Carlos A. Vaamonde

Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis

BACKGROUND Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level. METHODS In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration. RESULTS For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild. CONCLUSIONS In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Renal handling of sodium and water in the hypothyroid rat: Clearance and micropuncture studies

Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals. Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P](IN)) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats. These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron.

Renal acidosis and renal potassium handling in selective hypoaldosteronism

Abstract Selective hypoaldosteronism was demonstrated in a 60 year old black man with moderate renal insufficiency and hyperkalemic, hyperchloremic acidosis. Urine pH was appropriately low during acid loading demonstrating that the hydrogen ion gradient generating capability of the distal-most nephron was intact. In addition to impaired net acid excretion during acidosis, significant bicarbonaturia was present when serum bicarbonate concentration was normal. Desoxycorticosterone acetate (DOCA) administration improved renal potassium handling and corrected the hyperkalemia but not the acidosis or bicarbonaturia. It is concluded that the patient had idiopathic selective hypoaldosteronism and hyporeninemia and that the hyperkalemia was related to hypoaldosteronism. The patients bicarbonaturia, however, did not appear to be related to mineralocorticoid deficiency and therefore should be attributed to other factors.

Impaired renal concentrating ability in hypothyroid man.

The renal concentrating ability was studied in ten patients with hypothyroidism and in 15 euthyroid controls. Solute-free water reabsorption was reduced in the patients with myxedema (4.2 +/- 0.3 ml/min: controls 5.8 +/- 0.6 ml/min; p less than 0.01). This defect was apparent at high rates of solute excretion, and was associated with enhanced excretion of sodium (p less than 0.01) despite a decreased filtered load (p less than 0.005). The myxedema patients had a modest reduction in maximal urine osmolality (p less than 0.04), which was entirely attributable to the lower values observed in younger patients. The results may be explained best by decreased sodium chloride reabsorption in the ascending limb of Henles loop and/or diminished permeability of the distal nephron in myxedema.

Renal failure in cirrhosis--role of plasma volume.

Excerpt Many investigators have demonstrated the occurrence of spontaneous, unexplained renal failure in patients with cirrhosis (1, 2). Patients with this syndrome are usually, but not necessarily...

Psoriasis during hemodialysis.

Abstract To the editor: Recent uncontrolled trials of dialytic therapy of psoriasis suggest a remarkable clinical improvement (1-3). However, this disease may manifest spontaneous improvements and ...

Renal Excretion of Sodium During Oral Water Loading in Man

The renal excretion of sodium following an oral sustained 20 ml/kg water load was studied in 10 normal volunteers and in 13 patients without evidence of renal, hepatic, cardiovascular or endocrine disease. The study was performed under conditions controlled for sodium content of the diet, time of the day and posture. Under the described conditions the diuresis following the administration of an oral water load was not accompanied by enhanced excretion of sodium. Sodium excretion was also studied in nine normal volunteers given an oral sustained 10 ml/kg water load and ethyl alcohol. Sodium excretion did not increase with increasing flow.

Renal Excretion of Sodium During Oral Water Administration in Patients with Systemic Hypertension

The renal excretion of sodium and water was studied in 10 hypertensive subjects following an oral sustained 20 ml/kg water load. The study was performed under conditions controlled for sodium content of the diet, time of the day, and posture; the urine was collected by spontaneous voiding. The results were compared with those obtained from 10 normotensive subjects studied under similar conditions.The increased urine flow following the water load in the hypertensive subjects was not accompanied by increased excretion of sodium, a pattern similar to the one observed in the normotensive subjects.Comparing the group of hypertensive subjects with previously studied normotensives revealed the following additional information. The hypertensive subjects responded to water administration by increasing volume and CH2O more rapidly than the normotensives; however, the maximal response was not significantly different. The fractional reabsorption of sodium was less in the hypertensive subjects despite a lower filtered load of sodium. This suggests a difference in the renal tubular handling of sodium between hypertensive and normotensive subjects.