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1.
BMC Nephrol ; 22(1): 244, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215201

RESUMO

BACKGROUND: Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of "single starting calcium infusion rate for all patients" puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. METHODS: This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA "Non-shock" protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. RESULTS: Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th-75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91-2.13). CONCLUSIONS: The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of "one starting dose for all" reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.


Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Ácido Cítrico/administração & dosagem , Ácido Cítrico/farmacocinética , Protocolos Clínicos , Terapia de Substituição Renal Contínua/instrumentação , Terapia de Substituição Renal Contínua/métodos , Fígado/metabolismo , Idoso , Terapia de Substituição Renal Contínua/efeitos adversos , Cuidados Críticos , Feminino , Humanos , Rins Artificiais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Soluções
2.
Kidney360 ; 2(2): 192-204, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35373034

RESUMO

Background: Regional citrate anticoagulation (RCA) is not recommended in patients with shock or severe liver failure. We designed a protocol with personalized precalculated flow settings for patients with absent citrate metabolism that abrogates risk of citrate toxicity, and maintains neutral continuous KRT (CKRT) circuit calcium mass balance and normal systemic ionized calcium levels. Methods: A single-center prospective cohort study of patients in five adult intensive care units triaged to the CVVHDF-RCA "Shock" protocol. Results: Of 31 patients included in the study, 30 (97%) had AKI, 16 (52%) had acute liver failure, and five (16%) had cirrhosis at the start of CKRT. The median lactate was 5 mmol/L (interquartile range [IQR], 3.2-10.7), AST 822 U/L (IQR, 122-2950), ALT 352 U/L (IQR, 41-2238), total bilirubin 2.7 mg/dl (IQR, 1.0-5.1), and INR two (IQR, 1.5-2.6). The median first hemofilter life censored for causes other than clotting exceeded 70 hours. The cumulative incidence of hypernatremia (Na >148 mM), metabolic alkalosis (HCO3- >30 mM), and hypophosphatemia (P<2 mg/dl) were one out of 26 (4%), zero out of 30 (0%), and one out of 30 (3%), respectively, and were not clinically significant. Mild hypocalcemia occurred in the first 4 hours in two out of 31 patients, and corrected by hour 6 with no additional Ca supplementation beyond the per-protocol administered Ca infusion. The maximum systemic total Ca (tCa; mM)/ionized Ca (iCa; mM) ratio never exceeded 2.5. Conclusions: The Shock protocol can be used without contraindications and is effective in maintaining circuit patency with a high, fixed ACDA infusion rate to blood flow ratio. Keeping single-pass citrate extraction on the dialyzer >0.75 minimizes the risk of citrate toxicity even in patients with absent citrate metabolism. Precalculated, personalized dosing of the initial Ca-infusion rate from a table on the basis of the patient's albumin level and the filter effluent flow rate maintains neutral CKRT circuit calcium mass balance and a normal systemic iCa level.


Assuntos
Anticoagulantes , Ácido Cítrico , Adulto , Anticoagulantes/efeitos adversos , Coagulação Sanguínea , Ácido Cítrico/uso terapêutico , Humanos , Estudos Prospectivos , Diálise Renal/métodos
3.
Kidney Int ; 61(5): 1739-49, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11967023

RESUMO

BACKGROUND: Sulfonylurea agents exert their physiological effects in many cell types via binding to specific sulfonylurea receptors (SUR). SUR couple to inwardly-rectifying K+ channel (Kir6.x) to form tetradimeric ATP-sensitive K+ channels (KATP). The SUR subunits confer ATP-sensitivity on KATP and also provide the binding sites for sulfonylureas and other pharmacological agents. Our previous work demonstrated that the exposure of mesangial cells (MC) to sulfonylureas generated profound effects on MC glucose uptake and matrix metabolism and induced heightened cell contractility in association with Ca2+ transients. Because these responses likely resulted from the binding of sulfonylurea to a mesangial SUR2, we subsequently documented [3H]-glibenclamide binding to MC and the gene expression of several mesangial SUR2 transcripts. From these data, we inferred that MC expressed the components of a mesangial KATP and sought to establish their presence in primary MC. METHODS: To obtain mesangial SUR2 cDNA sequences, rapid amplification of cDNA ends (RACE) was utilized. DNA sequences were established by the fluorescent dye termination method. Gene expression of mesangial SUR2 and Kir6.1/2 was examined by reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis. SUR2 proteins were identified by immunoblotting of mesangial proteins from membrane-enriched fractions with polyclonal antiserum directed against SUR2. RESULTS: RACE cloning yielded two mesangial SUR2 cDNAs of 4.8 and 6.7 kbp whose open reading frames translated proteins of 964 and 1535 aa, respectively. Using probes specific to each cDNA, the presence of a unique, 5.5 kbp serum-regulated mesangial SUR2 splice variant was established. The sequence of this mesangial SUR2 (mcSUR2B) shares identity with the recently cloned rat SUR2B (rSUR2B), but, in comparison to rSUR2B, is truncated by 12 exons at the N-terminus where it contains a unique insert of 16 aa. Immunoblotting studies with anti-SUR2 antiserum demonstrated SUR2 proteins of 108 and 170 kD in membrane-enriched fractions of MC protein extracts. Complementary studies showed abundant gene expression of Kir6.1, thereby establishing gene expression of both components of KATP. CONCLUSIONS: Based upon analogy to vascular smooth muscle cells (VSMC), there are at least two putative mesangial KATP that most likely represent hetero-octamers, comprised of either rSUR2B or mcSUR2 in complex with Kir6.1. Our results define the mesangial SUR2B as the possible first link in a chain of cellular events that culminates in MC contraction and altered extracellular matrix metabolism following exposure to sulfonylureas. In addition, our results serve as the basis for the future elucidation of the electrophysiologic characteristics of the mesangial KATP and the study of endogenous regulators of mesangial cell contractility.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Mesângio Glomerular/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio/genética , Receptores de Droga/genética , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Clonagem Molecular , DNA Complementar , Expressão Gênica/fisiologia , Mesângio Glomerular/química , Mesângio Glomerular/citologia , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Canais de Potássio/química , Estrutura Terciária de Proteína , Ratos , Ratos Wistar , Receptores de Droga/química , Transdução de Sinais/fisiologia , Receptores de Sulfonilureias
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