Renal Excretion of Digoxin in Swine and Goats

In experiments on swine and goats the renal excretion of digoxin was examined, and it was found that the renal clearance of non-protein-bound digoxin in swine was lower than creatinine clearance which expresses filtration clearance. Correlation analysis showed that the renal clearance of digoxin in swine was not significantly influenced by the concentration of non-protein-bound digoxin in plasma and the pH of the urine, while there was a significant positive correlation between the clearance and the urine flow rate (Table 4). On the other hand, the renal clearance of digoxin in goats was significantly influenced by the concentration of non-proteinbound digoxin in plasma and by urine pH (Table 4). From these results it is concluded that glomerular filtration and back-diffusion are involved in the renal handling of digoxin in both swine and goats. In addition active tubular secretion is also involved in the renal excretion of digoxin in goats.     

Apparent reduction of endogenous creatinine clearance by salicylate treatment.

A prospective study of nine patients with rheumatoid arthritis and 11 healthy volunteers who started salicylate treatment showed that in 18 of the 20 subjects creatinine clearance values fell the average being 25%. Serum creatinine concentration was increased by an average of 38%, although blood urea levels were unchanged. Since 51Cr-edetic acid clearance tests performed at the same time in 12 of the subjects were not affected, the fall in creatinine clearance was probably not due to impaired glomerular function, and salicylate ingestion may therefore invalidate the creatinine clearance test as an index of glomerular filtration rate. It is clearly important to inquire into the patient''s analgesic comsumption when using the creatinine clearance test to assess glomerular function.     

Interactions of digoxin with nifedipine and diltiazem

Biological serum halt-life, relative volume of distribution and digoxin clearance following a single oral dose of digoxin with diltiazem or nifedipine were evaluated. Blood serum digoxin following its administration with diltiazem and nifedipine for 8 days were assayed. It was found that diltiazem and nifedipine did not affect tested pharmacokinetic parameters of digoxin and did not change digoxin serum levels during a 8-day administration in combination with diltiazem and nifedipine.     

Maintenance Digoxin in Elderly Patients

Digitalis glycosides remain the cornerstone of treatment in cardiac failure. The increasing frequency of toxic effects is a cause for concern. Review of 80 elderly patients receiving digoxin on a maintenance basis, some of whom had toxic effects, shows that in almost three-quarters of the group digoxin was stopped without detriment. Elderly patients on maintenance treatment should be reviewed, and in the absence of a known primary cardiac lesion an attempt should be made to withdraw digoxin.     

前列地尔联合尿毒清颗粒对慢性肾衰竭患者血清甲状旁腺激素、同型半胱氨酸水平及临床疗效的影响

目的:探究前列地尔联合尿毒清颗粒对慢性肾衰竭患者血清甲状旁腺激素、同型半胱氨酸及临床疗效的影响。方法:收集我院收治的慢性肾衰竭患者74例,根据随机对照表分为对照组和试验组,每组37例。对照组予以前列地尔注射液治疗,试验组在对照组基础上予以尿毒清颗粒治疗。观察并比较两组患者临床疗效,治疗前后血清肌酐(SCr)、尿素氮(BUN)、血尿酸(UA)、内生肌酐清除率(Ccr)、超敏C反应蛋白(hs-CRP)、同型半胱氨酸(Hcy)、甲状旁腺素(PTH)、β2微球蛋白(β2-MG)水平以及不良反应的发生情况。结果:与对照组相比,试验组治疗后临床总有效率较高(P0.05)。两组治疗后血清肌酐、尿素氮、血尿酸水平下降(P0.05),内生肌酐清除率水平升高(P0.05);与对照组相比,试验组血清肌酐、尿素氮、血尿酸水平较低(P0.05),内生肌酐清除率水平较高(P0.05)。两组治疗后超敏C反应蛋白、同型半胱氨酸、甲状旁腺素以及β2微球蛋白水平降低(P0.05);与对照组相比,试验组超敏C反应蛋白、同型半胱氨酸、甲状旁腺素以及β2微球蛋白水平较低(P0.05)。两组不良反应发生情况相比差异无统计学意义(P0.05)。结论:前列地尔联合尿毒清颗粒对慢性肾衰竭患者的临床疗效显著,安全性较高,可能与其下调血清甲状旁腺激素以、同型半胱氨酸及β2微球蛋白水平有关。     

Serum IgG and Renal Transplantation

In 57 patients with renal allografts the prolonged administration of prednisolone ≥ 1 mg/kg/day and azathioprine ≥ 3 mg/kg/day caused a significant and persistent fall in serum IgG at all levels of creatinine clearance. The fall in IgG was more striking when creatinine clearance was below 25 ml/min. At lower doses of azathioprine and prednisolone serum IgG fell when the creatinine clearance was less than 35 ml/min, the degree of recovery towards normal being dependent on creatinine clearance and dosage. Post-transplant haemodialysis decreased the depression of IgG, and patients with immediately functioning grafts had minimal IgG depression. An inverse relation between IgG and IgM was observed in some patients. Severe infections and toxicity were associated with the greatest reduction in IgG; leucopenia and thrombocytopenia were not consistently reliable guides to toxicity. The deaths of four patients (7%) were associated with severe infections. Falls in IgG were not related to the rejection process. IgG measurement should be used as a guide to immunosuppression and toxicity in renal allograft patients.     

Comparative Study of the Absorption,Plasma Levels,and Urinary Excretion of the “New” and the “Old” Lanoxin

A comparative study was performed of the absorption, the plasma level at equilibrium, and the urinary excretion of digoxin using two types of Lanoxin tablets, those produced before and after the 1972 alteration of the tablet manufacture.After a single dose the absorption rate of the new tablets was about twice as great as the old, both in young subjects and in the elderly patients. There were no significant differences in the plasma levels of digoxin for the two tablets 15 hours after the last administration in patients on an equal maintenance dose. The urinary excretion of digoxin increased about 40% when the “old” Lanoxin was replaced by the “new.” In elderly patients a daily dose of 0·125 mg twice daily of the new tablets should be sufficient to reach the therapeutic range. Young people need a higher dosage. If the kidney function is reduced by as much as 50% the dose should be reduced.     

Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig.

The synthesis of 17 alpha-acetoxy-3 beta-[(beta-D-glucopyranosyl)oxy]- 6 alpha-methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20 beta-hydroxy-3 beta-[(alpha-L-rhamnopyranosyl)oxy]-5 beta, 14 beta-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14 beta-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit [3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes.     

Bone fracture in elderly female with primary hyperparathyroidism: relationship among renal function, vitamin D status and fracture risk

Among 12 aged postmenopausal females with primary hyperparathyroidism, 5 had no bone fracture and 7 had fractures. Both serum 1,25 (OH)2D levels and creatinine clearance values in patients with fracture were significantly lower than those without fracture (p less than 0.025). In addition, significant positive correlation was observed between serum 1,25 (OH)2D levels and creatinine clearance values (p less than 0.05). These data suggest that decreased serum 1,25 (OH)2D level due to renal dysfunction may causally correlate to bone fracture in postmenopausal primary hyperparathyroidism.     

Ceftazidime does not enhance cyclosporin-A nephrotoxicity in febrile bone marrow transplantation patients

Ceftazidime was used as monotherapy for 30 febrile episodes in 28 patients, who underwent allogeneic bone marrow transplantation and who were treated concomitantly with the immunosuppressive agent cyclosporin-A. Ceftazidime did not enhance the well established nephrotoxicity of cyclosporin-A as measured by serum creatinine levels or creatinine clearance. Although an increasing number of Gram-positive infections in these patients warrants vigilance, ceftazidime as initial empirical monotherapy proved to be successful in 95% of all febrile post-transplantation patients. All Gram-negative and 69% of the Gram-positive infections were cured with ceftazidime alone. The overall clinical cure rate was 72%, with microbiological clearance in 63%. This compares favourably with aminoglycoside containing schedules and avoids the aminoglycoside associated nephrotoxicity.     

Serum, urinary, and salivary nitric oxide in rheumatoid arthritis: complexities of interpreting nitric oxide measures

Nitric oxide (NO) may play important roles in rheumatoid arthritis (RA). RA is an inflammatory disease involving joints and other systems including salivary glands. To assess NO production in RA patients, we compared levels of serum, urine, and salivary nitrite and nitrate (NOx) in patients with RA and normal subjects, and we examined the relationships of these measures to disease activity. Serum, urine, and NOx levels as well as renal creatinine, NOx clearance and fractional excretion rates were compared in 25 RA patients and 20 age- and gender-matched healthy controls. Subjects were hospitalized for 3 days and placed on a NOxrestricted diet. NOx was assayed using nitrate reductase and the Griess reagent. RA activity was assessed using standard clinical and laboratory measures. While consuming a restricted diet for 3 days to eliminate the effects of oral intake of NOx, 24 hour urinary NOx excretion decreased in both RA patients and healthy controls. Urine NOx levels at all time points were not significantly different between RA patients and normal subjects. Serum NOx levels also decreased during the 3 days of NOx restriction, but RA patients had higher serum NOx levels at all time points compared with the control group. Likewise, serum NOx/creatinine ratios were higher in RA patients than in controls. Although basal salivary flow rate and tear flow were lower in RA patients, salivary NOx levels did not differ between normal and RA subjects. While renal creatinine clearance was not different between the two groups, we found that RA patients had lower renal NOx clearance and lower renal NOx fractional excretion. After correction of p values for multiple comparisons, there were no significant relationships for the RA group between measures of disease activity and the urinary NOx, serum NOx, or urinary NOx clearance. Despite interest in the use of NO as a marker of disease activity, alterations in renal NOx clearance and fractional excretion in RA make it difficult to assess in vivo NO production even with strict dietary restriction of NOx intake.     

Efficacy and Safety of Linezolid in Treating Gram-Positive Bacterial Infection in the Elderly: A Retrospective Study

Linezolid is commonly used for the treatment of drug-resistant Gram-positive bacterial infection. This study aimed to evaluate the efficacy and safety of linezolid in treating Gram-positive bacterial infection in the elderly from January 2010 to December 2012. Total 40 elderly patients (>60 years old) with Gram-positive bacterial infection were treated with linezolid and their demographic and clinical data were collected and analyzed. Among the 40 patients, 31 patients (77.5 %) were cured. Linezolid caused little adverse effects on liver and renal function. The main adverse effect was thrombocytopenia and its incidence was significantly associated with baseline platelet count and the duration of treatment (P < 0.05). Logistic regression analysis showed that the baseline platelet count <200 × 10⁶/mL, but not the age, the sex, the length of hospital stay, baseline levels of hemoglobin, alanine aminotransferase, or creatinine clearance rate was significantly associated with linezolid-induced thrombocytopenia. In conclusion, linezolid is effective to cure Gram-positive bacterial infection in the elderly and causes little adverse effects on liver and renal function. Timely monitoring of baseline platelet count may be helpful to guide the use of linezolid to avoid the occurrence of thrombocytopenia.     

Intérêts et limites de l’estimation du débit de filtration glomérulaire avec des formules qui utilisent la créatinine ou la cystatine C dans une population âgée dénutrie

Renal function is often altered in elderly patients. A lot of formulae are proposed to estimate GFR to adjust drug posology. French guidelines recommend the Cockcroft-Gault formula corrected with the body surface area, but the initially described unadjusted Cockcroft-Gault equation is mainly used in geriatric clinical practice. International recommendations have proposed the modification of diet in renal disease (MDRD) formula, since several authors recommended the Rule formula using cystatin C in particular population. To appreciate the most accurate GFR estimation for posology adaptation in an elderly polypathological population, a cross-sectional study with prospective inclusion was carried out in Charles Foix Hospital. Plasma glucose levels, creatinine levels and serum cystatin C, albumin, transthyretin. C-reactive protein, orosomucoid, total cholesterol levels were determined among 193 elderly patients aged 70 and older. The results showed that in a malnourished, inflamed old population, CG, MDRD and Rule formulae resulted in different estimations of GFR, depending on nutritional and inflammatory parameters. Only cCG estimation was shown to be independent from these parameters. To conclude, cCG seems to be the most accurate and appropriate formula in a polypathological elderly population to evaluate renal function in order to adapt drug posology.     

Creatinine clearance in renal disease. A reappraisal

To determine the validity of endogenous creatinine clearance as a measure of glomerular filtration rate in patients with renal disease 308 simultaneous determinations of inulin clearance and endogenous creatinine clearance were reviewed and analysed. The ratio of creatinine clearance/inulin clearance increased progressively with the decline in inulin clearance, while the finding of a normal endogenous creatinine clearance masked a definite but mild decrease of glomerular filtration rate in 42% of the patients and a moderate decrease of glomerular filtration rate in 23%. This indicates that with declining glomerular filtration rates the endogenous creatinine clearance progressively overestimates actual glomerular filtration rates. Hence a single determination of creatinine clearance can be misleading as a screening measurement of glomerular filtration rate.     

Serum digoxin in patients with thyroid disease.

Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease.     

老年ST段抬高型心肌梗死后发生恶性室性心律失常的危险因素分析

目的:探讨老年ST段抬高型心肌梗死患者发生恶性室性心律失常的相关危险因素。方法:对150例老年ST段抬高型心肌梗死患者的临床资料进行回顾性分析,根据有无恶性室性心律失常(MVA)将其分为对照组(非MVA)和观察组(MVA),对两组的临床资料及指标进行比较,并进行Logistic回归分析。结果:性别、年龄、吸烟史、高血压史、糖尿病史、心绞痛史、血糖、糖化血红蛋白(Hb A1c)、血钾、肌酐(Cr)、BUN、甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)及病变类型与老年ST段抬高型心肌梗死患者发生MVA的发生无关,Killip分级、Cr和LDL与MVA的发生有关,且Killip分级和Cr水平是发生MVA的独立危险因素。结论:Killip分级和Cr水平是诱发老年ST段抬高型心肌梗死后MVA的独立危险因素。     

MicroRNA-34a suppresses invasion and metastatic in esophageal squamous cell carcinoma by regulating CD44

Cisplatin is a widely used antineoplastic agent in the treatment of head and neck cancer. However, it is highly nephrotoxic. Oxidative stress is the main mechanism responsible for cisplatin-induced nephrotoxicity. The aim of this study was to characterize cisplatin-induced nephrotoxicity, oxidative stress in peripheral blood mononuclear cells, and the relationship between them. Twenty-four patients were included in the study. Patients had their blood collected prior to cisplatin administration, and 5 and 20 days after initiating therapy, to assess renal function and to determine oxidative stress with MitoSOX?Red, H₂DCF-DA, and Amplex^® Red tests. Renal function was assessed by measuring serum creatinine, creatinine clearance, and blood urea nitrogen (BUN). Serum creatinine and creatinine clearance were used to grade nephrotoxicity using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Compared to baseline values, the mean BUN and serum creatinine increased 135 and 100%, respectively, 5 days after cisplatin infusion. Mean creatinine clearance showed a 43% decrease compared to baseline value. Non-statistically significant changes in superoxide anion (O ₂ ^?? ), hydrogen peroxide (H₂O₂), and general reactive oxygen species production occurred. A higher production of H₂O₂ was correlated with variation in serum creatinine, and was associated with higher grades for serum creatinine increases and creatinine clearance reductions. Linear regression analyses showed an association between H₂O₂ production and serum creatinine, creatinine clearance, and BUN levels. These results were observed for 5 days following cisplatin administration. In conclusion, H₂O₂ production was significantly related to changes in all renal parameters that were evaluated, following the cisplatin infusion.     

Renal function after long-term treatment with lithium.

Daily urine volumes, plasma creatinine concentrations, and creatinine clearance were measured in 106 patients with unipolar and bipolar affective disorders attending a "lithium" clinic. Urine volumes exceeded 3.51 in only six patients, plasma creatinine concentrations exceeded 150 mumol/1 (1.7 mg/100 ml) in only five, and creatinine clearance was below 50 ml/min in 16. Renal function was assessed by measuring creatinine clearance and renal tubular function, including response to 20 hours of water deprivation, in a representative sample of 30 patients from the lithium clinic and 30 psychiatric patients matched for age and sex who were taking other psychotropic drugs. Creatinine clearance and tubular function, including urine osmolality after water deprivation, were not significantly different between the two groups. Urinary excretion of arginine vasopressin (AVP), however, was much greater in the lithium-treated patients, who therefore had a diminished tubular responsiveness to AVP. The findings do not support suggestions that long-term lithium treatment results in seriously impaired renal function, renal damage, and polyuria. Compared with other series, however, the patients were being maintained with low serum lithium concentrations, which apparently area as effective prophylactically as higher concentrations.     

Role of the kidney in the metabolism of apolipoprotein A-IV: influence of the type of proteinuria

Increased plasma concentrations of apolipoprotein A-IV (apoA-IV) in chronic renal disease suggest a metabolic role of the kidney for this antiatherogenic protein. Therefore, we investigated patients with various forms of proteinuria and found increased serum concentrations of apoA-IV in 124 nephrotic patients compared with 274 controls (mean 21.9 +/- 9.6 vs. 14.4 +/- 4.0 mg/dl; P < 0.001). Decreasing creatinine clearance showed a strong association with increasing apoA-IV levels. However, serum albumin levels significantly modulated apoA-IV levels in patients with low creatinine clearance, resulting in lower levels of apoA-IV in patients with low compared with high albumin levels (21.4 +/- 8.6 vs. 29.2 +/- 8.4 mg/dl; P = 0.0007). Furthermore, we investigated urinary apoA-IV levels in an additional 66 patients with a wide variety of proteinuria and 30 controls. Especially patients with a tubular type of proteinuria had significantly higher amounts of apoA-IV in urine than those with a pure glomerular type of proteinuria and controls (median 45, 14, and 0.6 ng/mg creatinine, respectively). We confirmed these results in affected members of a family with Dent's disease, who are characterized by an inherited protein reabsorption defect of the proximal tubular system. In summary, our data demonstrate that the increase of apoA-IV caused by renal impairment is significantly modulated by low levels of serum albumin as a measure for the severity of the nephrotic syndrome. From this investigation of apoA-IV in urine as well as earlier immunohistochemical studies, we conclude that apoA-IV is filtered through the normal glomerulus and is subsequently reabsorbed mainly by proximal tubular cells.