Phosphorus Content of Commonly Prescribed Medications Among Patients With Chronic Kidney Disease.

OBJECTIVES: This study aimed to build a brand-specific library of phosphorus content in medications and to determine the median daily phosphorus intake from medications among chronic kidney disease (CKD) patients in Singapore. METHODS: This is a single-center, cross-sectional study conducted in 200 patients with CKD Stages 3-5D. Package inserts of medications commonly used by the CKD patients were reviewed to identify brands containing phosphorus. Drug manufacturers were contacted to obtain phosphorus content of products. The median daily phosphorus intake from medications of the 200 patients was then calculated using the information. RESULTS: A total of 399 formulations of 204 medications and supplements were reviewed (March 2020). Fifty-eight (15%) formulations were found to contain phosphorus. Forty-three (11%) formulations had missing information regarding the phosphorus content. Based on available information, the median daily phosphorus intake from medications was 1.28 mg (interquartile range = 0.006-16.08) across the CKD stages. Patients with CKD Stage 5D had a higher median intake of 4.09 mg (P = .009). A dose-independent variation in phosphorus content of excipients between generic and branded formulations was noted in this study. We have developed a library of phosphorus content in medications. CONCLUSIONS: The inorganic phosphorous content in frequently prescribed medications for CKD patients is generally low, with excipients (as opposed to the active ingredient or counterions) being the main source of phosphorus. Although this may seem almost negligible in comparison to the recommended dietary intake, prescribers should still exercise care, given the wide range of phosphorus content possible between different brands of the same medication, and the unpredictable absorption of inorganic phosphate in CKD patients.

The impact of axial spondyloarthritis on quality of life (QoL): a comparison with the impact of moderate to end-stage chronic kidney disease on QoL.

PURPOSE: The purpose of the study was to assess the impact of axial spondyloarthritis (axSpA) on patients' quality of life (QoL) compared to patients with moderate to end-stage chronic kidney disease (CKD). METHODS: We conducted secondary analysis of QoL data obtained from patients with axSpA and CKD from 2011 to 2014. QoL was assessed using the SF-36 version 2 and KDQoL-SF for patients with axSpA and CKD, respectively. Patients with CKD were subcategorized to CKD-pre-dialysis, hemodialysis (CKD-HD) and peritoneal dialysis (CKD-PD). Linear regression was used to compare QoL between patients with axSpA and CKD after adjusting for age, gender, ethnicity, education level, and marital status. RESULTS: A total of 765 patients (mean age 54.6, 63.0% males, 69.0% Chinese) were analyzed, of which 188 (24.5%) had axSpA. Patients with axSpA had poorer SF-36 bodily pain (BP) scores (axSpA: reference; CKD-pre-dialysis ß: 11.04, p < 0.001; CKD-HD ß: 9.52, p < 0.001; CKD-PD ß: 10.35, p < 0.001) and higher general health scores (axSpA: reference; CKD-pre-dialysis ß: - 7.87, p < 0.001; CKD-HD ß: - 7.14, p < 0.001, CKD-PD ß: - 7.25, p < 0.001) as compared to patients with CKD. Generally, patients with axSpA had poorer SF-36 scores than patients with CKD-pre-dialysis and similar SF-36 scores compared to patients with CKD-HD or CKD-PD. CONCLUSIONS: The burden of axSpA on QoL is not trivial and is comparable to patients with CKD-HD or CKD-PD.

Association of anemia and mineral and bone disorder with health-related quality of life in Asian pre-dialysis patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor health-related quality of life (HRQoL). The association of CKD-related complications such as anemia and mineral and bone disorders (MBD) with HRQoL in pre-dialysis patients is not well-studied. As such, this study aimed to determine the association of anemia and MBD with HRQoL in pre-dialysis patients. METHODS: This was a cross-sectional study involving 311 adult pre-dialysis patients with stage 3-5 CKD from an acute-care hospital in Singapore. Patients' HRQoL were assessed using Kidney Disease Quality of Life Short Form (KDQOL-SF™) and EuroQol 5 Dimensions-3 levels (EQ5D-3L). HRQoL between patients with and without anemia or MBD were compared by separate hierarchical multiple linear regression analyses using various HRQoL scales as dependent variables, adjusted for sociodemographic, clinical and psychosocial variables. RESULTS: After adjusting for MBD, anemia was associated with lower HRQoL scores on work status (WS), physical functioning (PF) and role physical [ß (SE): -10.9 (4.18), p = 0.010; -3.0 (1.28), p = 0.018; and -4.2 (1.40), p = 0.003, respectively]. However, significance was lost after adjustments for sociodemographic variables. Patients with MBD had poorer HRQoL with respect to burden of kidney disease, WS, PF and general health [(ß (SE): -7.9 (3.88), p = 0.042; -9.5 (3.99), p = 0.018; -3.0 (1.22) p = 0.014; -3.6 (1.48), p = 0.015, respectively]. Although these remained significant after adjusting for sociodemographic variables, significance was lost after adjusting for clinical variables, particularly pill burden. This is of clinical importance due to the high pill burden of CKD patients, especially from medications for the management of multiple comorbidities such as cardiovascular and mineral and bone diseases. CONCLUSIONS: Neither anemia nor MBD was associated with HRQoL in our pre-dialysis patients. Instead, higher total daily pill burden was associated with worse HRQoL. Medication reconciliation should therefore be routinely performed by clinicians and pharmacists to reduce total daily pill burden where possible.

Vitamin D status and its association with mineral and bone disorder in a multi-ethnic chronic kidney disease population.

BACKGROUND: Vitamin D deficiency is associated with secondary hyperparathyroidism and mineral and bone disorder (MBD) in chronic kidney disease (CKD). This study aimed to determine the prevalence of vitamin D insufficiency/deficiency, and the association between vitamin D status and MBD in a multi-ethnic CKD population in Southeast Asia. METHODS: Predialysis CKD patients were included in this cross-sectional study. Patient demographics, medical/medication histories, and laboratory parameters (serum 25-hydroxyvitamin D (25(OH)D), creatinine, phosphate (P), calcium, albumin, and intact-PTH (i-PTH)) were collected and compared among patients with various CKD stages. The association between 25(OH)D and these parameters was determined by multiple linear regression. RESULTS: A total of 196 patients with mean ± SD eGFR of 26.4 ± 11.2 mL/min/1.73 m2 was included. Vitamin D deficiency (25(OH)D concentration < 15 ng/mL) and insufficiency (25(OH)D concentration 16 - 30 ng/mL) was found in 29.1% and 57.7% of the patients, respectively. Mean ± SD serum 25(OH)D was 20.8 ± 9.3 ng/mL. Female patients had lower vitamin D concentrations than males (16.9 ng/mL vs. 23.9 ng/mL; p < 0.001). Vitamin D levels were also higher in Chinese (22.3 ng/mL) than Malay (17.3 ng/mL) and Indian (13.1 ng/mL) patients (p < 0.05). Nonadjusted analyses showed higher i-PTH concentration in vitamin D deficient patients (p < 0.05). CONCLUSION: Despite being a sun-rich country all year round, the majority (86.8%) of predialysis CKD patients in Singapore have suboptimal vitamin D status. Lower vitamin D concentrations were found in females and in those with darker skin tone. Vitamin D deficient patients also tended to have higher i-PTH levels.

Prevalence and outcomes associated with hypocalcaemia and hypercalcaemia among pre-dialysis chronic kidney disease patients with mineral and bone disorder.

Introduction: Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients. Methods: A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca2+) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca2+: between 1.90 and 2.10 mmol/L) and 'severe' (Ca2+: <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca2+: between 2.47 and 3.00 mmol/L), moderate (Ca2+: between 3.01 and 3.50 mmol/L) and severe (Ca2+: >3.50 mmol/L). Results: Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality (P > 0.05) or the occurrence of cardiovascular events (P > 0.05). Conclusion: Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes.

Prevalence of chronic kidney disease-mineral and bone disorder in incident peritoneal dialysis patients and its association with short-term outcomes.

INTRODUCTION: A complex relationship exists between chronic kidney disease-mineral and bone disorder (CKD-MBD) and adverse outcomes among dialysis patients. This study aimed to report the prevalence of CKD-MBD and examine the impact of achieving target CKD-MBD parameters on morbidity and mortality one year after peritoneal dialysis (PD) initiation. METHODS: In this retrospective cohort study, patients electively initiated on PD were followed up for one year. Laboratory parameters were collected and the prevalence of CKD-MBD 4-6 months after PD initiation was determined based on the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Linear regression and Cox proportional hazards model were used to evaluate the effects of achieving CKD-MBD targets 4-6 months after PD initiation on hospitalisation, the incidence of peritonitis or exit-site infections (ESIs), and mortality at one year. RESULTS: The prevalence of CKD-MBD among the 86 patients in this study was 86.0% (KDOQI) and 54.7% (KDIGO). There was no significant difference in hospitalisation duration between patients who achieved targets and those who did not. Patients who failed to meet all the KDIGO CKD-MBD or calcium serum targets had a higher incidence of peritonitis or ESI. A trend toward shorter time to death was observed among patients who failed to meet the KDIGO phosphorus serum targets. CONCLUSION: There was moderate (KDIGO) to high prevalence (KDOQI) of CKD-MBD among the patients. Achievement of all the KDIGO CKD-MBD or calcium serum targets was associated with reduced peritonitis or ESI, while achievement of the KDIGO phosphorus serum targets was associated with improved survival.

Predictors of anemia in a multi-ethnic chronic kidney disease population: a case-control study.

Anemia is a common complication of chronic kidney disease (CKD). However, risk factors of anemia in CKD patients in Singapore are not well established. Hence, a retrospective, case-control study involving non-dialysis CKD patients was conducted to determine possible predictors of anemia in the local CKD population. Non-dialysis adult CKD patients, not receiving renal replacement therapy or erythropoiesis-stimulating-agents were included. Parameters collected included demographics e.g. age, sex and race; clinical data e.g. CKD stage and medical/medication histories; and laboratory data e.g. serum electrolytes, urinary and hematologic parameters. Patients were classified as anemic or non-anemic using a threshold hemoglobin level of 10 g/dL. The parameters were evaluated for their predictive value for anemia development using multivariate logistical regression and calculation of odds ratios. Statistical analyses were performed using STATA. A total of 457 patients (162 anemic and 295 non-anemic) were analysed. Multivariate analysis showed that probability of developing anemia was greater for patients with stage 5 CKD (OR 16.76, p < 0.001), with hematological disorders (OR 18.61, p < 0.001) and with respiratory disorders (OR 4.54, p = 0.004). The probability of developing anemia was lower for patients with higher previous hemoglobin concentration (OR 0.32, p < 0.001) and in those receiving iron supplements (OR 0.44, p = 0.031). Gender and race were not found to be significant predictors of anemia. Risk of anemia is increased in patients with advanced CKD, haematological disorders, respiratory disorders, and those not taking iron supplements. This study has increased our understanding of the patient subgroups at risk for anemia.

Malnutrition in patients undergoing hemodialysis: is intradialytic parenteral nutrition the answer?

Patients with end-stage renal disease often experience malnutrition as a result of decreased dietary intake; inadequate dialysis; loss of nutrients into the dialysate; abnormal protein, carbohydrate, and lipid metabolism; and concomitant diseases, which may contribute to an increase in morbidity and mortality. Intradialytic parenteral nutrition (IDPN) is being used to improve nutritional status, in conjunction with other methods of nutritional supplementation. The biggest advantage of IDPN is probably its convenience since it is administered during dialysis treatment and thus does not require additional clinic visits or prolonged dialysis time. Although IDPN has several disadvantages, its ability to improve nutritional status and reduce morbidity and mortality in patients with end-stage renal disease is promising. Well-designed, large-scale, prospective studies are required to confirm its beneficial effects.

Clinical and demographic predictors for vitamin D deficiency in multiethnic Asian patients with chronic kidney disease.

BACKGROUND: Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and can cause skeletal and extraskeletal complications. The purpose of this study is to determine the clinical and demographic risk factors for vitamin D deficiency in multiethnic CKD patients in Singapore, a sun-rich country, so that patients at risk can be identified and treated early. METHODS: Pre-dialysis CKD patients from the National University Hospital (NUH), Singapore, Outpatient Renal Clinic who had their serum 25-hydroxyvitamin D [25(OH)D] levels measured between January 2008 and October 2010 were included. Their clinical and demographic parameters were collected from hospital databases and medical charts. Logistic regression was used to identify potential predictors for vitamin D deficiency in these patients. Two models, Mt30 and Mt16, were built using threshold serum 25(OH)D levels of ≤30 and <16 ng/mL, respectively. RESULTS: Of the 219 patients included, 82.7 and 25.6% had serum 25(OH)D levels ≤30 and <16 ng/mL, respectively. Predictors identified for vitamin D deficiency include absence of vitamin D supplementation, type 2 diabetes mellitus (DM), non-cancer diagnosis, younger age, Malay race, treatment with calcitriol and higher serum bicarbonate (CO2) levels. Common predictors for the two models were lack of vitamin D supplementation and DM. The areas under the receiver-operating characteristic (ROC) curve for the validation sets were 0.697 and 0.687 for the Mt30 and Mt16 models, respectively. CONCLUSIONS: Vitamin D deficiency is common among multiethnic CKD patients in Singapore. Risk factors identified in this study include absence of vitamin D supplementation, DM, non-cancer diagnosis, young age, Malay race, calcitriol treatment and higher serum CO2. The knowledge of these risk factors is useful for predicting vitamin D deficiency in CKD patients in Singapore.

Phosphate-binding efficacy of crushed vs. chewed lanthanum carbonate in hemodialysis patients.

Lanthanum carbonate, a chewable noncalcium-containing phosphorus (P) binder, is useful for treating secondary hyperparathyroidism in patients who have hypercalcemia and cannot swallow whole tablets. However, some patients cannot chew tablets or prefer to crush and mix them with food. This study was conducted to determine the P-binding efficacy of crushed lanthanum and compare it with chewed lanthanum in hemodialysis (HD) patients. After a 1-week washout period, 11 hemodialysis patients (7 men, 4 women) were randomized to receive, in a crossover fashion, lanthanum 1000 mg 3 times daily chewed with meals and lanthanum 1000 mg 3 times daily crushed into a fine powder, mixed with applesauce and taken with meals, for 4 weeks each. Serum P was measured at the end of each washout (baseline) and weekly during treatment. Changes in serum P from baseline for crushed lanthanum were compared with chewed lanthanum using paired sample t test. Administration of crushed lanthanum resulted in a significant reduction in serum P from baseline (P reduction [mg/dL] for crushed lanthanum in week 1: 2.1 ± 0.4, week 2: 1.7 ± 0.5, week 3: 1.7 ± 0.5, week 4: 1.7 ± 0.4, P<0.05). No statistically significant differences were observed in serum P reduction from baseline and serum P attained during treatment with crushed when compared with chewed lanthanum. Crushed lanthanum is effective in reducing serum P and have similar P-binding efficacy to chewed lanthanum. Crushing lanthanum and mixing it with food can thus be an option for patients who are unable to chew or swallow whole tablets.

Effects of lanthanum carbonate on the absorption and oral bioavailability of ciprofloxacin.

BACKGROUND AND OBJECTIVES: Phosphate binders such as calcium salts or sevelamer, a cationic polymer, can markedly reduce absorption of oral ciprofloxacin. This randomized, open-label, two-way, crossover study examined the influence of the cation lanthanum on systemic ciprofloxacin exposure after oral administration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twelve patients randomly received in a crossover manner a single oral dose of ciprofloxacin 750 mg alone and plus lanthanum carbonate 1 g three times daily with meals for six doses, with a washout interval of 7 to 14 d. Serial blood and urine samples were collected for 24 h after ciprofloxacin administration, and ciprofloxacin concentrations were determined using reverse-phase HPLC. Pharmacokinetic parameters of ciprofloxacin were calculated by noncompartmental methods, and the effect of lanthanum on ciprofloxacin pharmacokinetic parameters was assessed using ANOVA. RESULTS: Lanthanum decreased (P < 0.001) the mean ciprofloxacin area under the plasma concentration-time curve by 54% and the maximum plasma concentration by 56%. The 24-h urinary recovery of ciprofloxacin was reduced by 52% by lanthanum (P < 0.001). No statistically significant differences in ciprofloxacin time to maximum plasma concentration, elimination half-life, and renal clearance occurred between the two arms. CONCLUSIONS: Lanthanum carbonate significantly reduces the systemic exposure to orally administered ciprofloxacin. Concomitant administration of both drugs should be avoided to prevent possible suboptimal response to ciprofloxacin.