Removal of an inorganic acid load in subjects with ketoacidosis of chronic fasting.

When a large inorganic acid load is ingested by normals, the proton load is eliminated because the rate of excretion of ammonium can rise to 200 to 300 mmol/day. In subjects with ketoacidosis of chronic fasting, such a large increase in the rate of excretion of ammonium might not be possible because of ATP balance considerations in proximal cells. Subjects with ketoacidosis of chronic fasting excreted less net acid as defined in the conventional way when they consumed a large inorganic acid load (136 +/- 6 vs. 176 +/- 26 mmol/day in control fasted subjects). Nevertheless, the vast majority of this inorganic acid load was eliminated because they were in steady state and had only a slightly lower concentration of bicarbonate (13 +/- 0.6 vs. 15 +/- 0.5 mmol/liter) and ketoacid anions (3.3 +/- 0.2 vs. 5.5 +/- 0.2 mmol/liter) in their blood. Using a definition of net acid excretion where the component of bicarbonate loss was expanded to include "potential bicarbonate" (ketoacid anions) in the urine, the rate of excretion of net acid was higher in subjects who ingested the inorganic acid load, owing to a much lower rate of excretion of ketoacid anions (9 +/- 2 vs. 120 +/- 7 mmol/day). This lower rate of excretion was not only due to a lower filtered load, but also to a higher fractional reabsorption of ketoacid anions during acidosis (97 +/- 0.1 vs. 77 +/- 0.2%). This higher fractional reabsorption could not be explained by a lower filtered load of ketoacid anions or to a restricted intake of sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of subclavian catheters for hemodialysis.

In 98 patients, we cannulated the subclavian and internal jugular veins with modified Shaldon catheters, using the Seldinger technic. Catheters were left for long periods, and multiple dialyses were accomplished with each catheter. The incidence of major complications was less than 5%. None of the catheters were believed to be the cause of any clinically significant infection. This technic proved to be a safe, convenient, and inexpensive method for providing rapid vascular access for hemodialysis.

The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer.

The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.

Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis.

An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency.

Unusual fractures during convulsions in two patients with renal osteodystrophy.

Two men undergoing chronic hemodialysis sustained unusual fractures during grand mal convulsions. Both patients showed radiologic evidence of renal osteodystrophy. In one, the fractures involved both femoral necks. In the other, a comminuted fracture occurred in the inferior portion of the left scapula.

Mechanism by which neutral phosphate infusion elevates urine PCO2.

Currently, the ability to elevate the urine PCO2 above that of the arterial blood is employed as an estimate of distal hydrogen ion secretion. Therefore, it is important to establish the mechanisms by which various factors affect the urine CO2 tension. This paper examines the physiologic process by which phosphate elevates the urine PCO2 in the dog. The rise in urine PCO2 due to phosphate could be the result of either (1) a distal mechanism, by affecting the delayed dehydration of carbonic acid, or (2) an increase in the medullary PCO2. The phosphate-induced elevation of urine PCO2 was abolished by carbonic anhydrase infusion. This indicates that a distal mechanism is a major factor in the phosphate effect. Since acid phosphate infusion did not result in an elevated urine PCO2, it is unlikely that changes in the medullary PCO2 occur as a ry an increase in net acid excretion, indicating an increase in hydrogen ion secretion. The increased hydrogen ion secretion and rise in urine PCO2 were reproduced by infusion of the buffer, Tris-(hydroxymethyl)-aminomethane, but not by sodium sulfate administration. These findings suggest that the phosphate-induced rise in urine PCO2 is due to the buffer properties of phosphate rather than to its nonreabsorable anion characteristics.

Renal localization of antiglobulins in glomerulonephritis and after renal transplantation.

Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.

Effect of amphotercin B on urine acidification in rats: implications for the pathogenesis of distal renal tubular acidosis.

It has been proposed that distal renal tubular acidosis is a gradient-limited disorder an that the low urine Pco2 observed in this condition is caused by back diffusion of carbonic acid. This study was designed to examine this hypothesis using the amphotericin B model of gradient-limited distal renal tubular acidosis in rats. After induction of acute metabolic acidosis the minimum urine pH in 12 of 24 amphotericin B-treated rats exceeded 5.63 (mean 5.76 +/- 0.04), whereas it was 5.41 +/-0.04 in control rats. These animals with impaired urine acidification were presumed to have a gradient lesion and were studied in bicarbonate-loading experiments. The urine minus blood Pco2 gradient in these rats was 24.9 +/- 1.5 mm. Hg, a value similar to that of the control rats (26.7 +/- 2.1 mm. Hg). The presence of a normal urine minus blood Pco2 value in this experimentally induced gradient-limited type of acidification lesion indicates that a permeability defect for hydrogen ions was not associated with a similar defect for carbonic acid and that the urine minus blood Pco2 gradient is a valid index of distal nephron hydrogen ion secretion in amphotericin B-like gradient-type lesions.

Lack of dependence of urine PCO2 upon reduction of glomerular filtration rate in alkalotic dogs.

1. The PCO2 gradient between alkaline urine and arterial blood (U-B PCO2) is thought to depend primarily on distal hydrogen ion secretion. However, other variables affecting the U-B PCO2 include the urine flow rate, the urinary bicarbonate and phosphate excretion rates and the glomerular filtration rate. 2. In order to evaluate the effects of acute changes in these factors on the U-B PCO2, bicarbonate-loaded dogs with maximal U-B PCO2 values were subjected to either acute unilateral elevations of ureteral pressure or hypotension caused by nitroprusside infusion. The results demonstrate that acute reduction in the glomerular filtration rate does not cause a decrease in the U-B PCO2 as long as the urinary concentrations of phosphate and bicarbonate do not decline. 3. Urinary concentrations of phosphate and bicarbonate appeared more important than their excretion rates in the maintenance of elevated U-B PCO2 values.

Soluble immune complexes in sera of patients with nephritis.

Binding of radioactively labeled C1q was used to detect soluble antigen-antibody complexes in sera collected at the time of renal biopsy from 104 patients with immunofluorescent findings consistent with immune-complex disease. In comparison with data obtained with sera from 85 healthy donors, significantly elevated C1q binding activity was demonstrated in sera from 22 patients. C1q binding was elevated in all four patients whose dominant histologic finding on bright field microscopy was an intense interstitial mononuclear cell infiltrate. High C1q binding activity was found preferentially in sera from patients who had diffuse rather than focal histologic abnormalities by light microscopy, heavy glomerular deposits of C4 and C3 by immunofluorescence and elevated serum creatinine concentrations. However, there were many patients with similar immunofluorescent and bright field microscopic changes in whom circulating complexes were not detected and there was no correlation between the pattern of glomerular localization of immune complexes and the C1q binding activity of the sera. Serial measurements of C1q binding activity in the sera from three patients over a 90-day interval emphasized that immune complexes may be demonstrated by this technique only intermittently in the sera of some patients with renal biopsy evidence of immune-complex disease. Nevertheless, these observations suggest that the C1q binding test may be a useful tool to monitor disease activity in patients with immunologically mediated renal disease.

Antiglobulins and glomerulonephritis. Classification of patients by the reactivity of their sera and renal tissue with aggregated and native human IgG.

Renal biopsies and sera from 41 consecutive patients were studied to determine if antiglobulins were found more frequently in patients with severely diseased glomeruli. Patients were classified into three groups: A, 12 patients with normal renal function and minimal histological evidence of glomerular disease; B, 18 patients with normal renal function but distinctly abnormal biopsies (16 cases) or proteinuria greater than 16 g/24 h (2 cases); and C, 11 patients with both decreased function and abnormal histology. Positive latex fixation tests for rheumatoid factor were found in none of group A, four (22%) of group B, and five (45%) of group C patients. Sera heated 56 degrees C for 30 min contained precipitins reactive with heat-aggregated IgG in none of seven group A, five of ten (50%) group B, and four of ten (40%) group C patients. The quantity of 135I-labeled patient globulin which bound to immunoadsorbents coated with Cohn fraction II in competition with an equal quantity of 131I-labeled globulin from pooled plasma of normal donors was also measured. Patient globulins bound in significantly greater quantity (greater than or equal 2 SD) than the control in none of the group A, 7 of 18 (39%) group B, and 7 of 11 (64%) group C patients. Renal biopsies from 18 patients were also studied for the ability to fix fluorescein-conjugated heat-aggregated and native human IgG. None of nine tissue specimens from group A or B patients fixed either fluorescein-conjugated protein whereas tissue from eight of nine group C patients showed glomerular localization of one or both reagents. Severity of disease as judged by renal function and glomerular histology correlated with the presence of tissue-fixed and serum antiglobulins. Thus, detection of antiglobulins in glomeruli and sera of patients with glomerulonephritis may indicate a relatively poor prognosis and raises the possibility that antiglobulins may be implicated in some way in the pathophysiology of human glomerulonephritis.

Taste thresholds for salt in fasting patients.

Since it has been controversial whether in man changes in taste sensitivity for salt occur in relation to changes in extracellular volume, as has been described in animals, we assessed saline acuity in human volunteers undergoing a predictable pattern of external sodium balance. Our results demonstrate that taste thresholds for salt did not vary despite oppositely directed changes in renal sodium excretion and sodium balance.

Mechanism for the paradoxical aciduria following alkali administration to prolonged-fasted patients.

Rapidly induced systemic alkalinization due to either sodium-lactate or sodium-bicarbonate infusion in prolonged-fasted subjects with steady-state ketoacidosis was associated with a decrease in urine pH. This decrease in urine pH from 5.50 to 5.20 was the result of a significant decrease in urinary ammonium excretion from 8.40 to 6.35 mEg/hr and was not accompanied by an increase in net acid excretion (11.3 vs. 10.6 mEg/hr). The decreased ammonium excretion is attributed to the raised pH of the proximal tubular fluid resulting in a less favorable pH gradient for gaseous ammonia entry. This would decrease gaseous ammonia generated in the loop of Henle for collecting duct buffering of secreted hydrogen ions.

Glucose-induced alkalosis in fasting subjects. Relationship to renal bicarbonate reabsorption during fasting and refeeding.

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.