Magnesium and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.

Mastitis is associated with increased free fatty acids, somatic cell count, and interleukin-8 concentrations in human milk.

BACKGROUND: Research in bovine lactation has demonstrated that milk produced by a mammary gland displaying inflammation-based symptoms of mastitis has increased levels of free fatty acids (FFAs) compared with milk produced by a contralateral asymptomatic gland. However, the effects of mastitis on lipid classes in milk have not been investigated in humans. METHODS: The study described here compared milk collected from the symptomatic breast of women with mastitis (n=14) with that collected from the contralateral asymptomatic breast to determine if mastitis caused alterations in the quantity of total lipids, FFAs, and phospholipids (PLs), as well as the fatty acid profiles of these lipid classes. To assess their efficacy as biomarkers of mastitis, samples were also analyzed for selected markers of local inflammation: sodium, somatic cell count (SCC), and interleukin-8 (IL-8). RESULTS: FFAs were higher in milk from the mastitic breast compared with that from the healthy breast (1.31 vs. 1.07 ± 0.10 g/100 g of lipid, p<0.05). Similarly, SCC and IL-8 were elevated roughly 10-fold in milk from mastitic breasts, compared with milk from healthy breasts, and sodium tended to be higher in milk from mastitic breasts (p<0.10). However, there were no differences in total lipid, PLs, or fatty acid profiles within each lipid class. CONCLUSIONS: In summary, mastitis is associated with increased lipolysis in the human breast but not alterations in milk fat synthesis, as evidenced by a lack of alteration in total milk lipids. Additionally, these results indicate that SCC and IL-8 may be better indicators of mammary inflammation than sodium content.

Risk factors and consequences of hyperaluminemia in a peritoneal dialysis cohort.

BACKGROUND: Widespread Al toxicity is unusual today. In 2005, Canadian peritoneal dialysis (PD) centers reported widespread hyperaluminemia in patients using dialysates from one specific manufacturer. Our objectives were to evaluate risk factors related to Al accumulation and to assess its clinical consequences in patients from 2 centers. METHODS: A retrospective closed cohort study was conducted in patients treated with PD in May 2005. A multivariate linear regression model was constructed to identify variables associated with a higher serum Al level in the exposed group at the moment of solution change. Using appropriate statistical methods, anemia and bone metabolism parameters were compared between the exposed and unexposed groups. Time to first peritonitis was estimated by the Kaplan-Meier method. RESULTS: The study cohort included 87 Al-exposed patients and 95 unexposed patients. In the exposed group, serum Al at the moment of solution change was influenced by the length of exposure to Al-containing dialysates and by PD creatinine clearance; serum Al was inversely correlated with renal creatinine clearance. No consequences of Al accumulation were observed. No difference was observed in the time to first peritonitis between patients who switched manufacturers and those who remained with the original manufacturer. CONCLUSIONS: Our results suggest that hyperaluminemia is directly related to the length and extent of exposure to Al-containing dialysates; residual renal function is protective against Al accumulation. Because the problem was detected rapidly, no clinical consequences of hyperaluminemia were observed in the study cohort.

Variability in CKD stage in outpatients followed in two large renal clinics.

OBJECTIVE: Chronic kidney disease (CKD) is staged by glomerular filtration rate (GFR). CKD stages sometimes vary between routine office visits, and it is unknown if this impacts renal and patient survival separately from a cross-sectional CKD stage value. We quantified and categorized CKD stage variability in a large group of outpatients and correlated this with clinical and demographic features and with renal and patient survival. METHODS: All estimated GFRs were staged in the first observation period. CKD stages were then categorized as static, improving, worsening, or fluctuating. Logistic regression analysis was performed to identify clinical variables associated with CKD stage variability. Death and dialysis progression rates were then collected and analyzed using Cox proportional regression. RESULTS: During a 1.1-year observation period, 1,262 patients (mean age 71.25 years) had a mean 5 eGFR's. CKD stages were static in 60.4%, worsened in 14.4%, improved in 7.4%, and fluctuated in 17.2% of patients. Secondary analysis revealed heavy proteinuria and East Asian ethnicity to be negatively, and diabetes mellitus and previous acute kidney injury to be positively associated with improving CKD stages. Cox proportional regression of 902 patients analyzed 2.3 years later revealed a negative association with improving CKD stage and subsequent need for dialysis. CONCLUSIONS: CKD stage changed in 40% of 1,262 elderly patients when determined 5 times in just over 1 year. Improving CKD stage was the only variability pattern significantly associated with any of the clinical outcomes when assessed 2.3 years later, being unlikely to be linked with subsequent need for dialysis.

Aluminum toxicokinetics in peritoneal dialysis patients.

CONTEXT: Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition. METHODS: Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion. RESULTS: After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues. CONCLUSION: This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.

Use of PTFE stent grafts for hemodialysis-related central venous occlusions: intermediate-term results.

PURPOSE: To assess the safety and effectiveness of a polytetrafluoroethylene (PTFE) encapsulated nitinol stents (Bard Peripheral Vascular, Tempe, AZ) for treatment of hemodialysis-related central venous occlusions. MATERIALS AND METHODS: Study design was a single-center nonrandomized retrospective cohort of patients from May 2004 to August 2009 for a total of 64 months. There were 14 patients (mean age 60 years, range 50-83 years; 13 male, 1 female). All patients had autogenous fistulas. All 14 patients had central venous occlusions and presented with clinical symptoms of the following: extremity swelling (14%, 2 of 14), extremity and face swelling (72%, 10 of 14), and face swelling/edema (14%, 2 of 14). There was evidence of access dysfunction with decreased access flow in 36% (5 of 14) patients. There were prior interventions or previous line placement at the site of the central venous lesion in all 14 patients. Results were assessed by recurrence of clinical symptoms and function of the access circuit (National Kidney Foundation recommended criteria). RESULTS: Sixteen consecutive straight stent grafts were implanted in 14 patients. Average treated lesion length was 5.0 cm (range, 0.9-7 cm). All 14 patients had complete central venous occlusion (100% stenosis). The central venous occlusions were located as follows: right subclavian and brachiocephalic vein (21%, 3 of 14), right brachiocephalic vein (36%, 5 of 14), left brachiocephalic vein (36%, 5 of 14), and bilateral brachiocephalic vein (7%, 1 of 14). A total of 16 PTFE stent grafts were placed. Ten- or 12-mm-diameter PTFE stent grafts were placed. The average stent length was 6.1 cm (range, 4-8 cm). Technical (deployment), anatomic (<30% residual stenosis), clinical (resolution of symptoms), and hemodynamic (resolution of access dysfunction) success were 100%. At 3, 6, and 9 months, primary patency of the treated area and access circuit were 100% (14 of 14). CONCLUSIONS: This PTFE encapsulated stent graft demonstrates encouraging intermediate-term patency results for central vein occlusions. Further prospective studies with long-term assessment and larger patient populations will be required.

Peritoneal dialysis in the nursing home.

UNLABELLED: The mean age of patients with end-stage renal disease increases steadily. The elderly on dialysis have significant comorbidity and require extra attention to meet their dialysis, dietary, and social needs, and some may need to be treated at a long-term care facility such as a nursing home (NH). Providing dialysis and caring for elderly patients in a nursing home (NH) presents a number of challenges. Few data are available in the literature about elderly patients on peritoneal dialysis (PD) in an NH. This paper describes our experience of starting and maintaining a peritoneal dialysis program in three community-based nursing homes. RESULTS: During the period 2004-2008, after the nursing home personnel had received appropriate training, we established a PD program in three community-based nursing homes and admitted 38 patients on peritoneal dialysis. We educated 112 NH staff over the three-year period. Mean age of the patients at entry was 77.3 + or - 8.5(18.4%) were male. The main causes of end-stage renal disease were diabetes mellitus (DM) 21 (55.8%) and hypertension 13 (34.2%). Comorbid conditions included DM (27, 71.1%), hypertension (26, 68.4%), coronary artery disease (18.5%), chronic heart failure (11, 28.9%), cerebrovascular event (12, 31.6%), and cancer(3, 7.9%). The average total time on chronic peritoneal dialysis was 36.5 + or - 29.8 months, (median 31, range: 1-110 months) of which the average time in the NH program, as of the time of this report, was 18.4 + or - 13.1 months (median 15.5, range: 1-45 months). During the study period, 16 (42.1%) of the patients died, 2 (5.3%) transferred to HD, 2 (5.3%) stopped treatment, and 18 (47.4%) are still in the program. Actuarial patient survival from entry into the NH program was 89.5% at six months, 60.5% at 12 months, 39.5% at 24 months and 13.2% at 36 months. Patient survival from initiation of chronic dialysis was 89.5% at six months, 76.3% at 12 months, 63.1% at 24 months, and 39.5% at 36 months. We observed 28 episodes of peritonitis with a rate of one episode every 40.3 treatment-months. Two PD catheters had to be replaced, giving a rate of one in every 362.5 patient months. CONCLUSION: Our results with elderly patients in a nursing home show an excellent patient and technique survival and a low peritonitis rate. With appropriate training of the NH nursing staff, peritoneal dialysis could be performed successfully in these nursing homes. Successful peritoneal dialysis in a nursing home requires a close collaboration between the nursing home staff and PD dialysis unit.

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic.

BACKGROUND: The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR). PATIENTS AND METHODS: Between September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89 ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min-1/1.73/m2-1/year-1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than -5 ml/min/year); (2) mildly progressive slope (>-5 to -1 to +1 to or=+5). RESULTS: At the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90-60 ml/m), 46.7% on CKD stage 3 (eGFR: 59-30 ml/m), and 47.5% on CKD stage 4 (eGFR: 29-15 ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (P<0.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance. CONCLUSION: Referral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.

Generalized seizure and toxic epidermal necrolysis following levofloxacin exposure.

OBJECTIVE: To report the case of a ciprofloxacin-allergic patient who developed a generalized tonic-clonic seizure and toxic epidermal necrolysis (TEN) following a single dose of levofloxacin. CASE SUMMARY: An 87-year-old white woman was admitted to the hospital following a transient episode of unresponsiveness that had been accompanied by flailing of her limbs. Approximately 4 hours earlier, she had developed a pruritic rash on her trunk and limbs, and 3 hours before this had taken a first dose of levofloxacin. The fluoroquinolone had been prescribed for treatment of an upper respiratory tract infection. She had developed a skin rash approximately 3 years earlier following ciprofloxacin prescribed for a urinary tract infection. On admission, the patient had a normal neurologic examination. She was mildly hypomagnesemic (serum magnesium 1.7 mg/dL), with no other electrolyte imbalances present. Skin biopsy confirmed TEN. The lesions progressed to involve 30% of the body surface area and were managed with polymyxin B and gramicidin cream. Levofloxacin was discontinued on admission, and no anticonvulsants were prescribed. The woman remained seizure-free at discharge one week later. DISCUSSION: Generalized tonic-clonic seizures are a rare complication of levofloxacin therapy. TEN following levofloxacin use has, to our knowledge, as of March 28, 2005, been previously reported only once. The seizure and TEN were probably induced by levofloxacin as corroborated by the Naranjo probability scale. We believe that the previous adverse dermatologic reaction to ciprofloxacin sensitized our patient to levofloxacin. CONCLUSIONS: These rare adverse reactions to levofloxacin, involving disparate organ systems, can occur simultaneously. A previous dematologic adverse reaction to a fluoroquinolone can sensitize a patient to more severe adverse reactions (with onset after only a single dose of the subsequent fluoroquinolone). Further fluoroquinolone use should be avoided in such patients.

A cross-sectional immunosurveillance study of anti-EPO antibody levels in CRF patients receiving epoetin alfa in 5 Ontario Renal Centers.

BACKGROUND: Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted. METHODS: More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay. RESULTS: Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies. CONCLUSION: Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.