Biomedical subjects

Khashayar Sakhaee

Publications and source records attributed to Khashayar Sakhaee.

23 records · Page 2Linked to original sources

PubMed2002

Pathophysiology of uric acid nephrolithiasis.

Humans although a predominantly ureotylic organism, has preserved the ability to excrete nitrogen as uric acid and ammonia. An imbalance between these two secondary modes of nitrogen excretion has resulted in uric acid precipitation in human urine. Uric acid nephrolithiasis can arise from diverse etiologies all with distinct underlying defects converging to one or more of three defects of hyperuricosuria, acidic urine pH, and low urinary volume, originating from secondary, genetic or heretofore undefined (idiopathic) causes. A subset of idiopathic uric acid nephrolithiasis (gouty diathesis) may be the "tip of the icebergp" of a broader systemic illness characterized by insulin resistance. A novel renal manifestation of insulin resistance is a mild defect in ammonium excretion, which is not severe enough to disturb acid-base homeostasis, but is sufficient to set up the chemical milieu for uric acid nephrolithiasis.

Humans↗

PubMed2002

Pathophysiologic basis for normouricosuric uric acid nephrolithiasis.

BACKGROUND: Low urinary pH is the commonest and by far the most important factor in uric acid nephrolithiasis but the reason(s) for this defect is (are) unknown. Patients with uric acid nephrolithaisis have normal acid-base parameters according conventional clinical tests. METHODS: We studied steady-state plasma and urinary parameters of acid-base balance in subjects with normouricosuric pure uric acid stones. We also tested the ability of these subjects to excrete ammonium in response to an acute acid load. We compared these parameters in patients with pure uric acid stones to patients with mixed uric acid/calcium oxalate stones, pure calcium stones, and normal volunteers. RESULTS: Pure uric acid stone formers have a much higher incidence of either diabetes or glucose intolerance. After equilibration to a control diet, patients with uric acid stones have lower urinary pH and they excrete less of their acid as ammonium. This is compensated by higher titratable acidity and hypocitraturia. Despite their low baseline urinary pH, uric acid stone formers further acidify their urine after an acid load because of a severely impaired ammonia excretory response. Their characteristics are significantly different from normal volunteers and pure calcium stone formers. Patients with mixed uric acid/calcium stones exhibit intermediate characteristics. CONCLUSION: We propose that certain patients with normouricosuric uric acid nephrolithiasis have a renal acidification disease. The primary defect lies in renal ammonium excretion, which may be linked to the insulin-resistant state. Although net acid excretion is maintained at the expense of increased titratable acidity and to some degree hypocitraturia, the compromise is acid urine pH and may result in uric acid nephrolithiasis.

Adult↗

PubMed2002

Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism.

BACKGROUND: Low-carbohydrate high-protein (LCHP) diets are used commonly for weight reduction. This study explores the relationship between such diets and acid-base balance, kidney-stone risk, and calcium and bone metabolism. METHODS: Ten healthy subjects participated in a metabolic study. Subjects initially consumed their usual non-weight-reducing diet, then a severely carbohydrate-restricted induction diet for 2 weeks, followed by a moderately carbohydrate-restricted maintenance diet for 4 weeks. RESULTS: Urine pH decreased from 6.09 (Usual) to 5.56 (Induction; P < 0.01) to 5.67 (Maintenance;P < 0.05). Net acid excretion increased by 56 mEq/d (Induction; P < 0.001) and 51 mEq/d (Maintenance; P < 0.001) from a baseline of 61 mEq/d. Urinary citrate levels decreased from 763 mg/d (3.98 mmol/d) to 449 mg/d (2.34 mmol/d; P < 0.01) to 581 mg/d (3.03 mmol/d; P < 0.05). Urinary saturation of undissociated uric acid increased more than twofold. Urinary calcium levels increased from 160 mg/d (3.99 mmol/d) to 258 mg/d (6.44 mmol/d; P < 0.001) to 248 mg/d (6.19 mmol/d; P < 0.01). This increase in urinary calcium levels was not compensated by a commensurate increase in fractional intestinal calcium absorption. Therefore, estimated calcium balance decreased by 130 mg/d (3.24 mmol/d; P < 0.001) and 90 mg/d (2.25 mmol/d; P < 0.05). Urinary deoxypyridinoline and N-telopeptide levels trended upward, whereas serum osteocalcin concentrations decreased significantly (P < 0.01). CONCLUSION: Consumption of an LCHP diet for 6 weeks delivers a marked acid load to the kidney, increases the risk for stone formation, decreases estimated calcium balance, and may increase the risk for bone loss.

Acid-Base Imbalance↗

PubMed2002

Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy.

The adipocyte-derived hormone leptin, which plays an important role in energy homeostasis, has been suggested to have an influence on bone development and remodeling. However, it is not clear from animal studies whether leptin is a stimulator or an inhibitor of bone growth. Cross-sectional studies in humans suggest that serum leptin levels are positively associated with bone mineral density (BMD), but these observations are not consistent, and whether this relationship is independent of obesity remains unclear. We therefore examined the effect of sc leptin administration on BMD and markers of bone turnover in two women, one with congenital generalized lipodystrophy and the other with acquired generalized lipodystrophy. Both patients had regular menstrual cycles. At baseline, the BMD for both patients, measured at the lumbar spine and total hip, was within 1 SD of the peak bone mass. There was no significant change in BMD in both patients after 16-18 months of leptin therapy. Similarly, concentrations of serum osteocalcin and bone-specific alkaline phosphatase or urinary excretion of deoxypyridinoline and N-telopeptides remained unchanged after 6-8 months of leptin therapy, suggesting no effects of leptin on osteoblastic or osteoclastic activity. Our preliminary data suggest that sc leptin replacement in hypoleptinemic patients with generalized lipodystrophy has no effect on the mature adult skeleton.

Absorptiometry, Photon↗

PubMedDate not supplied

Bisphosphonate-induced hypocalcemia: report of 3 cases and review of literature.

OBJECTIVE: To report 3 cases of bisphosphonate-induced hypocalcemia and review the relevant literature. METHODS: We present the clinical and laboratory findings in 3 cases of bisphosphonate-induced hypocalcemia, and discuss the pathophysiologic mechanisms and the pertinent literature. RESULTS: In our first patient (case 1), symptomatic hypocalcemia developed after intravenous administration of pamidronate for management of multiple myeloma. He had vitamin D insufficiency and impaired renal function at the time of pamidronate therapy. Our second patient (case 2) presented with symptomatic hypocalcemia 12 weeks after initiation of alendronate therapy for osteoporosis. Her serum 25-hydroxyvitamin D level was low (3 ng/mL), attributable to a combination of poor vitamin D intake, limited exposure to sunlight, use of phenytoin, and previous intestinal resections. In our third patient (case 3), hypocalcemia developed on 2 different occasions, each episode occurring after intravenous administration of pamidronate for hypercalcemia of malignancy. All 3 patients had underlying conditions that impaired the homeostatic response to bisphosphonates and contributed to the severe hypocalcemia. Review of published reports on symptomatic bisphosphonate-induced hypocalcemia disclosed that hypocalcemia develops in patients with unrecognized hypoparathyroidism, impaired renal function, or vitamin D deficiency. Overall, the rate of the development of hypocalcemia was related to the potency of the bisphosphonate administered. CONCLUSION: The increasing use of bisphosphonates and the introduction of more potent agents impose a considerable risk for bisphosphonate-induced hypocalcemia in a substantial number of patients. Greater awareness of this complication, a better understanding of the underlying mechanisms, and proper assessment of patients in whom bisphosphonate therapy is contemplated should reduce the frequency of occurrence of this potentially life-threatening complication.

Aged↗