Kidney Function

Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing.Study Design: Randomized parallel open-label study.Setting & Participants: Hemodialysis patients.Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets.Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels.Measurements: Serum phosphorus to 24 weeks.Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder–treated patients and 64% of sevelamer hydrochloride tablet–treated patients had serum phosphorus levels within the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate–treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder–treated patients discontinued treatment because of these treatment-related events or consent withdrawal.Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted.Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.

A 64-year-old man with a 15-year history of poorly controlled type 2 diabetes and a 10-year history of hypertension and hyperlipidemia had developed multiple diabetes-related complications within the last 5 years. He first developed albuminuria 5 years ago, and during the next several years, he experienced a fairly rapid decrease in kidney function, with an estimated glomerular filtration rate of 55 mL/min/1.73 m2 noted 2 years ago. Proliferative retinopathy was diagnosed 5 years ago, and he underwent laser photocoagulation. Four years ago, he noted symptoms of peripheral neuropathy manifested as shooting pain and numbness with loss of light touch, thermal, and vibratory sensation in a stocking distribution. Last year, he developed a nonhealing ulcer on the plantar aspect of his left foot that was complicated by gangrene and resulted in a below-the-knee amputation of the left leg 1 year ago. He now reports new onset of weakness, lightheadedness, and dizziness on standing that affects his daily activities. He reports lancinating pain in his right lower extremity, worse in the evening. Medications include neutral protamine Hagedorn insulin twice daily and regular insulin on a sliding scale; metoprolol, 50 mg/d; lisinopril, 40 mg/d; atorvastatin, 80 mg/d; furosemide, 40 mg/d; and aspirin, 81 mg/d. Blood pressure is 127/69 mm Hg with a pulse rate of 96 beats/min while supine and 94/50 mm Hg with a pulse rate of 102 beats/min while standing. Strength is normal, but with complete loss of all sensory modalities to the knee in his remaining limb and up to the wrists in both upper extremities, and he is areflexic. Today’s laboratory evaluations show a serum creatinine level of 2.8 mg/dL, estimated glomerular filtration rate of 24 mL/min/1.73 m2, hemoglobin A1c level of 7.9%, and urine protein excretion of 2.1 g/1 g of creatinine. What would be the most appropriate management for this patient?

Background: The relationship between kidney function and bone loss is unclear.Study Design: A prospective observational study.Setting & Participants: 191 men and 444 women aged ≥ 50 years participating in a population-based observational study designed to determine risk factors for bone loss and fractures.Predictors: The primary predictor of change in bone mineral density (BMD) was estimated creatinine clearance (using the Cockcroft-Gault formula) measured at baseline and stratified by quartiles. Our secondary predictor was estimated glomerular filtration rate using the Modification of Diet in Renal Disease Study equation, also stratified by quartiles.Outcomes & Measurements: Changes in BMD at the lumbar spine, total hip, and femoral neck during 5 years.Results: Compared with participants in the first quartile of estimated creatinine clearance (>101.2 mL/min), those in remaining quartiles were older (quartile 1, 50.0 years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3 mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed less; reported more sedentary hours; were less likely to report excellent, very good, or good self-reported health; consumed less caffeine; and had lower serum calcium and phosphate and higher serum parathyroid hormone levels. After adjusting for age, weight, sex, baseline BMD, and these differences, compared with those in the first quartile, those in the fourth quartile had decreases in BMD of 0.08 g/cm2 (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm2 (95% CI, 0.06-0.1) at the femoral neck, and 0.09 g/cm2 (95% CI, 0.07-0.1) at the total hip. Bone loss did not increase with worsening kidney function (P for trend > 0.05). Results were not substantially different using estimated glomerular filtration rate.Limitations: Observational study design and indirect measures of kidney function.Conclusions: Men and women with impaired kidney function are at increased risk of bone loss, even with minimal reduction in kidney function.