Aaron Halabe

Uric acid nephrolithiasis.

Uric acid is the end-product of purine nucleotide metabolism in man. The renal handling of urate is a complicated process, resulting in a fractional clearance of 8.2-10.3%. The anhydrous form is thermodynamically the most stable uric acid crystal. Uric acid is a weak acid that ionizes with a Pka at pH 5.75. At the normal acidic region, uric acid solubility is strongly increased by urinary pH. The prevalence of uric acid stones varies between countries, reflecting climatic, dietary, and ethnical differences, ranging from 2.1% (in Texas) to 37.7% (in Iran). The risk for uric acid stone formation correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. Hyperuricosuria is the major risk factor, the most common cause being increased purine intake in the diet. Acquired and hereditary diseases accompanied by hyperuricosuria and stone disease include: gout, in strong correlation with the amount of uric acid excreted, myelo- and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia and hemolytic disorders, hemoglobinopathies and thalassemia, the complete or partial deficiency of HGPRT, superactivity of PRPP synthetase, and hereditary renal hypouricemia. A common denominator in patients with idiopathic and gouty stone formers is a low urinary pH. Uric acid nephrolithiasis is indicated in the presence of a radiolucent stone, a persistent undue urine acidity and uric acid crystals in fresh urine samples. A radiolucent stone in combination with normal or acidic pH should raise the possibility of urate stones.(ABSTRACT TRUNCATED AT 250 WORDS)

Low HDL levels and the risk of death, sepsis and malignancy

AbstractBackgroundHigh density lipoprotein (HDL) plays an important role as an anti-atherogenic molecule, but also possesses anti-inflammatory and anti-angiogenic properties. The effect of extremely low levels of HDL on the risk of sepsis and malignancy were therefore examined.MethodsA retrospective analysis of patients hospitalized at the Edith Wolfson Medical center was conducted. Patients were divided into Group 1: 108 patients with serum HDL levels ≤20 mg/dl. Group 2: 96 patients with serum HDL levels ≥65 mg/dl. Medical history and laboratory data was recorded. ResultsThe mean HDL levels in Group 1 were 16.1 ± 33 mg/dl compared to 74.9 ± 12.6 mg/dl in Group 2. Using a multivariate logistic regression analysis, low HDL was inversely associated with death (OR 0.96, 95% 0.93–0.99, P = 0.02), 3.98 fold increase in odds of fever (OR 3.98, 95% CI 1.3–11.8, P = 0.01), and 6.7-fold increase in the risk of cancer (OR 6.68, 95% CI 1.8–24.5, P = 0.004). HDL serum levels were inversely associated with sepsis. For each 1 mg/dl increase in HDL, a relative 11% decrease in odds of sepsis was observed (OR 0.886, 95% CI 0.8–0.976, P = 0.01).ConclusionsExtremely low serum HDL levels (≤20 mg/dl) are associated with an increased risk of death, sepsis and malignancy.

Hypoparathyroidism—a long-term follow-up experience with 1α-vitamin D3 therapy

OBJECTIVE Previous studies have suggested that alpha‐D3 therapy can cause deterioration in renal function. We have, therefore, examined the long‐term effect of 1α‐hydroxyvitamin D3 (alpha‐D3) administration upon renal function in hypoparathyroid patients.

Effect of parathyroid adenoma excision on interleukin-6 (IL-6) and IL-2 receptor levels.

1,25-Dihydroxycholecalciferol [1,25(OH)2D], besides its role in calcium and phosphorus homeostasis, is also an important immunoregulatory molecule. Plasma levels of this hormone may be normal or elevated in patients with primary hyperparathyroidism. 1,25(OH)2D has been reported to inhibit production of the cytokines interleukin-2 (IL-2) and IL-6. In the present study, we examined the effect of parathyroid adenoma excision on serum IL-2 receptor (IL-2R) levels and the release and production of IL-2R and IL-6 by peripheral blood lymphocytes (each measurement was performed twice). Ten patients (5 females and 5 males aged 45 to 78 years) with primary hyperparathyroidism were enrolled in the study. The diagnosis of primary hyperparathyroidism was based on the presence of asymptomatic hypercalcemia, hypophosphatemia, and elevated serum intact PTH levels. Three weeks after removal of the parathyroid adenoma, there was a significant increase in the serum level of IL-2R, as well as the PHA-stimulated peripheral blood lymphocyte production of IL-6 and release of IL-2R. The results indicate that the removal of a parathyroid adenoma in patients with primary hyperparathyroidism causes a significant increase in IL-2R and IL-6 levels. The mechanism by which hyperparathyroidism may affect these cytokines and how they seem related to the levels of vitamin D is discussed.

Serum Urate and Renal Urate Clearance in Parathyroid Disorders

Hyperuricemia has been reported in a substantial proportion of patients with hyperparathyroidism (hyperPT) and with hypoparathyroidism (hypoPT) (1). The mechanism of the hyperuricemia in both parathyroid disorders has not conclusively been clarified. In both parathyroid abnormalities the hyperuricemia was postulated to reflect decreased renal urate clearance, attributed in hyperPT to a transitory renal tubular damage (2) and in hypoPT to a tubular abnormality associated with the decreased renal phosphate clearance (3). The present study was undertaken in order to assess the prevalence of hyperuricemia in the parathyroid disorders and in order to improve our knowledge of the renal urate handling in the various states of parathyroid pathology.

Juvenile Gout and Hyperuricosuria Due to Chronic Compensated Hemolytic Syndrome

In recent years it has become evident that the proportion of purine overproduces among the gouty population is smaller than was previously estimated (1). In addition, the reason for purine overproduction in most of the overproducing patients is still unknown. Only in a limited number could a hereditary enzymatic defect be proved (2). Recently we found a patient with juvenile gout due to chronic compensated (nonanemic) intracorpuscular hemolysis. In a subsequent study of our gouty patients suspected of being overproducers (urinary urate excretion on a regular home diet > 900 mg/24 h), an additional 7 patients, representing a substantial proportion of all our purine-over-producing gouty patients, were found with evidence suggesting the presence of chronic compensated hemolysis. It thus appears that chronic compensated hemolysis may be a relatively common cause of metabolic gout.