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1.
Am J Physiol Renal Physiol ; 318(2): F363-F374, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31790303

RESUMO

In stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of stones. Calcium phosphate (CaP) SFs have higher urine pH than calcium oxalate (CaOx) SFs. Normal women have higher urine pH than men on fixed diets, accompanied by greater absorption of food alkali. Female CaP and male CaOx SFs have similar urine pH as same sex normal individuals, but male CaP and female CaOx SFs may have abnormal acid-base handling. We studied 25 normal individuals (13 men and 12 women), 17 CaOx SFs (11 men and 6 women), and 15 CaP SFs (8 men and 7 women) on fixed diets. Urine and blood samples were collected under fasting and fed conditions. Female CaOx SFs had lower urine pH and lower alkali absorption, fed, compared with normal women; their urine NH4 was higher and urine citrate excretion lower than in normal women, consistent with their higher net acid excretion. Male CaOx SFs had higher urine citrate excretion and higher serum ultrafilterable citrate levels than normal men. Both male and female CaP SFs had higher urine pH fasting than same sex normal individuals, but only men were higher in the fed period, and there were no differences from normal in gut alkali absorption. CaP SFs of both sexes had higher urine NH4 and lower urine citrate than same sex normal individuals. The lower urine pH of female CaOx SFs seems related to decreased gut alkali absorption, while the higher pH of CaP SFs, accompanied by higher urine NH4 and lower urine citrate, suggests a proximal tubule disorder.


Assuntos
Equilíbrio Ácido-Base , Desequilíbrio Ácido-Base/urina , Oxalato de Cálcio/urina , Fosfatos de Cálcio/urina , Hipercalciúria/urina , Cálculos Renais/urina , Túbulos Renais Proximais/metabolismo , Desequilíbrio Ácido-Base/sangue , Desequilíbrio Ácido-Base/diagnóstico , Desequilíbrio Ácido-Base/fisiopatologia , Adulto , Compostos de Amônio/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Ácido Cítrico/urina , Cristalização , Dieta/efeitos adversos , Feminino , Absorção Gastrointestinal , Humanos , Concentração de Íons de Hidrogênio , Hipercalciúria/sangue , Hipercalciúria/diagnóstico , Hipercalciúria/fisiopatologia , Cálculos Renais/sangue , Cálculos Renais/diagnóstico , Cálculos Renais/fisiopatologia , Túbulos Renais Proximais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Adulto Jovem
2.
J Anim Physiol Anim Nutr (Berl) ; 103(5): 1571-1577, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31241230

RESUMO

Previous studies have shown that the intravenous infusion of inorganic phosphate increased urinary ammonium excretion 8- to 10-fold in the acidotic rabbit. This was considered to be a very important observation at the time and to be unique to the rabbit. While investigating this finding, we discovered that the formol titration procedure, used to measure urinary ammonium by this research group, is subject to interference by phosphate, casting doubt on the validity of the urinary ammonium excretion data reported by them in the literature. In order to re-assess the importance of phosphate as a potential modulator of urinary ammonium excretion in the acidotic rabbit, renal net acid excretion studies were carried out in phosphate-loaded acidotic animals. We observed that while urinary ammonium excretion increased significantly (p < 0.05) after 50 min of phosphate infusion, the maximum concentrations excreted were substantially less than previously reported in the literature. However, through its urinary buffering capacity, we observed that inorganic phosphate, via an experimentally induced phosphaturia, could substantially enhance titratable acid excretion. Contrary to earlier reports, we demonstrated that phosphate plays a relatively minor in vivo modulator role in enhancing renal net acid excretion through the vehicle of ammonium during acute metabolic acidosis in the hyperphosphataemic rabbit. The findings reported in this study constitute an important update on ammonia metabolism in the acidotic rabbit.


Assuntos
Acidose/veterinária , Compostos de Amônio/urina , Fosfatos/metabolismo , Equilíbrio Ácido-Base , Acidose/induzido quimicamente , Animais , Concentração de Íons de Hidrogênio , Masculino , Coelhos , Organismos Livres de Patógenos Específicos , Urinálise
3.
Am J Kidney Dis ; 74(2): 203-212, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30910373

RESUMO

RATIONALE & OBJECTIVE: Higher urine net acid excretion (NAE) is associated with slower chronic kidney disease progression, particularly in patients with diabetes mellitus. To better understand potential mechanisms and assess modifiable components, we explored independent predictors of NAE in the CRIC (Chronic Renal Insufficiency Cohort) Study. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: A randomly selected subcohort of adults with chronic kidney disease enrolled in the CRIC Study with NAE measurements. PREDICTORS: A comprehensive set of variables across prespecified domains including demographics, comorbid conditions, medications, laboratory values, diet, physical activity, and body composition. OUTCOME: 24-hour urine NAE. ANALYTICAL APPROACH: NAE was defined as the sum of urine ammonium and calculated titratable acidity in a subset of CRIC participants. 22 individuals were excluded for urine pH < 4 (n = 1) or ≥7.4 (n = 19) or extreme outliers of NAE values (n = 2). From an analytic sample of 978, we identified the association of individual variables with NAE in the selected domains using linear regression. We estimated the percent variance explained by each domain using the adjusted R2 from a domain-specific model. RESULTS: Mean NAE was 33.2 ± 17.4 (SD) mEq/d. Multiple variables were associated with NAE in models adjusted for age, sex, estimated glomerular filtration rate (eGFR), race/ethnicity, and body surface area, including insulin resistance, dietary potential renal acid load, and a variety of metabolically active medications (eg, metformin, allopurinol, and nonstatin lipid agents). Body size, as indicated by body surface area, body mass index, or fat-free mass; race/ethnicity; and eGFR also were independently associated with NAE. By domains, more variance was explained by demographics, body composition, and laboratory values, which included eGFR and serum bicarbonate level. LIMITATIONS: Cross-sectional; use of stored biological samples. CONCLUSIONS: NAE relates to several clinical domains including body composition, kidney function, and diet, but also to metabolic factors such as insulin resistance and the use of metabolically active medications.


Assuntos
Compostos de Amônio/urina , Insuficiência Renal Crônica/urina , Idoso , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/metabolismo
4.
Kidney Int ; 95(5): 1262-1268, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30795852

RESUMO

Idiopathic uric acid nephrolithiasis is characterized by an overly acidic urine pH caused by the combination of increased acid production and inadequate buffering of urinary protons by ammonia. A large proportion of uric acid stone formers exhibit features of the metabolic syndrome. We previously demonstrated that thiazolidinediones improved the urinary biochemical profile in an animal model of the metabolic syndrome. In this proof-of-concept study, we examined whether the thiazolidinedione pioglitazone can also ameliorate the overly acidic urine in uric acid stone formers. Thirty-six adults with idiopathic uric acid nephrolithiasis were randomized to pioglitazone 30 mg/day or matching placebo for 24 weeks. At baseline and study end, participants underwent collection of blood and 24-hour urine in an inpatient research unit while consuming a fixed metabolic diet, followed by assessment of the ammoniagenic response to an acute oral acid load. Twenty-eight participants completed the study. Pioglitazone treatment improved features of the metabolic syndrome. Pioglitazone also reduced net acid excretion and increased urine pH (5.37 to 5.59), the proportion of net acid excreted as ammonium, and ammonium excretion in response to an acute acid load, whereas these parameters were unchanged with placebo. Treatment of patients with idiopathic uric acid nephrolithiasis with pioglitazone for 24 weeks led to a reduction in the acid load presented to the kidney and a more robust ammoniagenesis and ammonium excretion, resulting in significantly higher urine pH. Future studies should consider the impact of this targeted therapy on uric acid stone formation.


Assuntos
Cálculos Renais/tratamento farmacológico , Pioglitazona/administração & dosagem , Eliminação Renal/efeitos dos fármacos , Ácido Úrico/urina , Adulto , Idoso , Compostos de Amônio/metabolismo , Compostos de Amônio/urina , Feminino , Humanos , Concentração de Íons de Hidrogênio , Cálculos Renais/urina , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Ácido Úrico/metabolismo
7.
Adv Chronic Kidney Dis ; 25(4): 334-350, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30139460

RESUMO

Renal tubular acidosis (RTA) represents a group of diseases characterized by (1) a normal anion gap metabolic acidosis; (2) abnormalities in renal HCO3- absorption or new renal HCO3- generation; (3) changes in renal NH4+, Ca2+, K+, and H2O homeostasis; and (4) extrarenal manifestations that provide etiologic diagnostic clues. The focus of this review is to give a general overview of the pathogenesis of the various clinical syndromes causing RTA with a particular emphasis on type I (hypokalemic distal RTA) and type II (proximal) RTA while reviewing their pathogenesis from a physiological "bottom-up" approach. In addition, the factors involved in the generation of metabolic acidosis in both type I and II RTA are reviewed highlighting the importance of altered renal ammonia production/partitioning and new HCO3- generation. Our understanding of the underlying tubular transport and extrarenal abnormalities has significantly improved since the first recognition of RTA as a clinical entity because of significant advances in clinical acid-base chemistry, whole tubule and single-cell H+/base transport, and the molecular characterization of the various transporters and channels that are functionally affected in patients with RTA. Despite these advances, additional studies are needed to address the underlying mechanisms involved in hypokalemia, altered ammonia production/partitioning, hypercalciuria, nephrocalcinosis, cystic abnormalities, and CKD progression in these patients.


Assuntos
Desequilíbrio Ácido-Base , Acidose Tubular Renal/fisiopatologia , Amônia/metabolismo , Bicarbonatos/metabolismo , Túbulos Renais Proximais/fisiopatologia , Acidose Tubular Renal/complicações , Compostos de Amônio/urina , Animais , Transporte Biológico , Cálcio/metabolismo , Ácido Cítrico/urina , Humanos , Hipercalciúria/etiologia , Hipopotassemia/etiologia , Ácidos Cetoglutáricos/metabolismo , Túbulos Renais Distais/fisiopatologia , Simportadores de Sódio-Bicarbonato/genética
8.
Am J Physiol Renal Physiol ; 315(2): F231-F237, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29631356

RESUMO

Dietary and urinary risk factors have been implicated in conditions favoring ammonium urate nephrolithiasis in managed dolphins compared with free-ranging dolphins. In this study, urine samples were collected from 16 dolphins (8 cases, 8 controls) from the U.S. Navy Marine Mammal Program for the purposes of assessing changes in urinary biomarkers after a large meal. Urinary biomarkers and nephrolithiasis presence were assessed opportunistically in 15 long-term resident free-ranging dolphins living in Sarasota Bay, Florida. Additionally, the total purine contents of fish commonly consumed by each dolphin population were measured to evaluate potential dietary risk factors. Populations were compared for total dietary purine composition, recently fed status, nephrolithiasis presence, and differences in urinary biochemical, acid-base, and physicochemical parameters via Wilcoxon rank sum analysis and least square means. Managed dolphins had higher urinary pH and ammonium ([Formula: see text]) in both pre- and postprandial conditions and higher urinary uric acid and saturation indices of NH4U in the postprandial condition compared with free-ranging dolphins ( P < 0.05). The purine content was greater ( P < 0.0001) in the diet consumed by managed dolphins [7 mmol/Mcal metabolizable energy (ME)] than in the free-ranging dolphin diet (4 mmol/Mcal ME). Free-ranging dolphins did not show evidence of nephrolithiasis. Observed differences in urinary biomarkers and dietary purine content in these two dolphin populations suggest a pathophysiologic basis for the role of fish types on the risk of NH4U stone formation. Future research should investigate fish type and feeding frequency, inhibitors and promoters, and alkalinizing therapy for reducing NH4U nephrolithiasis in dolphins.


Assuntos
Compostos de Amônio/urina , Golfinho Nariz-de-Garrafa/urina , Dieta/veterinária , Peixes/metabolismo , Nefrolitíase/veterinária , Purinas/metabolismo , Ácido Úrico/urina , Animais , Animais Selvagens , Dieta/efeitos adversos , Feminino , Masculino , Nefrolitíase/diagnóstico por imagem , Nefrolitíase/etiologia , Nefrolitíase/urina , Período Pós-Prandial , Purinas/efeitos adversos , Fatores de Risco , Ultrassonografia
9.
Am J Physiol Renal Physiol ; 315(2): F313-F322, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29667915

RESUMO

Prolonged lithium treatment is associated with various renal side effects and is known to induce inner medullary collecting duct (IMCD) remodeling. In animals treated with lithium, the fraction of intercalated cells (ICs), which are responsible for acid-base homeostasis, increases compared with renal principal cells (PCs). To investigate the intricacies of lithium-induced IMCD remodeling, male Sprague-Dawley rats were fed a lithium-enriched diet for 0,1, 2, 3, 6, 9, or 12 wk. Urine osmolality was decreased at 1 wk, and from 2 to 12 wk, animals were severely polyuric. After 6 wk of lithium treatment, approximately one-quarter of the cells in the initial IMCD expressed vacuolar H+-ATPase, an IC marker. These cells were localized in portions of the inner medulla, where ICs are not normally found. Pendrin, a Cl-/[Formula: see text] exchanger, is normally expressed only in two IC subtypes found in the convoluted tubule, the cortical collecting duct, and the connecting tubule. At 6 wk of lithium treatment, we observed various patterns of pendrin localization and expression in the rat IMCD, including a novel phenotype wherein pendrin was coexpressed with aquaporin-4. These observations collectively suggest that renal IMCD cell plasticity may play an important role in lithium-induced IMCD remodeling.


Assuntos
Plasticidade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antiportadores de Cloreto-Bicarbonato/metabolismo , Túbulos Renais Coletores/efeitos dos fármacos , Carbonato de Lítio/toxicidade , Transportadores de Sulfato/metabolismo , Compostos de Amônio/urina , Animais , Aquaporina 4/metabolismo , Antiportadores de Cloreto-Bicarbonato/genética , Esquema de Medicação , Regulação da Expressão Gênica , Concentração de Íons de Hidrogênio , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Masculino , Concentração Osmolar , Fenótipo , Poliúria/induzido quimicamente , Poliúria/patologia , Poliúria/urina , Ratos Sprague-Dawley , Transdução de Sinais , Transportadores de Sulfato/genética , Fatores de Tempo , ATPases Vacuolares Próton-Translocadoras/metabolismo
11.
Nephron ; 138(3): 222-228, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29050011

RESUMO

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 , Humanos
12.
Clin J Am Soc Nephrol ; 13(2): 223-230, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29146699

RESUMO

BACKGROUND AND OBJECTIVES: Urinary ammonium excretion increases in response to nonvolatile acids to maintain normal systemic bicarbonate and pH. However, enhanced ammonia production promotes tubulointerstitial fibrosis in animal models. Therefore, a subset of individuals with CKD and normal bicarbonate may have acid-mediated kidney fibrosis that might be better linked with ammonium excretion than bicarbonate. We hypothesized that urine TGF-ß1, as an indicator of kidney fibrosis, would be more tightly linked with urine ammonium excretion than serum bicarbonate and other acid-base indicators. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum bicarbonate and urinary ammonium, titratable acids, pH, and TGF-ß1/creatinine in 144 persons with CKD. Multivariable-adjusted linear regression models determined the cross-sectional association between TGF-ß1/creatinine and serum bicarbonate, urine ammonium excretion, urine titratable acids excretion, and urine pH. RESULTS: Mean eGFR was 42 ml/min per 1.73 m2, mean age was 65 years old, 78% were men, and 62% had diabetes. Mean urinary TGF-ß1/creatinine was 102 (49) ng/g, mean ammonium excretion was 1.27 (0.72) mEq/h, mean titratable acids excretion was 1.14 (0.65) mEq/h, mean urine pH was 5.6 (0.5), and mean serum bicarbonate was 23 (3) mEq/L. After adjusting for eGFR, proteinuria, and other potential confounders, each SD increase of urine ammonium and urine pH was associated with a statistically significant 1.22-fold (95% confidence interval, 1.11 to 1.35) or 1.11-fold (95% confidence interval, 1.02 to 1.21) higher geometric mean urine TGF-ß1/creatinine, respectively. Each SD increase of serum bicarbonate and urine titratable acids was associated with a nonsignificant 1.06-fold (95% confidence interval, 0.97 to 1.16) or 1.03-fold (95% confidence interval, 0.92 to 1.14) higher geometric mean urine TGF-ß1/creatinine, respectively. CONCLUSIONS: Urinary ammonium excretion but not serum bicarbonate is associated with higher urine TGF-ß1/creatinine.


Assuntos
Compostos de Amônio/urina , Insuficiência Renal Crônica/urina , Fator de Crescimento Transformador beta1/urina , Idoso , Idoso de 80 Anos ou mais , Bicarbonatos/sangue , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/urina , Estudos Transversais , Feminino , Fibrose , Taxa de Filtração Glomerular , Humanos , Concentração de Íons de Hidrogênio , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Eliminação Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia
13.
Clin J Am Soc Nephrol ; 13(2): 205-212, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29097482

RESUMO

BACKGROUND AND OBJECTIVES: Low urine ammonium excretion is associated with ESRD in CKD. Few laboratories measure urine ammonium, limiting clinical application. We determined correlations between urine ammonium, the standard urine anion gap, and a modified urine anion gap that includes sulfate and phosphate and compared risks of ESRD or death between these ammonium estimates and directly measured ammonium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured ammonium, sodium, potassium, chloride, phosphate, and sulfate from baseline 24-hour urine collections in 1044 African-American Study of Kidney Disease and Hypertension participants. We evaluated the cross-sectional correlations between urine ammonium, the standard urine anion gap (sodium + potassium - chloride), and a modified urine anion gap that includes urine phosphate and sulfate in the calculation. Multivariable-adjusted Cox models determined the associations of the standard urine anion gap and the modified urine anion gap with the composite end point of death or ESRD; these results were compared with results using urine ammonium as the predictor of interest. RESULTS: The standard urine anion gap had a weak and direct correlation with urine ammonium (r=0.18), whereas the modified urine anion gap had a modest inverse relationship with urine ammonium (r=-0.58). Compared with the highest tertile of urine ammonium, those in the lowest urine ammonium tertile had higher risk of ESRD or death (hazard ratio, 1.46; 95% confidence interval, 1.13 to 1.87) after adjusting for demographics, GFR, proteinuria, and other confounders. In comparison, participants in the corresponding standard urine anion gap tertile did not have higher risk of ESRD or death (hazard ratio, 0.82; 95% confidence interval, 0.64 to 1.07), whereas the risk for those in the corresponding modified urine anion gap tertile (hazard ratio, 1.32; 95% confidence interval, 1.03 to 1.68) approximated that of directly measured urine ammonium. CONCLUSIONS: Urine anion gap is a poor surrogate of urine ammonium in CKD unless phosphate and sulfate are included in the calculation. Because the modified urine anion gap merely estimates urine ammonium and requires five measurements, direct measurements of urine ammonium are preferable in CKD.


Assuntos
Equilíbrio Ácido-Base , Compostos de Amônio/urina , Falência Renal Crônica/urina , Insuficiência Renal Crônica/urina , Adolescente , Adulto , Afro-Americanos , Idoso , Biomarcadores/urina , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/etnologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fosfatos/urina , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/etnologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Sulfatos/urina , Estados Unidos/epidemiologia , Urinálise , Adulto Jovem
14.
J Nephrol ; 31(3): 385-393, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29178032

RESUMO

Previous reports identify a voltage dependent distal renal tubular acidosis (dRTA) secondary to lithium (Li+) salt administration. This was based on the inability of Li+-treated patients to increase the urine-blood (U-B) pCO2 when challenged with NaHCO3 and, the ability of sodium neutral phosphate or Na2SO4 administration to restore U-B pCO2 in experimental animal models. The underlying mechanisms for the Li+-induced dRTA are still unknown. To address this point, a 7 days time course of the urinary acid-base parameters was investigated in rats challenged with LiCl, LiCitrate, NaCl, or NaCitrate. LiCl induced the largest polyuria and a mild metabolic acidosis. Li+-treatment induced a biphasic response. In the first 2 days, proper urine volume and acidification occurred, while from the 3rd day of treatment, polyuria developed progressively. In this latter phase, the LiCl-treated group progressively excreted more NH4+ and less pCO2, suggesting that NH3/NH4+ became the main urinary buffer. This physiological parameter was corroborated by the upregulation of NBCn1 (a marker of increased ammonium recycling) in the inner stripe of outer medulla of LiCl treated rats. Finally, by investigating NH4+ excretion in ENaC-cKO mice, a model resistant to Li+-induced polyuria, a primary role of the CD was confirmed. By definition, dRTA is characterized by deficient urinary ammonium excretion. Our data question the presence of a voltage-dependent Li+-induced dRTA in rats treated with LiCl for 7 days and the data suggest that the alkaline urine pH induced by NH3/NH4+ as the main buffer has lead to the interpretation dRTA in previous studies.


Assuntos
Acidose Tubular Renal/induzido quimicamente , Acidose Tubular Renal/urina , Compostos de Amônio/urina , Dióxido de Carbono/urina , Túbulos Renais Distais , Poliúria/urina , Animais , Tampões (Química) , Dióxido de Carbono/sangue , Citratos/efeitos adversos , Canais Epiteliais de Sódio/genética , Concentração de Íons de Hidrogênio , Medula Renal/metabolismo , Túbulos Renais Coletores/fisiopatologia , Cloreto de Lítio/efeitos adversos , Masculino , Camundongos , Camundongos Knockout , Pressão Parcial , Poliúria/induzido quimicamente , Poliúria/genética , Ratos , Cloreto de Sódio/efeitos adversos , Citrato de Sódio/efeitos adversos , Simportadores de Sódio-Bicarbonato/metabolismo , Fatores de Tempo , Urinálise
15.
Biomed Res Int ; 2017: 5383574, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28612026

RESUMO

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 , Masculino
16.
Physiol Res ; 66(4): 615-620, 2017 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-28406701

RESUMO

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.


Assuntos
Acidose/urina , Compostos de Amônio/urina , Hemodiluição/efeitos adversos , Modelos Animais , Índice de Gravidade de Doença , Acidose/fisiopatologia , Animais , Hemodiluição/métodos , Masculino , Ratos , Ratos Wistar
17.
J Anim Sci ; 95(3): 1396-1406, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28380506

RESUMO

Ammonium urate nephrolithiasis frequently develops in common bottlenose dolphins () managed under human care but is rare in free-ranging common bottlenose dolphins. In other species, the dietary cation-anion difference (DCAD) can affect ammonium urate urolith formation by increasing proton excretion as ammonium ions. Therefore, differences in diet between the 2 dolphin populations could affect urolith formation, but the DCAD of most species consumed by free-ranging and managed dolphins is unknown. To compare the nutrient composition of diets consumed by free-ranging and managed bottlenose dolphins, samples ( = 5) of the 8 species of fish commonly consumed by free-ranging bottlenose dolphins in Sarasota Bay, FL, and the 7 species of fish and squid commonly fed to managed bottlenose dolphins were analyzed for nutrient content. Metabolizable energy was calculated using Atwater factors; the DCAD was calculated using 4 equations commonly used in people and animals that use different absorption coefficients. The nutrient composition of individual species was used to predict the DCAD of 2 model diets typically fed to managed common bottlenose dolphins and a model diet typically consumed by common bottlenose dolphins in Sarasota Bay. To mimic differences in postmortem handling of fish for the 2 populations of bottlenose dolphins, "free-ranging" samples were immediately frozen at -80°C and minimally thawed before analysis, whereas "managed" samples were frozen for 6 to 9 mo at -18°C and completely thawed. "Free-ranging" species contained more Ca and P and less Na and Cl than "managed" fish and squid species. As a consequence, the DCAD of both model managed dolphin diets obtained using 3 of the 4 equations was much more negative than the DCAD of the model free-ranging bottlenose dolphin diet ( < 0.05). The results imply that managed bottlenose dolphins must excrete more protons in urine than free-ranging bottlenose dolphins, which will promote nephrolith formation. The nutrient composition of the free-ranging bottlenose dolphin diet, determined for the first time here, can be used as a guide for feeding managed bottlenose dolphins, but research in vivo is warranted to determine whether adding more cations to the diet will prevent urolith formation in managed dolphins.


Assuntos
Compostos de Amônio/urina , Ânions/metabolismo , Golfinho Nariz-de-Garrafa/fisiologia , Cátions/metabolismo , Nefrolitíase/veterinária , Ácido Úrico/urina , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Animais Selvagens , Animais de Zoológico , Dieta/veterinária , Metabolismo Energético , Feminino , Peixes , Humanos , Masculino , Nefrolitíase/urina
18.
J Am Soc Nephrol ; 28(8): 2483-2490, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28385806

RESUMO

Metabolic acidosis is associated with poor outcomes in CKD. Because impaired renal ammonium excretion is important in the pathogenesis of acidosis, urine ammonium excretion might be a better and perhaps earlier acid-base indicator of risk than serum bicarbonate, particularly in patients without acidosis. We evaluated the association between baseline ammonium excretion and clinical outcomes in African American Study of Kidney Disease and Hypertension participants (n=1044). Median daily ammonium excretion was 19.5 (95% confidence interval [95% CI], 6.5 to 43.2) mEq. In Cox regression models (adjusted for demographics, measured GFR, proteinuria, body mass index, net endogenous acid production, and serum potassium and bicarbonate), hazard ratios of the composite outcome of death or dialysis were 1.46 (95% CI, 1.13 to 1.87) in the low tertile and 1.14 (95% CI, 0.89 to 1.46) in the middle tertile of daily ammonium excretion compared with the high tertile. Among participants without acidosis at baseline, the adjusted hazard ratio for those with ammonium excretion <20 mEq/d was 1.36 (95% CI, 1.09 to 1.71) compared with those with ammonium excretion ≥20 mEq/d. Additionally, compared with participants in the high ammonium tertile, those in the low ammonium tertile had higher adjusted odds of incident acidosis at 1 year (adjusted odds ratio, 2.56; 95% CI, 1.04 to 6.27). In conclusion, low ammonium excretion is associated with death and renal failure in hypertensive kidney disease, even among those without acidosis. Low ammonium excretion could identify patients with CKD and normal bicarbonate levels who might benefit from alkali before acidosis develops.


Assuntos
Compostos de Amônio/urina , Hipertensão Renal/urina , Nefrite/urina , Insuficiência Renal Crônica/urina , Acidose/complicações , Acidose/urina , Feminino , Humanos , Hipertensão Renal/complicações , Masculino , Pessoa de Meia-Idade , Nefrite/complicações , Prognóstico , Insuficiência Renal Crônica/complicações
19.
Curr Opin Pediatr ; 29(2): 206-210, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28092281

RESUMO

PURPOSE OF REVIEW: To facilitate the understanding and knowledge of renal tubular acidosis by providing a summarized information on the known clinical and biochemical characteristics of this group of diseases, by updating the genetic and molecular bases of the primary forms renal tubular acidosis and by examining some issues regarding the diagnosis of distal renal tubular acidosis (RTA) in the daily clinical practice. RECENT FINDINGS: The manuscript presents recent findings on the potential of next-generation sequencing to disclose new pathogenic variants in patients with a clinical diagnosis of primary RTA and negative Sanger sequencing of known genes. The current review emphasizes the importance of measuring urinary ammonium for a correct clinical approach to the patients with metabolic acidosis and discusses the diagnosis of incomplete distal RTA. SUMMARY: We briefly update the current information on RTA, put forward the need of additional studies in children to validate urinary indexes used in the diagnosis of RTA and offer a perspective on diagnostic genetic tests.


Assuntos
Acidose Tubular Renal/genética , Acidose Tubular Renal/fisiopatologia , Compostos de Amônio/urina , Rim/fisiopatologia , Acidose Tubular Renal/terapia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Prognóstico , Medição de Risco
20.
Kidney Int ; 91(1): 204-215, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27914710

RESUMO

Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24-hour urines from a random subset of 980 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. In multivariable models accounting for demographics, comorbidity and kidney function, higher NAE was significantly associated with lower serum bicarbonate (0.17 mEq/l lower serum bicarbonate per 10 mEq/day higher NAE), consistent with a larger acid load. Over a median of 6 years of follow-up, higher NAE was independently associated with a significantly lower risk of the composite of end-stage renal disease or halving of estimated glomerular filtration rate among diabetics (hazard ratio 0.88 per 10 mEq/day higher NAE), but not those without diabetes (hazard ratio 1.04 per 10 mEq/day higher NAE). For comparison, we estimated the nonvolatile acid load as net endogenous acid production using self-reported food frequency questionnaires from 2848 patients and dietary urine biomarkers from 3385 patients. Higher net endogenous acid production based on biomarkers (urea nitrogen and potassium) was modestly associated with faster CKD progression consistent with prior reports, but only among those without diabetes. Results from the food frequency questionnaires were not associated with CKD progression in any group. Thus, disparate results obtained from analyses of nonvolatile acid load directly measured as NAE and estimated from diet suggest a novel hypothesis that the risk of CKD progression related to low NAE or acid load may be due to diet-independent changes in acid production in diabetes.


Assuntos
Acidose/urina , Ácidos/metabolismo , Diabetes Mellitus/metabolismo , Eliminação Renal , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , Acidose/etiologia , Idoso , Compostos de Amônio/urina , Bicarbonatos/sangue , Biomarcadores/urina , Nitrogênio da Ureia Sanguínea , Diabetes Mellitus/urina , Progressão da Doença , Comportamento Alimentar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Fatores de Risco , Inquéritos e Questionários
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