sodium-bicarbonate and Anemia

The occurrence and pathogenesis of metabolic acidosis after renal transplantation is reviewed. Posttransplant acidosis is shown to be a key mechanism for major metabolic complications in mineral and muscle metabolism, and for anemia, discussed in the context of both acidosis and renal transplantation.. Continuous improvement in kidney transplant survival has shifted attention to long-term outcomes, specifically to disorders linked to cardiovascular disease, physical capacity and quality of life. Metabolic acidosis is gaining growing acceptance as a clinical entity and has occasionally come into focus in the context of renal transplantation. The possible link to metabolic disturbances resulting in impairment of musculoskeletal disorders and physical limitations, however, has not been considered specifically.. Available evidence suggests a high prevalence of (compensated) metabolic acidosis after renal transplantation, presenting as low serum bicarbonate and impaired renal acid excretion. This condition is associated with relevant disorders in mineral metabolism and muscle function. Current knowledge about the effects of acidosis on renal electrolyte handling, mineral metabolism and protein synthesis suggests that acid/base derangements contribute to the muscle and bone pathology, as well as anemia, encountered after kidney transplantation. Consequently, posttransplant acidosis may be a relevant factor in the causal pathway of impaired physical capacity observed in this patient group.

Topics: Acidosis; Acidosis, Renal Tubular; Anemia; Bone Diseases, Endocrine; Humans; Insulin Resistance; Kidney Transplantation; Muscular Diseases; Nephrons; Prognosis; Quality of Life; Sodium Bicarbonate

A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 μmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.. 患者女性，47岁。因恶心、呕吐半年，发现肾功能异常（血肌酐255 μmol/L）3 d就诊，入院检查发现近端肾小管酸中毒合并贫血，排除自身免疫病、药物、毒物、单克隆免疫球蛋白病等继发因素，肾脏穿刺活检组织病理提示急性间质性肾炎，予泼尼松50 mg/d；碳酸氢钠4 g，3次/d；促红细胞生成素3 000 U，2次/周；氯化钾缓释片500 mg，3次/d；碳酸钙500 mg，3次/d；骨化三醇0.5 μg，1次/d。患者血肌酐恢复至90 μmol/L，但随诊期间患者恶心呕吐加重，再次检查发现合并乳酸酸中毒（乳酸14.1 mmol/L）。骨髓穿刺提示非霍奇金淋巴瘤，予CHOP方案化疗，期间乳酸酸中毒逐步好转（乳酸由14.5 mmol/L降至3.1 mmol/L），半个月后发生重症耶氏肺孢子菌肺炎，最终放弃治疗出院。.

Topics: Acidosis, Lactic; Acidosis, Renal Tubular; Anemia; Antineoplastic Agents; Biopsy; Creatinine; Erythropoietin; Female; Humans; Lymphoma, Non-Hodgkin; Middle Aged; Nausea; Pneumonia, Pneumocystis; Prednisone; Renal Insufficiency; Sodium Bicarbonate; Treatment Refusal; Vomiting

We have identified a novel homozygous nonsense mutation (W516X) in the kidney-type electrogenic sodium bicarbonate cotransporter 1 (NBC1) in a patient with isolated proximal renal tubular acidosis (pRTA). To specifically address the pathogenesis of this mutation, we created NBC1 W516X knock-in mice to match the patient's abnormalities. The expression of NBC1 mRNA and protein in the kidneys of NBC1(W516X/W516X) mice were virtually absent, indicating that nonsense-mediated mRNA decay (NMD) is involved in the defective transcription and translation of this mutation. These mice not only recapitulated the phenotypes of this patient with growth retardation, pRTA, and ocular abnormalities, but also showed anemia, volume depletion, prerenal azotemia, and several organ abnormalities, culminating in dehydration and renal failure with early lethality before weaning. In isolated renal proximal tubules, both NBC1 activity and the rate of bicarbonate absorption were markedly reduced. Unexpectedly, there was no compensatory increase in mRNA of distal acid/base transporters. Sodium bicarbonate but not saline administration to these mutant mice markedly prolonged their survival, decreased their protein catabolism and attenuated organ abnormalities. The prolonged survival time uncovered the development of corneal opacities due to corneal edema. Thus, NBC1(W516X/W516X) mice with pRTA represent an animal model for metabolic acidosis and may be useful for testing therapeutic inhibition of NMD in vivo.

Topics: Acidosis; Acidosis, Renal Tubular; Age Factors; Aging; Analysis of Variance; Anemia; Animals; Aquaporin 2; Bicarbonates; Codon, Nonsense; Corneal Opacity; Disease Models, Animal; Female; Gene Knock-In Techniques; Genotype; Growth Disorders; Homozygote; Humans; Hydrogen-Ion Concentration; Kidney Tubules, Proximal; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Phenotype; RNA, Messenger; Severity of Illness Index; Sodium Bicarbonate; Sodium-Bicarbonate Symporters; Transcription, Genetic

This study was designed to determine if coexisting metabolic acidosis or normovolaemic haemodilution, or both, modifies the acute cardiodepressant effect of i.v. sodium bicarbonate. Thirty-one mongrel dogs were anaesthetized with halothane, and the lungs ventilated mechanically; dogs were allocated randomly to one of four groups: control group (pHa 7.39 (SD 0.03), base excess -1.0 (1.6) mmol litre-1, haemoglobin 13.9 (2.5) g dl-1 (n = 8)), metabolic acidosis group (pHa 7.21 (0.05), base excess -11.2 (2.1) mmol litre1, haemoglobin 13.4 (2.6) g dl-1 (n = 8)), anaemia group (pHa 7.40 (0.04), base excess 0.1 (2.0) mmol litre-1, haemoglobin 7.2 (1.1) g dl-1 (n = 8)) or anaemia acidosis group (pHa 7.22 (0.04), base excess -11.0 (2.2) mmol litre-1, haemoglobin 7.4 (0.3) g dl-1 (n = 7)). Metabolic acidosis was induced by continuous i.v. infusion of hydrochloric acid 2 mol litre-1. Normovolaemic haemodilution was undertaken by phlebotomy and simultaneous exchange with lactated Ringer's solution at 37 degrees C. Mean arterial pressure (MAP), pulmonary artery pressure, right atrial pressure (RAP), maximum rate of change of pressure in the right ventricle (RV dP/dtmax) and pulmonary blood flow (PBF) were measured at 30 s, 1 and 3 min after administration of 7% sodium bicarbonate solution 1 mmol kg-1 given into the right atrium over 5 s. Sodium bicarbonate produced significant decreases in MAP and RV dP/dtmax at 30 s in all groups except for the anaemia acidosis group (P < 0.05). There was a significant decrease in right ventricular stroke volume in the metabolic acidosis group from baseline values (P < 0.05), and compared with the three other groups (P < 0.05). These results indicate that the cardiodepressant effect of sodium bicarbonate 1 mmol kg-1 i.v. during metabolic acidosis was more pronounced than without acidosis, but was attenuated in the presence of normovolaemic haemodilution.

Topics: Acidosis; Acidosis, Respiratory; Anemia; Animals; Depression, Chemical; Dogs; Female; Hemodilution; Hemodynamics; Hydrogen-Ion Concentration; Male; Sodium Bicarbonate