RESUMO
Acidemia is one of the risk factors for end-stage kidney disease and increases the mortality rate of patients with chronic kidney disease (CKD). Although urinary ammonium (U-NH4 + ) is the crucial component of renal acid excretion, U-NH4 + concentration is not routinely measured. To estimate U-NH4 + , urine osmolal gap (UOG = urine osmolality - [2(Na+ + K+ ) + urea + glucose]) is calculated and the formula (U-NH4 + = UOG/2) has traditionally been used. However, the usefulness of this formula is controversial in CKD patients. We assessed the relationship between U-NH4 + and UOG in patients with CKD. Blood and spot urine samples were collected in 36 patients who had non-dialysis-dependent CKD. The mean ± SD age of patients was 72.0 ± 14.8 years, and the mean ± SD serum creatinine and U-NH4 + were 2.7 ± 2.3 mg/dl and 9.3 ± 9.2 mmol/L, respectively. A significant relationship was found between UOG/2 and U-NH4 + (r = .925, p < .0001). U-NH4 + estimated using the UOG was on average higher by 4.7 mmol/L than the measured one. Our results suggested that UOG could be a useful tool in clinical settings, especially in patients with moderate to severe CKD.
Assuntos
Equilíbrio Ácido-Base , Acidose/urina , Amônia/urina , Insuficiência Renal Crônica/urina , Acidose/diagnóstico , Acidose/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Concentração Osmolar , Valor Preditivo dos Testes , Eliminação Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Índice de Gravidade de Doença , UrináliseRESUMO
The factors contributing to increased morbidity and mortality in SARS-CoV-2 infection are diverse, and include diabetes, obesity, Chronic Obstructive Pulmonary Disease (COPD), advanced age, and male sex. Although there is no obvious connection between these, they do have one common denominator-they all have a tendency towards lower urine pH, which may indicate a lower-than-normal tissue pH. Furthermore, it has been shown that lower pH has two important negative influences: 1) it enhances viral fusion via the endosomal route, thereby facilitating viral multiplication; and 2) it facilitates increased production of inflammatory cytokines, thereby exacerbating the cytokine storm. This paper discusses published literature on lower tissue/interstitial pH in those diseases/co-morbidities that are known risk factors of severe COVID-19, and hypothesize that small doses of baking soda could be a simple, cost-effective, and rapid method of reducing both morbidity and mortality in COVID-19 patients.
Assuntos
Acidose/metabolismo , COVID-19/metabolismo , Citocinas/metabolismo , Diabetes Mellitus/metabolismo , Obesidade/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Internalização do Vírus , Acidose/tratamento farmacológico , Acidose/urina , Fatores Etários , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/urina , Intervenção Médica Precoce , Humanos , Concentração de Íons de Hidrogênio , Obesidade/epidemiologia , Obesidade/urina , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/urina , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Fatores Sexuais , Bicarbonato de Sódio/uso terapêutico , Urina/químicaRESUMO
INTRODUCTION: The kidneys play a central role in eliminating metabolic waste products and drugs through transporter-mediated excretion along the proximal tubule. This task is mostly achieved through a variety of transporters from the solute carrier family 22 (SLC22) family of organic cation and anion transporters. Metabolic acidosis modulates metabolic and renal functions and also affects the clearance of metabolites and drugs from the body. We had previously shown that induction of metabolic acidosis in mice alters a large set of transcripts, among them also many transporters including transporters from the Slc22 family. OBJECTIVE: Here we further investigated the impact of acidosis on Slc22 family members. METHODS: Metabolic acidosis was induced for 2 or 7 days with NH4Cl, some animals also received the uricase inhibitor oxonic acid for comparison. Expression of transporters was studied by qPCR and immunoblotting. RESULTS: NH4Cl induced no significant changes in plasma or urine uric acid levels but caused downregulation of Slc22a1 (Oct1), Slc22a6 (Oat1), Slc22a19 (Oat5), and -Slc22a12 (Urat1) at mRNA level. In contrast, Slc22a4 mRNA (Octn1) was upregulated. On protein level, NH4Cl increased Octn1 (after 7 days) and Urat1 (after 2 days) abundance and decreased Oat1 (after 2 days) and Urat1 (after 7 days). Oxonic acid had no impact on protein abundance of any of the transporters tested. CONCLUSION: In summary, metabolic acidosis alters expression of several transporters involved in renal excretion of metabolic waste products and drugs. This may have implications for drug kinetics and clearance of waste metabolites.
Assuntos
Acidose/metabolismo , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/biossíntese , Nefropatias/patologia , Acidose/sangue , Acidose/patologia , Acidose/urina , Animais , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/genética , Proteínas da Membrana Plasmática de Transporte de Catecolaminas/metabolismo , Nefropatias/sangue , Nefropatias/metabolismo , Nefropatias/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 1 de Transcrição de Octâmero/biossíntese , Fator 1 de Transcrição de Octâmero/genética , Fator 1 de Transcrição de Octâmero/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácido Úrico/sangue , Ácido Úrico/urinaRESUMO
BACKGROUND AND OBJECTIVES: Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration. RESULTS: Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity. CONCLUSIONS: Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3.
Assuntos
Acidose/etiologia , Compostos de Amônio/urina , Anemia Falciforme/complicações , Capacidade de Concentração Renal , Túbulos Renais/fisiopatologia , Eliminação Renal , Acidose/diagnóstico , Acidose/fisiopatologia , Acidose/urina , Adulto , Anemia Falciforme/diagnóstico , Feminino , Fludrocortisona/administração & dosagem , Furosemida/administração & dosagem , Taxa de Filtração Glomerular , Humanos , Concentração de Íons de Hidrogênio , Testes de Função Renal , Túbulos Renais/metabolismo , Masculino , Concentração Osmolar , Estudos Prospectivos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Urina/química , Adulto JovemRESUMO
BACKGROUND: Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHS) deficiency is an autosomal recessive inborn error of metabolism, which will give rise to failure of ketogenesis in liver during illness or fasting. It is a very rare disease with only a few patients reported worldwide, most of which had a good prognosis after proper therapies. CASE PRESENTATION: We report a 9-month-old boy with mHS deficiency presenting with unusually severe and persistent acidosis after diarrhea and reduced oral food intake. The metabolic acidosis persisted even after supplementation with sugar and alkaline solution. Blood purification and assisted respiration alleviated symptoms, but a second onset induced by respiratory infection several days later led to multiple organ failure and death. Urine organic acid analysis during the acute episode revealed a complex pattern of ketogenic dicarboxylic and 3-hydroxydicarboxylic aciduria with prominent elevation of glutaric acid and adipic acid, which seem to be specific to mHS deficiency. Plasma acylcarnitine analysis revealed elevated 3-hydroxybutyrylcarnitine and acetylcarnitine. This is the first report of elevated 3-hydroxybutyrylcarnitine in mHS deficiency. Whole exome sequencing revealed a novel compound heterozygous mutation in HMGCS2 (c.100C > T and c.1465delA). CONCLUSION: This severe case suggests the need for patients with mHS deficiency to avoid recurrent illness because it can induce severe metabolic crisis, possibly leading to death. Such patients may also require special treatment, such as blood purification. Urine organic acid profile during the acute episode may give a hint to the disease.
Assuntos
Acidose/genética , Acil Coenzima A/deficiência , Hidroximetilglutaril-CoA Sintase/genética , Mitocôndrias/enzimologia , Mutação/genética , Acidose/terapia , Acidose/urina , Adipatos/urina , Carnitina/análogos & derivados , Carnitina/sangue , Carnitina/urina , Diarreia/complicações , Ácidos Dicarboxílicos/urina , Evolução Fatal , Mutação da Fase de Leitura/genética , Glutaratos/urina , Humanos , Lactente , Masculino , Insuficiência de Múltiplos Órgãos/complicações , Infecções Respiratórias/complicações , Sequenciamento do ExomaAssuntos
Acetil-CoA C-Aciltransferase/deficiência , Acidose , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Corpos Cetônicos/sangue , Vômito , Acetoacetatos/urina , Acetil-CoA C-Aciltransferase/sangue , Acetil-CoA C-Aciltransferase/urina , Acidose/sangue , Acidose/complicações , Acidose/urina , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/urina , Glicina/análogos & derivados , Glicina/urina , Humanos , Hidroxibutiratos/urina , Lactente , Masculino , Vômito/sangue , Vômito/etiologia , Vômito/urinaRESUMO
Renal ammonia excretion is a critical component of acid-base homeostasis, and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the present study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-mo-old C57BL/6 mice. Ammonia excretion, which was less in male mice under basal conditions, increased in response to acid loading to a greater extent in male mice, such that maximal ammonia excretion did not differ between the sexes. Fundamental structural sex differences in the nonacid-loaded kidney persisted after acid loading, with less cortical proximal tubule volume density in the female kidney than in the male kidney, whereas collecting duct volume density was greater in the female kidney. To further investigate sex-dependent differences in the response to acid loading, we examined the expression of proteins involved in ammonia metabolism. The change in expression of phosphoenolpyruvate carboxykinase and Rh family B glycoprotein with acid loading was greater in male mice than in female mice, whereas Na+-K+-2Cl- cotransporter and inner stripe of the outer medulla intercalated cell Rh family C glycoprotein expression were significantly greater in female mice than in male mice. There was no significant sex difference in glutamine synthetase, Na+/H+ exchanger isoform 3, or electrogenic Na+-bicarbonate cotransporter 1 variant A protein expression in response to acid loading. We conclude that substantial sex-dependent differences in the renal ammonia response to acid loading enable a similar maximum ammonia excretion response.
Assuntos
Acidose/urina , Amônia/urina , Rim/metabolismo , Acidose/patologia , Animais , Proteínas de Transporte/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Feminino , Ácido Clorídrico/farmacologia , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Medula Renal/metabolismo , Medula Renal/patologia , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Caracteres SexuaisRESUMO
We have recently reported that type A intercalated cells of the collecting duct secrete Na+ by a mechanism coupling the basolateral type 1 Na+-K+-2Cl- cotransporter with apical type 2 H+-K+-ATPase (HKA2) functioning under its Na+/K+ exchange mode. The first aim of the present study was to evaluate whether this secretory pathway is a target of atrial natriuretic peptide (ANP). Despite hyperaldosteronemia, metabolic acidosis is not associated with Na+ retention. The second aim of the present study was to evaluate whether ANP-induced stimulation of Na+ secretion by type A intercalated cells might account for mineralocorticoid escape during metabolic acidosis. In Xenopus oocytes expressing HKA2, cGMP, the second messenger of ANP, increased the membrane expression, activity, and Na+-transporting rate of HKA2. Feeding mice with a NH4Cl-enriched diet increased urinary excretion of aldosterone and induced a transient Na+ retention that reversed within 3 days. At that time, expression of ANP mRNA in the collecting duct and urinary excretion of cGMP were increased. Reversion of Na+ retention was prevented by treatment with an inhibitor of ANP receptors and was absent in HKA2-null mice. In conclusion, paracrine stimulation of HKA2 by ANP is responsible for the escape of the Na+-retaining effect of aldosterone during metabolic acidosis.
Assuntos
Equilíbrio Ácido-Base , Acidose/enzimologia , Fator Natriurético Atrial/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Túbulos Renais Coletores/enzimologia , Sódio/urina , Acidose/genética , Acidose/fisiopatologia , Acidose/urina , Adaptação Fisiológica , Aldosterona/urina , Animais , GMP Cíclico/urina , Feminino , ATPase Trocadora de Hidrogênio-Potássio/deficiência , ATPase Trocadora de Hidrogênio-Potássio/genética , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos C57BL , Camundongos Knockout , Comunicação Parácrina , Ratos , Transdução de Sinais , Xenopus laevisAssuntos
Acetaminofen/efeitos adversos , Acidose/induzido quimicamente , Analgésicos não Narcóticos/efeitos adversos , Ácido Pirrolidonocarboxílico/urina , Acetaminofen/uso terapêutico , Acidose/terapia , Acidose/urina , Idoso , Analgésicos não Narcóticos/uso terapêutico , Humanos , Masculino , Manejo da DorRESUMO
5-oxoprolinemia (pyroglutamic acid, PGA) in the absence of acetaminophen use has been rarely reported as a cause for high anion gap metabolic acidosis. We investigated the prevalence and risk factors for elevated PGA concentrations among hospitalized patients with high anion gap metabolic acidosis: We prospectively enrolled patients with high anion gap metabolic acidosis hospitalized in the department of medicine. For each patient we collected the main diagnosis, concurrent medications and laboratory parameters. Spot urine samples were tested for PGA concentration. Levels ≥63 µmol/mmol creatinine were considered elevated. Overall, forty patients were prospectively followed. Mean age was 66.9 (17.9) years. Four (6.3%) patients had a high urine PGA level and demonstrated also lower blood pH (7.2 vs 7.3, p = 0.05) and lower serum lactate concentration (17.5 mg/dl vs 23.0 mg/dl, p = 0.04). Additionally, the high PGA level group consisted of more patients with septic shock [2/4 (50%) vs 3/36 (8.3%)] with a trend towards significance (p = 0.07). In conclusion, PGA might have a role in patients with septic shock and acidosis. Being a treatable condition, PGA should be taken into consideration particularly when no other cause for high anion gap is identified.
Assuntos
Equilíbrio Ácido-Base , Acidose/metabolismo , Ácido Pirrolidonocarboxílico/metabolismo , Acidose/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Pirrolidonocarboxílico/urinaRESUMO
Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; however, current methods to assess H+ retention are invasive and have little clinical utility. We tested the hypothesis that urine excretion of the pH-sensitive metabolite citrate can identify H+ retention in patients with reduced GFR but without overt metabolic acidosis. H+ retention was assessed based on the difference between observed and expected plasma total CO2 after an oral sodium bicarbonate load. The association between H+ retention and urine citrate excretion was evaluated in albuminuric CKD patients with eGFR 60-89 ml/min/1.73m2 (CKD 2, n=40) or >90 ml/min/1.73m2 (CKD 1, n = 26) before and after 30 days of base-producing fruits and vegetables. Baseline H+ retention was higher in CKD 2, while baseline urine citrate excretion was lower in CKD 2 compared to CKD 1. Base-producing fruits and vegetables decreased H+ retention in CKD 2 and increased urine citrate excretion in both groups. Thus, H+ retention is associated with lower urine citrate excretion, and reduction of H+ retention with a base-producing diet is associated with increased urine citrate excretion. These results support further exploration of the utility of urine citrate excretion to identify H+ retention in CKD patients with reduced eGFR but without metabolic acidosis, to determine their candidacy for kidney protection with dietary H+ reduction or alkali therapy.
Assuntos
Acidose/diagnóstico , Ácido Cítrico/urina , Rim/fisiopatologia , Eliminação Renal/fisiologia , Insuficiência Renal Crônica/complicações , Equilíbrio Ácido-Base/fisiologia , Acidose/etiologia , Acidose/urina , Adulto , Biomarcadores/urina , Ácido Cítrico/metabolismo , Progressão da Doença , Estudos de Viabilidade , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urinaRESUMO
Urinary chemistries vary widely in both health and disease and are affected by diet, volume status, medications, and disease states. When properly examined, these tests provide important insight into the mechanism and therapy of various clinical disorders that are first detected by abnormalities in plasma chemistries. These tests cannot be interpreted in isolation, but instead require knowledge of key clinical information, such as medications, physical examination, and plasma chemistries, to include kidney function. When used appropriately and with knowledge of limitations, urine chemistries can provide important insight into the pathophysiology and treatment of a wide variety of disorders.
Assuntos
Acidose/urina , Nefropatias/diagnóstico , Nefropatias/urina , Urinálise , Cloretos/urina , Humanos , Concentração Osmolar , Potássio/urina , Sódio/urinaRESUMO
Two consecutive experiments were carried out to determine efficacy of Megasphaera elsdenii inoculation in alleviation of subacute ruminal acidosis (SARA). In the first experiment, SARA was induced by feeding corn- and wheat-based diets (20%, 40%, 60% and 80% of TMR, DM basis) in six ruminally cannulated heifers. Continuous pH was obtained using data loggers embedded in rumen. In corn (80%)- and wheat (60%)-based diets ruminal pH ranged from 5.2 to 5.6 for 7.77 and 5.93 hr. In the second experiment (5 day), M. elsdenii (200 ml; 2.4 x 1010 cfu/ml) was inoculated during the first two days. During the SARA induction period, M. elsdenii and S. bovis in rumen liquor were more abundant in wheat-based feeding (7.97 and 8.77) than in corn-based feeding (7.06 and 7.95 per ml, log basis; p < 0.0001 for both). M. elsdenii inoculation increased total volatile fatty acids (VFA) concentration when corn-based diet was fed, whereas it decreased total VFA concentration when wheat-based diet was fed (p < 0.004). There was a decrease in the propionic acid proportion (24.04%-19.08%; p < 0.002), whereas no alteration in lactate and ammonia concentrations was observed. M. elsdenii inoculation increased protozoa count (from 5.39 to 5.55 per ml, log basis; p < 0.009) and decreased S. bovis count (from 9.18 to 7.95 per ml, log basis; p < 0.0001). The results suggest that M. elsdenii inoculation may help prevent SARA depending on dietary grain through altering rumen flora as reflected by a decrease in S. bovis count and an increase in protozoa count.
Assuntos
Acidose/veterinária , Doenças dos Bovinos/prevenção & controle , Megasphaera elsdenii , Rúmen/microbiologia , Gastropatias/veterinária , Acidose/sangue , Acidose/microbiologia , Acidose/urina , Animais , Glicemia , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/urina , Hematócrito , Concentração de Íons de Hidrogênio , Gastropatias/sangue , Gastropatias/microbiologia , Gastropatias/urinaRESUMO
In rats, we recently showed how a chronic metabolic acidosis simultaneously reduced urinary oxalate excretion and promoted oxalate secretion by the distal colon leading to the proposition that acid-base disturbances may trigger changes to renal and intestinal oxalate handling. The present study sought to reproduce and extend these observations using the mouse model, where the availability of targeted gene knockouts (KOs) would offer future opportunities to reveal some of the underlying transporters and mechanisms involved. Mice were provided with a sustained load of acid (NH4Cl), base (NaHCO3) or the carbonic anhydrase inhibitor acetazolamide (ATZ) for 7 days after which time the impacts on urinary oxalate excretion and its transport by the intestine were evaluated. Mice consuming NH4Cl developed a metabolic acidosis but urinary oxalate was only reduced 46% and not statistically different from the control group, while provision of NaHCO3 provoked a significant 2.6-fold increase in oxalate excretion. For mice receiving ATZ, the rate of urinary oxalate excretion did not change significantly. Critically, none of these treatments altered the fluxes of oxalate (or chloride) across the distal ileum, cecum or distal colon. Hence, we were unable to produce the same effects of a metabolic acidosis in mice that we had previously found in rats, failing to find any evidence of the 'gut-kidney axis' influencing oxalate handling in response to various acid-base challenges. Despite the potential advantages offered by KO mice, this model species is not suitable for exploring how acid-base status regulates oxalate handling between the kidney and intestine.
Assuntos
Acidose/metabolismo , Mucosa Intestinal/metabolismo , Cálculos Renais/metabolismo , Rim/metabolismo , Oxalatos/metabolismo , Acetazolamida/administração & dosagem , Acidose/induzido quimicamente , Acidose/urina , Cloreto de Amônio/toxicidade , Animais , Inibidores da Anidrase Carbônica/administração & dosagem , Anidrases Carbônicas/metabolismo , Modelos Animais de Doenças , Feminino , Homeostase/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Rim/efeitos dos fármacos , Cálculos Renais/urina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oxalatos/urina , Ratos , Eliminação Renal/efeitos dos fármacos , Especificidade da EspécieRESUMO
Pyroglutamic acid, an intermediate in glutathione metabolism, can lead to elevated anion gap metabolic acidosis as rare complication of acetaminophen therapy in adults. Acquired pyroglutamic acidosis has been observed primarily in settings associated with glutathione deficiency. Risk factors for glutathione deficiency include critical illness, chronic liver or kidney disease, advanced age, female gender, alcohol abuse, malnutrition, pregnancy, antiepileptic drugs, and chronic acetaminophen use. Diagnosis of pyroglutamic acidosis requires both the exclusion of common etiologies of increased anion gap metabolic acidosis and a high index of suspicion. Treatment involves discontinuation of acetaminophen, supportive care, and addressing risk factors for glutathione deficiency. The current report describes an ambulatory patient with multiple risk factors for glutathione deficiency, who developed recurrent pyroglutamic acidosis due to acetaminophen use with therapeutic blood levels of acetaminophen.
Assuntos
Acetaminofen/efeitos adversos , Acidose/induzido quimicamente , Ácido Pirrolidonocarboxílico/urina , Acetaminofen/uso terapêutico , Acidose/terapia , Acidose/urina , Adulto , Feminino , Humanos , Recidiva , Resultado do TratamentoRESUMO
The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease.
Assuntos
Acidose/complicações , Acidose/urina , Compostos de Amônio/urina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/urina , Desequilíbrio Ácido-Base/complicações , Desequilíbrio Ácido-Base/etiologia , Progressão da Doença , HumanosRESUMO
BACKGROUND: Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. MATERIALS AND METHODS: Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. RESULTS: Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. CONCLUSION: Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection.
Assuntos
Acidose , Compostos de Amônio/urina , Ponte Cardiopulmonar/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Cardiopatias , Complicações Pós-Operatórias/urina , Acidose/etiologia , Acidose/urina , Feminino , Cardiopatias/cirurgia , Cardiopatias/urina , Humanos , MasculinoRESUMO
Recently, we have established a model of severe stepwise normovolemic hemodilution to a hematocrit of 10 % in rats employing three different colloidal volume replacement solutions (Voluven, Volulyte and Gelafundin) that are routinely used in clinical practice at present. We did not see severe dilutional acidosis as to be expected, but a decline in urinary pH. We here looked on further mechanisms of renal acid excretion during normovolemic hemodilution. Bicarbonate, which had been removed during normovolemic hemodilution, was calculated with the help of the Henderson-Hasselbalch equation. The urinary amount of ammonium as well as phosphate was determined in residual probes. The absolute amount of free protons in urine was obtained from the pH of the respective samples. The amount of protons generated during normovolemic hemodilution was approximately 0.6 mmol. During experimental time (5.5 h), distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39 mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer constituted 0.04 mmol in every experimental group. Excretion of free protons was in the range of 10(-6) mmol. The present data prove that the prompt rise in urinary ammonium excretion is also valid for acute metabolic acidosis originating from severe normovolemic hemodilution.