarkers were determined by enzyme immunoassay or biochemical analyses. RESULTS: Forty-six diabetic patients with a cfPWV of >10 m/s were included in the aortic stiffness group. Compared with the control group (n = 82), our aortic stiffness group was significantly older (p = 0.019) and had higher body fat mass (p = 0.002), systolic blood pressure (SBP) (p < 0.001), serum triglyceride (p = 0.02), and serum leptin (p < 0.001). Aortic stiffness was also associated with insulin resistance (p = 0.026) and poorer blood sugar control (higher fasting glucose (p = 0.044) and glycated hemoglobin (HbA1c) (p = 0.049)). In the multivariable linear regression analyses examining the correlations between aortic stiffness and clinical variables, we found that age (ß = 0.291; p < 0.001), SBP (ß = 0.176; p = 0.033), logarithmically transformed urinary albumin-creatinine ratio (ß = 0.256; p = 0.002), and serum leptin levels (ß = 0.244; p = 0.002) were independently associated with cfPWV values. The analyses showed that only leptin was correlated with a higher probability of aortic stiffness (odds ratio: 1.055, 95% confidence interval: 1.005-1.107, p = 0.031). CONCLUSIONS: The results suggested that serum leptin is positively associated with aortic stiffness in patients with type 2 DM.

Association between Serum Soluble Urokinase-Type Plasminogen Activator Receptor Level and Arterial Stiffness in Chronic Hemodialysis Patients.

Cardiovascular diseases (CVDs) remain a significant cause of death in hemodialysis (HD) patients. To explore their associations, we examine the role of soluble urokinase-type plasminogen activator receptor (suPAR) in arterial stiffness in chronic HD patients. From June to August 2020, we recruited 135 chronic HD patients. The arterial stiffness group included patients with a carotid-femoral pulse-wave velocity (cfPWV) of >10 m/s. Fifty-five HD patients (40.7%) were in the arterial stiffness group. They had a higher prevalence of diabetes (p = 0.001) and hypertension (p = 0.039), were older (p = 0.007) and had higher aortic systolic blood pressure (p = 0.034), brachial systolic blood pressure (p = 0.025), glucose (p = 0.019), C-reactive protein (p = 0.039), and AIx75 (p = 0.003) and suPAR (p < 0.001) levels than the control group. After we performed multivariable logistic regression analysis, except age and glucose, serum suPAR (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.48-2.70, p < 0.001) was independently associated with arterial stiffness in chronic HD patients. In the multivariable linear regression analysis, suPAR positively correlated with cfPWV (ß = 0.475, p < 0.001) and could serve as a biomarker for arterial stiffness development in patients undergoing HD.

Localized periodontitis and kidney function for the risk of proteinuria in young adults in the CHIEF oral health study.

This study aimed to investigate the association of localized periodontitis with proteinuria in 1281 military young adults in Taiwan. Localized periodontitis was classified as Healthy/Stage I (N = 928) or Stage II/III (N = 353). Stage 2 chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of 60-89 mL/min/1.73 m2. Proteinuria was defined as protein levels of 2+ or 3+ on the dipstick test. Multiple logistic regression analysis with adjustments for age, sex, body mass index, remaining teeth number and other potential covariates were used to determine the association between localized Stage II/III periodontitis and dipstick proteinuria in patients with and without CKD. Localized stage II/III periodontitis was associated with a higher risk of dipstick proteinuria [odds ratio (OR) and 95% confidence interval: 1.89 (1.04-3.42)], but not with stage 2 CKD. However, the association between localized stage II/III periodontitis and dipstick proteinuria was observed only in patients with stage 2 CKD [OR: 3.80 (1.56-9.27)], while the association was null in participants without stage 2 CKD [OR: 1.02 (0.42-2.45)]. Our findings suggest that among young adults, especially those with a mildly impaired eGFR, localized periodontitis might contribute to acute or chronic kidney injury, which manifests as proteinuria.

Effects of Sacubitril/Valsartan Versus Telmisartan in Type 2 Diabetic or Pre-Diabetic Patients with Hypertension and Without Heart Failure: The Rationale and Design of A Randomized Clinical Trial.

BACKGROUND: Sacubitril/valsartan has revealed superior glycemic and blood pressure control compared with enalapril and irbesartan in patients with heart failure and type 2 diabetes and in individuals with chronic kidney disease. However, whether the effects of sacubitril/valsartan remain the same in those without heart failure is unknown. METHODS: A multicenter randomized double-blinded trial will be carried out in five military hospitals in Taiwan for a period of 1 year. Participants with prior cardiovascular diseases and heart failure will be excluded. The purpose of the study is to compare the effects of sacubitril/valsartan (97/103 mg once or twice daily) on the temporal changes in fasting blood glucose, HbA1c, insulin resistance and blood pressure levels with telmisartan (40 mg once or twice daily) in individuals with stage 1-3 hypertension and newly diagnosed type 2 diabetes or prediabetes who have an HbA1c ≥6.0% and a systolic blood pressure ≥130 mmHg or a diastolic blood pressure ≥85 mmHg. The inclusion criteria include the age of 35-70 years, women who are not pregnant, estimated glomerular filtration rate ≥45 ml/min per 1.73m2 and B-type natriuretic peptide levels <400 pg/ml. RESULTS: The sample size is estimated to be 502 participants for randomization according to an assumption of between-person standard deviation in systolic blood pressure of 15 mmHg or in HbA1c of 1.5%, which provides ≥80% power (at p =0.05) to detect a difference in systolic blood pressure of 4 mmHg or in HbA1c of 0.3% at the final follow-up. All participants will receive a comprehensive physical examination and tests for blood cell counts, blood biochemistry, urine analysis, 12-lead electrocardiography and an echocardiography every 3 months. CONCLUSION: All analyses will be performed based on the intention-to-treat principle among all randomized participants.

Hypoadiponectinemia is associated with aortic stiffness in nondialysis diabetic patients with stage 3-5 chronic kidney disease.

OBJECTIVES: Albuminuria and serum adiponectin levels are factors that have been associated with the development of cardiovascular disease in patients with diabetes mellitus. Here we investigated the relationship between serum adiponectin levels and aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. METHODS: Fasting blood samples were obtained from 80 nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry; cfPWV values of >10 m/s were defined as aortic stiffness. Serum adiponectin levels were determined by enzyme immunoassay. RESULTS: Forty-two patients (52.5%) with nondialysis diabetic kidney disease were diagnosed with aortic stiffness. The patients in this group were older (p = 0.011), had higher systolic blood pressure (p = 0.002) and urine albumin-to-creatinine ratios (p = 0.013), included fewer females (p = 0.024), and had lower serum adiponectin (p = 0.001) levels than those in the control group. Multivariable logistic regression analysis revealed that serum adiponectin was independently associated with aortic stiffness (odds ratio = 0.930, 95% confidence interval: 0.884-0.978, p = 0.005) and also positively correlated with cfPWV values by multivariable linear regression (ß = -0.309, p = 0.002) in nondialysis diabetic kidney disease patients. CONCLUSIONS: The results suggested that serum adiponectin levels could be used to predict aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease.

Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species.

Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß)). In the animal model, 14-week-old conscious Wistar-Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1ß in conscious rats.

Effects of Individualized Dietary Phosphate Control Program With a Smartphone Application in Hemodialysis Patients in Taiwan.

BACKGROUND: Hyperphosphatemia in end-stage renal disease patients is prevalent and associated with increasing cardiac mortality. Restricting dietary phosphate intake is a key element in controlling hyperphosphatemia, but most patients fail due to lack of knowledge and sustainability. In this study, we aimed to examine whether incorporating a smartphone application (APP) into a multidisciplinary caring system can decrease the prevalence of hyperphosphatemia in hemodialysis patients. METHODS: We designed a quasi-experimental study to enroll patients undergoing regular hemodialysis and assigned them to receive APP-assisted caring program (ACP group, n = 30) or standard education caring program (SCP group, n = 30). Both caring programs targeting dietary phosphate control were administered. Patients' general characteristics, self-care efficacy scales, knowledge test of phosphate control, and results of monthly blood biochemistry were analyzed. FINDINGS: Knowledge of diet phosphate control and self-care efficacy were significantly higher in the ACP group. Notably, the knowledge improvement was higher in patients aged over 60 years. Compared to the SCP group, the percentage of patients with successful hyperphosphatemia control was significantly higher in the ACP group (p = 0.0398). CONCLUSION: The APP-assisted caring program benefits patients with regular hemodialysis to achieve better dietary phosphate control without compromising proper protein intake.

Sex Differences in the Mortality Risk of Elderly Patients with Systolic Heart Failure in Taiwan.

BACKGROUND: Sex differences in heart failure mortality might be affected by age, race, and treatment response. Many large studies in Western countries have shown conflicting results, however few studies have been conducted in Asian patients. OBJECTIVES: We prospectively investigated the mortality risk in a multicenter cohort of 1,093 male and 416 female heart failure patients with reduced ejection fraction (HFrEF) hospitalized for worsening symptoms in Taiwan between 2013 and 2015. METHODS: Kaplan-Meier curve and Cox proportional regression analyses were used to determine the one-year mortality risk by sex. RESULTS: There were no significant differences in major adverse cardiovascular events, re-admission rate, and mortality between sexes in the overall cohort and the young subgroup during one-year of follow-up. In the elderly subgroup, the overall and cardiac mortality rate of the male patients were higher than those of the female patients (p = 0.035, p = 0.049, respectively). We found that the prognostic effect of old age on overall mortality rate appeared to be stronger in the male patients (p < 0.0001) than in the female patients (p = 0.69) in Cox regression analysis and Kaplan-Meier survival curves. Male sex was a risk factor for all-cause mortality in the elderly (hazard ratio: 1.50, 95% confidence interval 1.02-2.25) independently of systolic blood pressure, diabetes mellitus, hemoglobin concentration, kidney function, and medications. CONCLUSIONS: In the Taiwan HFrEF registry, the highest mortality risk was observed in male patients aged 65 years or more. Clinicians need to pay more attention to these patients.

Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells.

Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox's cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox's effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

Association of Single Measurement of dipstick proteinuria with physical performance of military males: the CHIEF study.

BACKGROUND: Proteinuria, a marker of kidney injury, may be related to skeletal muscle loss. Whether the severity of proteinuria is associated with physical performance is unclear. METHODS: We examined the association of proteinuria severity with physical performance cross-sectionally in 3357 military young males, free of chronic kidney disease, from the cardiorespiratory fitness and hospitalization events in armed Forces (CHIEF) study in Taiwan. The grades of proteinuria were classified according to one dipstick urinalysis which were collected at morning after an 8-h fast as unremarkable (0, +/-, and 1+), moderate (2+) and severe (3+ and 4+). Aerobic physical performance was evaluated by time for a 3000-m run and anaerobic physical performance was evaluated by numbers of 2-min sit-ups and 2-min push-ups, separately. Multiple linear regressions were used to determine the relationship. RESULTS: As compared with unremarkable proteinuria, moderate and severe proteinuria were dose-dependently correlated with 3000-m running time (ß: 4.74 (95% confidence intervals (CI): - 0.55, 10.02) and 7.63 (95% CI: 3.21, 12.05), respectively), and inversely with numbers of 2-min push-ups (ß = - 1.13 (- 1.97, - 0.29), and - 1.00 (- 1.71, - 0.28), respectively) with adjustments for age, service specialty, body mass index, blood pressure, alcohol intake, smoking, fasting plasma glucose, blood urea nitrogen, serum creatinine and physical activity. However, there was no association between proteinuria severity and 2-min sit-ups. CONCLUSIONS: Our findings show a relationship of dipstick proteinuria with aerobic physical performance and parts of anaerobic physical performance in military healthy males. This mechanism is not fully understood and requires further investigations.

Sex-specific association of hyperuricemia with cardiometabolic abnormalities in a military cohort: The CHIEF study.

Hyperuricemia has been associated with metabolic syndrome, and the association with various cardiometabolic risk factors may be affected by sex.We made a cross-sectional examination in a military cohort of 6738 men and 766 women, aged 18 to 50 years of Taiwan in 2013 to 2014. Hyperuricemia were defined as serum uric acid levels ≥7.0 mg/dL for men and ≥5.7 mg/dL for women, respectively. Multivariable logistic regression analyses were used to determine the associations between hyperuricemia and various metabolic abnormalities.In the overall population, hyperuricemia was associated with high blood pressure (odds ratio [OR]: 1.59, and 95% confidence intervals: 1.42-1.77), low high-density lipoprotein (OR: 1.75, 1.56-1.97), high triglycerides (OR: 2.14, 1.90-2.42), high low-density lipoprotein (OR: 1.71, 1.51-1.93), high fasting plasma glucose (OR: 1.29, 1.13-1.48), and central obesity (OR: 2.85, 2.55-3.18) after adjusting for age and serum creatinine concentrations. However, the associations with atherogenic lipid profiles including high triglycerides and high low-density lipoprotein were merely significant in men but not in women. In addition, there was a tendency for a sex difference in the association of hyperuricemia and raised blood pressure ≥130/85 mm Hg, which was greater in women than that in men (OR: 2.92, 1.37-6.25 and 1.54, 1.37-1.72, respectively; P for interaction = .059).Our findings suggest that the association between hyperuricemia and various cardiometabolic abnormalities in young adults may differ by sex, possibly due to a regulation of sex hormones and uneven effects of uric acid at the same levels between sexes on lipid metabolisms and arterial stiffness.

Therapeutic modification of arterial stiffness: An update and comprehensive review.

Arterial stiffness has been recognized as a marker of cardiovascular disease and associated with long-term worse clinical outcomes in several populations. Age, hypertension, smoking, and dyslipidemia, known as traditional vascular risk factors, as well as diabetes, obesity, and systemic inflammation lead to both atherosclerosis and arterial stiffness. Targeting multiple modifiable risk factors has become the main therapeutic strategy to improve arterial stiffness in patients at high cardiovascular risk. Additionally to life style modifications, long-term ω-3 fatty acids (fish oil) supplementation in diet may improve arterial stiffness in the population with hypertension or metabolic syndrome. Pharmacological treatment such as renin-angiotensin-aldosterone system antagonists, metformin, and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors were useful in individuals with hypertension and diabetes. In obese population with obstructive sleep apnea, weight reduction, aerobic exercise, and continuous positive airway pressure treatment may also improve arterial stiffness. In the populations with chronic inflammatory disease such as rheumatoid arthritis, a use of antibodies against tumor necrosis factor-alpha could work effectively. Other therapeutic options such as renal sympathetic nerve denervation for patients with resistant hypertension are investigated in many ongoing clinical trials. Therefore our comprehensive review provides knowledge in detail regarding many aspects of pathogenesis, measurement, and management of arterial stiffness in several populations, which would be helpful for physicians to make clinical decision.

Delayed high anion gap metabolic acidosis after a suicide attempt: case report.

BACKGROUND: Metabolic acidosis, especially when induced by multiple drug poisoning, often makes rapid and accurate differential diagnosis of the condition challenging. METHODS: We closely followed anion and osmolal gaps to differentiate among the aetiologies of metabolic acidosis caused by poisoning with unknown drugs. RESULTS: The patient was admitted to our emergency department (ED) in an alert and consciousness state after attempting suicide by ingestion of an uncertain quantity of rodenticides combined with an unknown liquid. Initially, metabolic acidosis (pH7.23) with normal anion gap (12.8) was observed. However, a change in consciousness and hypotension subsequently developed 6h later, combined with severe metabolic acidosis (pH7.16), high anion gap (25.5), and high osmolal gap (83). A presumed diagnosis of methanol intoxication was suspected. After 4h of high-flux haemodialysis (HD), the serum bicarbonate returned to 23 mmol/l, and the patient regained consciousness. The serum level of methanol before HD was 193.8 mg/dl. The patient was discharged nine days later without sequelae. CONCLUSIONS: Delayed high anion gap metabolic acidosis may occur in the ED. Frequent monitoring of anion and osmolal gaps is a feasible method to perform a rapid differential diagnosis, particularly in response to drug poisoning.

A hypokalaemic woman with nephrocalcinosis: rebirth of old knowledge.

The coexistence of hypokalaemia and nephrocalcinosis poses a challenge in rapid diagnosis and appropriate management. We describe a 38-year-old woman who presented with thirst, intermittent carpopedal spasm, paresthaesia of both hands and progressive weakness of lower extremities for two years. She had a history of chronic hypokalaemia of unknown cause with intermittent potassium supplementation for 7-8 y and bilateral nephrocalcinosis notable for one year. She denied vomiting, diarrhoea or use of laxatives, alcohol or diuretics. Her blood pressure was normal. Laboratory investigations showed hypokalaemia (2.7 mmol/L) and metabolic alkalosis (HCO3(-) 32.6 mmol/L, pH 7.46). Two random urine samples both showed a consistently high urine K(+) excretion but with excretion rates of Na(+), Cl(-) and divalent cations which were high in one sample but not the other. Ingestion of furosemide 120 mg daily for body image for 7-8 y was uncovered. With furosemide cessation and potassium supplementation, her hypokalaemia with neuromuscular symptoms was corrected but nephrocalcinosis persisted. Surreptitious use of diuretics for various purposes should be kept in mind as an important cause of hypokalaemia and/or nephrocalcinosis. Measurement of electrolyte concentrations in at least two random urine samples is warranted to distinguish it from true renal tubular disorders and extrarenal causes.