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Biomedical subjects

J Gitomer

Publications and source records attributed to J Gitomer.

3 recordsLinked to original sources

Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation.

BACKGROUND: Citrate anticoagulation is commonly used for continuous venovenous hemodialysis (CVVHD) to minimize the risk of bleeding complications. We have previously reported a liver failure patient undergoing citrate-based CVVHD with elevated serum total to ionized calcium ratio. Diminished liver metabolism of citrate with resultant elevated systemic citrate was thought to be the cause. METHODS: To determine the incidence and clinical significance of an elevated total to ionized calcium ratio during citrate-based CVVHD, 161 patients undergoing citrate-based CVVHD were screened for the presence of an elevated total to ionized calcium ratio (the subset with increased total to ionized calcium ratio comprised the study group). Because all patients in the study group had liver failure, two control groups of patients with normal total to ionized calcium ratios were formed-those without liver failure (control I) and those with liver failure (control II). RESULTS: An elevated total to ionized calcium ratio was detected in 12% of all patients. Thirty-three percent of liver failure patients demonstrated an elevated total to ionized calcium ratio. The study group demonstrated significantly higher mean total calcium levels, significantly lower mean ionized calcium levels, and significantly higher mean total to ionized calcium ratios than controls. As a result, the study group also had significantly increased mean calcium chloride replacement requirements in comparison with controls. The mean calcium to citrate infusion ratio was elevated in the study group in comparison with controls. An elevated total to ionized calcium ratio was associated with increased mortality in comparison with controls. No patients suffered complications from ionized hypocalcemia or elevated serum total calcium. CONCLUSIONS: Systemic citrate accumulation as evidenced by an elevated total to ionized calcium ratio occurs commonly in patients requiring CVVHD using citrate-based regional anticoagulation. Observing changes in the total to ionized calcium ratio can aid in early detection of patients with hepatic failure who are unable to appropriately metabolize citrate and will require calcium chloride infusion rates significantly above normal.

Adult↗

Frequency, potential risk and therapeutic intervention in end-stage renal disease patients with antiphospholipid antibody syndrome: a multicenter study.

BACKGROUND: Antiphospholipid antibody syndrome (APAS) is characterized by the presence of anticardiolipin antibodies (ACA) in association with thrombotic disorders of arterial and/or venus systems, spontaneous abortion(s) or thrombocytopenia. METHODS: In this multicenter study, 502 end-stage renal disease (ESRD) patients awaiting renal transplants were screened to determine the frequency of APAS, the potential risk associated with APAS, and strategies for therapeutic intervention. Ninety-three patients (19%) had high titers of ACA. Twenty-three patients had documented evidence of one or more of the thrombotic disorders such as lupus, frequent abortions, frequent thrombosis of arteriovenous shunts, biopsy-proven microrenal angiopathy, or thrombocytopenia and thus were diagnosed with APAS. Of these 23 patients, 11 received kidney transplants either with (4 patients) or without (7 patients), concomitant anticoagulation therapy. RESULTS: All seven of the patients with APAS not treated with anticoagulation therapy lost their allografts within 1 week as a result of renal thrombosis. In contrast, three out of four transplant patients with APAS treated with anticoagulation therapy maintained their allografts for over 2 years. The fourth patient lost his graft within a week because of thrombosis. Of the remaining 70 patients with high titers of ACA but no evidence of thrombotic disorders, 37 received kidney transplants. None lost their allografts as a result of thrombosis. Our data suggest that, although 19% of our ESRD patients exhibit high titer of ACA, only 5% of the patients have APAS. CONCLUSION: In conclusion, our data suggest that the patients with APAS are at high risk of posttransplant renal thrombosis. Anticoagulation therapy could prevent patients from posttransplant thrombosis in patients with APAS.

Antibodies, Anticardiolipin↗

H+,K+-ATPase.

The H+,K+-ATPases comprise a group of integral membrane proteins that belong to the X+,K+-ATPase subfamily of P-type cation-transporting ATPases. Although these H+,K+-ATPase isoforms share approximately 60-70% amino acid identity, they exhibit discrete kinetic and pharmacological properties when expressed in heterologous systems. HK alpha2 has been categorized by its insensitivity to Sch-28080, an inhibitor of the gastric H+,K+-ATPase, and partial sensitivity to ouabain, an inhibitor of the Na+,K+-ATPase. This functional profile contrasts with the pharmacological sensitivities ascribed to HK alpha2 in transport studies in rat isolated medullary collecting ducts perfused in vitro and in mouse medullary collecting duct cell lines. HK alpha2 mRNA and protein abundance appears to be both tissue and site-specifically upregulated in response to chronic hypokalemia. This regulatory response has been localized to the outer and inner medulla. To reconcile these expressed sensitivities to those reported in vitro in isolated tubules and cells in culture, it would be necessary to invoke modification of the pharmacologic insensitivity of the colonic H+,K+-ATPase to Sch-28080. Although a 'unique' beta-subunit has been reported recently, this beta-subunit (beta(c)) is identical at the amino acid level to the recently cloned beta3-Na+,K+-ATPase. Moreover, while HK alpha2 can assemble indiscriminately with any X+,K+-ATPase beta-subunit, HK alpha2 has been reported to assemble stably with beta1-Na+,K+-ATPase in the renal medulla and in the distal colon. It remains conceivable that subunit assembly could be tissue specific and might respond to different physiological and pathophysiological stimuli. Furthermore, recent studies have suggested that the H+,K+-ATPase is both Na+-dependent and localized to the apical membrane in the distal colon. Therefore, future studies will need to resolve these discrepancies by determining if a unique, yet undiscovered H+,K+-ATPase isoform exists in kidney, or if post-translational modifications of the alpha- and/or beta-subunits could account for these functional diversities.

Animals↗