Summary. After acute administration of ammonium chloride, infants 1 to 16 months of age were similar to older children in their capacity to acidify their urine. The infants had a higher rate of excretion of titratable acid and a lower rate of excretion of ammonium but were similar in their rate of excretion of total hydrogen ion.Bicarbonate titrations performed in infants during the first year of life demonstrated a threshold ranging from 21.5 to 22.5 mmoles per L, maximal rate of reabsorption from 2.6 to 2.9 mmoles per 100 ml glomerular filtrate, and marked titration splay. A nephronic frequency distribution curve of the ratio of glomerular filtration rate to tubular reabsorptive capacity demonstrated both heterogeneity and skewing to the right, suggesting the presence of significant numbers of nephrons with low tubular transport capacity relative to filtration rate.

ExtractThe present observations were undertaken to establish the response of children to the acute administration of ammonium chloride, in order to provide a basis for identifying and interpreting abnormalities in the mechanisms involved in renal acid base regulation. Fifty-eight normal children aged 4 to 13 years were studied before and for 5 hours following administration of ammonium chloride. Group A, consisting of 23 children, received 75 mEq/m2 body surface area or 2.75 mEq/kg body weight. Group B, consisting of 35 children, received 150 mEq/mZ, or 5.45 mEq/kg.Values for serum electrolytes, urea, creatinine, osmolality and acid-base parameters in children in Groups A and B are shown in tables I and 111. Urinary pH and rates of excretion of titratable acid and ammonium are shown in tables I1 and IV. The relations between blood tCO, and urinary concentration of H+, rate of excretion of titratable acid, and rate of excretion of ammonium for all subjects are shown in figures 1-3. Progressively lower values of pH were observed over the entire range of tCO, studied. During control periods, an inverse correlation was present between tCO, and rates of excretion of both titratable acid and ammonium. At levels of tCO, below 22.5 mmoles/l, the rate of excretion of TA and ammonium became constant, with mean rates of excretion of 52 pEqlminl 1.73 m2 (range, f 2 SD, 33 to 71), and 73 pEqlminll.73 m2 (46 to loo), respectively.These data are interpreted as demonstrating the importance of the blood tCO, or, more precisely, the concentratibn of bicarbonate in glomerular filtrate in urinary acidification mechanisms as well as in control of excretion of bicarbonate. Assessment of renal acidifying mechanisms requires administration of sufficient ammonium chloride or other acidifying substance to depress blood tCO, to levels well below the renal threshold.The physiologic validity of the hydrogen ion clearance index must be questioned, since correcting rates of excretion of hydrogen ion for concentration of total CO, in blood presumes that there is a fixed relation between these two measurements. In figure 4, urinary excretion of total hydrogen ion is plotted as a function of blood tCO,. Hydrogen ion excretion, negligible at tCO, levels of 26 or more, increases steadily as tCO, falls to values below the threshold. The rate of excretion then reaches maximal levels, despite further reduction in blood tCO,. Thus, the hydrogen ion clearance index is valid only over the range of blood tCO, in which there is a linear relationship with rate of excretion of hydrogen ion. Renal acidification mechanisms should be evaluated with blood tCO, several millimoles below the threshold, assuring a maximal response and permitting direct comparison with normals. In subjects with a normal bicarbonate threshold, blood tCO, should be depressed at least to 17-18 mmoles/l in infants and 20-21 mmoles/l in older children. If an abnormal bicarbonate threshold is present the dose must be adjusted accordingly. SpeculationThese studies suggest that both the con...

ExtractThisreport concerns two patients with primary renal tubular acidosis (RTA) in whom the abnormality in hydrogen excretion was shown to result from inappropriate urinary loss of bicarbonate due to a low renal hicarbonate threshold. O n the basis of the findings, a new definition and reclassification of RTA is proposed.. .The clinical course and response to medication is illustrated in figs. 1-4. Repeated measurements of clearances of creatinine, inulin, and PAH gave normal values (table I).Excretion of aminoacids (table 11) was normal in both patients. After water restriction, the urinary osmolality was 990 mOsm/kg water for K. J. and 1088 mOsm/kg water for S.G. No reducing substance was found in the urine of K. J. ; glucose was present in trace amounts on several occasions in the urine of S.G. Tul~ular real~sorption of phosphate was always in the normal range, 80 to 90 percent of the filtered amount. Both children had an adequate response to the oral administration of ammonium chloride, providing no alkali therapy was being administered at the time of the test (table 111).In fig. 5, rates of reabsorption and excretion of bicarbonate, expressed as mmoles/100 ml glomerular filtrate (GF) are plotted against serum bicarbonate concentration in mmoles/liter. Data from 2 studies are included in the figure. K. J. started to excrete bicarbonate into the urine at a serum bicarbonate level of 18 to 19 mmoles/liter; the T m of reabsorption was low, being approximately 2.1 mmoles/100 ml GF. In S.G., although the threshold was similarly depressed (19 to 20 mmoles/liter), the T m of reabsorption was at the lower limit of the normal range (2.5 to 2.6 mmoles/100 ml GF).The ratio of reabsorbed bicarbonate to T m has been plotted as a function of the ratio of filtered l~icarbonate to T m ( fig. 6). The data from the studies in K. J. demonstrate a splay very similar to that of normal infants. S.G., however, has a markedly increased splay. During bicarbonate infusion and when rates of bicarbonate reabsorption were near the Tm, acetazolamide was administered intravenously in a single dose of 100 mg. In both children, marked inhibition of bicarbonate reabsorption was demonstrated. At similar rates offiltered bicarbonate, the urinary excretion increased two-to-three-fold with a concomitant decrease in the rate ofreabsorption (table V).Results for glucose reabsorption in K.J. are close to those of normal adults with a threshold of 300 mg/min/1.73 m2 and a T m of over 400. In contrast, S.G. had small amounts of glucose in the control urines and the glucose threshold was abnormally low, approximately 100 mgImin11.73 m2. Although blood glucose was not maintained at high values long enough to be certain that the T m had been reached, values as high as 327 mg/min/1.73 m2 were obtained, suggesting that his glucose T m was normal.After administration of histamine, the acidity of the gastric fluid increased markedly and the values of free acid and total titratable acid compare closely with that of normal children (table VI).Histologic exa...

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