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Two papers, one in 1986 and another one in 1988, reported a strong inverse correlation between urinary anion gap (UAG) and urine ammonia excretion (UNH(4)) in patients with metabolic acidosis and postulated that UAG could be used as an indirect measure of UNH(4). This postulation has persisted until now and is widely accepted. In this review, we discuss factors regulating UAG and examine published evidence to uncover errors in the postulate and the design of the original studies. The essential fact is that, in the steady state, UAG reflects intake of Na, K, and Cl. Discrepancy between intake and urinary output of these electrolytes (i.e., UAG) indicates selective extrarenal loss of these electrolytes or nonsteady state. UNH(4) excretion, which depends, in the absence of renal dysfunction, mainly on the daily acid load, has no consistent relationship to UAG either theoretically or in reality. Any correlation between UAG and UNH(4), when observed, was a fortuitous correlation and cannot be extrapolated to other situations. Furthermore, the normal value of UAG has greatly increased over the past few decades, mainly due to increases in dietary intake of potassium and widespread use of sodium salts with anions other than chloride as food additives. The higher normal values of UAG must be taken into consideration in interpreting UAG.

L-lactic acidosis (L-LA) is the most common cause of metabolic acidosis in the critical care setting, which has been associated with a large increase in mortality. The purpose of this article is to provide clinicians with an overview of the biochemical and metabolic background required to understand the different pathophysiological mechanisms that may lead to the development of L-LA. We propose a classification based on whether the pathophysiology of L-LA is due predominantly to increased production or decreased removal of L-lactic acid. In this article, we provide an overview of the biochemical and metabolic aspects of glucose oxidation, the production and removal of L-lactic acid, and a discussion of the pathophysiology of the various causes of L-LA.

The dialysate alkali used in hemodialysis to replace low body alkali levels in end stage renal disease (ESRD) patients has changed over time from bicarbonate to acetate and finally back to bicarbonate with a small addition of acetate. The ideal way to replace alkali in dialysis patients remains uncertain. Elsewhere in this issue of the journal, Sargent and Gennari, who have contributed greatly to our understanding of dialysis and acid-base kinetics, suggest that decreasing the currently used concentration of bicarbonate while increasing concentration of acetate in the dialysate may be a much more physiological approach to alkali delivery during hemodialysis. These recommendations are based on results from a series of hemodialysis simulations using mathematical theoretical methods, with the assumption that acetate metabolism will be sufficiently delayed with the higher acetate dialysate and reduce the rate of correction of metabolic acidosis during dialysis. Although valuable in calling attention to the issues surrounding alkali repletion during hemodialysis, these postulations should be tested in clinical trials. We believe, however, that the available evidence suggests that the rate of gain of bicarbonate during dialysis with the higher acetate dialysate would not be slower and that the replacement of some dialysate bicarbonate with acetate will not alter alkali accretion or intradialytic pH.

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

Our goal is to suggest how the renal concentrating mechanism is regulated in vivo.The majority of descending thin limbs of the loop of Henle lack aquaporin-1 water channels, and loops of Henle in the inner medulla lack urea transporters.Lack of water permeability in the descending thin limbs of the loop of Henle offers several advantages. First, since much less water is added to the outer medullary interstitial compartment, inhibitory control mechanisms on sodium and chloride reabsorption from the medullary thick ascending of loop of Henle initiated by water addition from the medullary collecting duct can be effective. Second, recycling of urea is efficient, as little urea will be washed out of the medulla. Third, delivery of a larger volume of filtrate to the medullary thick ascending limb of the loop of Henle permits both an appreciable reabsorption of sodium along with only a small fall in the luminal concentration of sodium in each of these liters. Hence there need be only a small lumen positive voltage in the medullary thick ascending limb of the loop of Henle. The absence of urea transporters in the loop of Henle in the inner medulla is required for a passive mechanism of sodium and chloride reabsorption in the inner medulla. Control of urea reabsorption from the medullary collecting duct is needed to prevent excessive oliguria in electrolyte-poor urine.

Hyponatremia, the most common electrolyte disorder in hospitalized patients, has been associated with high rate of mortality among both this population and nonhospitalized patients. This review describes briefly the classification and pathogenesis of hyponatremia, and, in greater detail, the management of hyponatremia with a particular emphasis on the clinical pharmacology of arginine vasopressin (AVP) antagonists. This review includes more in-depth discussion on the pharmacology of conivaptan, an AVP antagonist recently approved by the United States Food and Drug Administration.

In vitro, experimental, and clinical work suggests that metabolic acidosis, either directly or indirectly, can promote the progression of chronic kidney disease (CKD). Goraya et al. demonstrate that both oral alkali supplementation and a diet rich in fruits and vegetables are equally effective at decreasing urinary excretion of markers of renal injury in patients with stage 2 CKD. Although this study is promising, the short duration and use of only urinary markers as a surrogate outcome weaken the conclusions.

Item does not contain fulltext A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotransporter; one of these mutations is newly described. Her clinical findings were not typical because of the absence of hypocalciuria in 24-h urine samples, her maximum urine osmolality (U(osm)) was only 802 mosmol/kg H(2)O, and her plasma magnesium (Mg) concentration (P(Mg)) was easily maintained in the normal range with oral Mg supplements for 1 month. In detailed studies, the calcium/creatinine ratio in spot urines with a U(osm) >700 mosmol/kg H(2)O was very low, except during Mg therapy. Renal medullary function did not appear to be compromised because she had a non-urea U(osm)of approximately 600 mosmol/kg H(2)O, reflecting a very high non-urea osmole excretion rate (due to KCl supplements). At age 18 years, her P(Mg) became persistently low despite Mg therapy. We conclude that the clinical criteria for a provisional diagnosis of Gitelman syndrome should be revised. Hypocalciuria may only be evident initially in concentrated spot urine samples. Urine concentrating ability should include an analysis of the non-urea U(osm), especially when patients are taking large KCl supplements.

Two aspects of hypernatremia are emphasized in this discussion: pathogenesis and treatment. Hypernatremia rarely develops with increased water loss alone; there must be a mechanism that interferes with water intake. In treating hypernatremia, the speed of correction is important because the volume regulation mechanisms restore the brain volume to normal when hypernatremia is chronic. Thus, too rapid correction of chronic hypernatremia results in brain edema. The calculation of fluid volume needed to correct hypernatremia can be obtained with use of various formulae described here for the fluid that contains dextrose in water or for hypotonic saline solution. Accurate prediction of the fluid volume requirement demands the knowledge of urine output and its electrolyte content, but when the information is not available, urine may be assumed to be isotonic in its electrolyte content.

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders, only half of hemodialysis (HD) patients achieve recommended serum phosphate levels. A hyperphosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients. We hypothesized that binding salivary phosphate during periods of fasting in addition to using phosphate binders with meals could improve the treatment of hyperphosphatemia. We assessed the phosphate-binding capacity of the natural polymer chitosan by (31)P nuclear magnetic resonance and established that 10 and 20% (wt/vol) middle viscosity chitosan solutions bind 30 and 50% of the phosphate contained in PBS, respectively. Thirteen HD patients with serum phosphate levels6.0 mg/dl despite treatment with sevelamer hydrochloride chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 wk at fast in addition to their prescribed phosphate-binding regimen. Salivary phosphate and serum phosphate significantly decreased during the first week of chewing; by the end of 2 wk, salivary phosphate decreased 55% from baseline (73.21 +/- 19.19 to 33.19 +/- 6.53; P0.00001), and serum phosphate decreased 31% from baseline (7.60 +/- 0.91 to 5.25 +/- 0.89 mg/dl; P0.00001). Salivary phosphate returned to baseline by day 15 after discontinuing the chewing gum, whereas serum phosphate levels took 30 d to return to baseline. Parathyroid hormone and serum calcium concentrations were not affected by the gum. In conclusion, adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in HD patients.

This report describes a case of d-lactic acidosis observed by the authors and then reviews all case reports of d-lactic acidosis in the literature in order to define its clinical and biochemical features and pathogenetic mechanisms. The report also reviews the literature on metabolism of d-lactic acid in humans. The clinical presentation of d-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The diagnosis should be considered in a patient who presents with metabolic acidosis and high serum anion gap, normal lactate level, negative Acetest, short bowel syndrome or other forms of malabsorption, and characteristic neurologic findings. Development of the syndrome requires the following conditions 1) carbohydrate malabsorption with increased delivery of nutrients to the colon, 2) colonic bacterial flora of a type that produces d-lactic acid, 3) ingestion of large amounts of carbohydrate, 4) diminished colonic motility, allowing time for nutrients in the colon to undergo bacterial fermentation, and 5) impaired d-lactate metabolism. In contrast to the initial assumption that d-lactic acid is not metabolized by humans, analysis of published data shows a substantial rate of metabolism of d-lactate by normal humans. Estimates based on these data suggest that impaired metabolism of d-lactate is almost a prerequisite for the development of the syndrome.

Acid-base balance in chronic peritoneal dialysis patients. Endogenous acid production has never been measured directly in dialysis patients and an empiric formula is used to estimate acid production from their protein catabolic rate. We have studied acid-base balance in 19 stable CAPD patients attending the peritoneal dialysis clinic of Mount Sinai Hospital. They obtained a 24 hour collection of peritoneal dialysis fluid and urine while consuming their usual diet and performing their usual activities. Total alkali gain was calculated from net GI alkali absorption plus urinary net acid excretion plus alkali gain from dialysate, while total acid production was measured directly from the urinary and dialysate excretions of sulfate and organic anions. Net GI alkali absorption was estimated from the difference between cations (Na + K + Ca + Mg) and anions (Cl + 1.8P) in the 24 hour dialysate and urine collections minus the daily total amount of lactate infused. All of our patients had a normal or high serum bicarbonate concentration, which was stable with time. Total alkali gain was virtually identical to total acid production (54.2 vs. 52.4 mEq/day) which suggests that these patients were in neutral acid-base balance. Net GI alkali absorption (22.7 mEq/day) was one of the same range as that of chronic renal failure patients not on dialysis and represented almost one half of the total daily alkali gain. The daily acid production of 52.4 mEq/day was numerically equal to 84% of the protein catabolic rate expressed as g/day, which is similar to the predicted value of 77% of PCR reported in the literature. However, the main source of alkali loss, that is, acid production, was the loss of organic anions in dialysate and urine. Daily sulfate excretion (16 mEq/day) was lower than expected for the level of protein intake (protein catabolic rate of 62 g/day). The stable serum bicarbonate concentrations on long-term dialysis suggests a steady state and neutral acid-base balance in these patients. The almost perfect agreement between acid production and total alkali gain supports the validity of our methods for measuring the various parameters of acid-base balance, including net GI absorption of alkali.

Renal stone formation is uncommon in patients with type IV renal tubular acidosis (RTA). This study was undertaken to explore the urinary biochemical and physicochemical factors in patients with type IV RTA in order to elucidate the mechanisms that protect them from renal stone formation. Twelve subjects with type IV RTA and 12 matched subjects with a similar degree of kidney impairment but without RTA were studied. Both groups of patients had low urinary excretion of calcium, phosphorus, uric acid, and citrate, probably reflective of kidney impairment. Patients with type IV RTA had a significantly lower urinary pH and urinary excretion of calcium than their matched controls. Hypocitraturia was present in both groups without any significant difference between them. This study suggests that the major protection from renal stone formation in type IV RTA results from impaired renal function and ensuing reduction in renal excretion of stone-forming substances, such as calcium and uric acid.

Discussion of abnormal plasma sodium concentrations with an emphasis on the pathogenesis, diagnosis, and treatment.Relevant literature in the English language and the authors' clinical experience.No special study has been carried out for the present discussion.The information from the literature and the data from the authors' clinical experience have been used to illustrate important points in the discussion.A most important aspect in the approach to hypernatremia is determination of the mechanism responsible for impaired water intake. Various mechanisms of abnormal water loss can be determined from measurement of urine osmolality. Hypernatremia is treated by water replacement and measures to reduce abnormal water loss. In most instances, hyponatremia is caused by inappropriate concentration of urine because of either appropriate or inappropriate antidiuretic hormone secretion. The determination of appropriateness of antidiuretic hormone secretion requires the assessment of effective arterial volume. Treatment depends on the pathogenetic mechanism.Abnormal plasma sodium concentration results from abnormal water intake or water output. Treatment is guided by determining the pathogenetic mechanism.

The present communication seeks to resolve the mechanism of metabolic acidosis that persists after ketonemia has cleared; the reason for the approximate equality of excess anion gap and reduction in serum bicarbonate at the time of admission despite substantial prior urinary loss of ketone anions; the mechanism of transformation of normochloremic acidosis to hyperchloremic acidosis during the recovery phase of DKA

This discussion emphasizes two aspects of hyponatremia: classification according to effective osmolality of the body fluid, and distinction between appropriate and inappropriate ADH secretion. Assessment of the effective osmolality is important because the main deleterious effect of hyponatremia is cell overhydration, which occurs only when the effective osmolality is reduced. Since most cases of hyponatremia are associated with low effective osmolality, cell overhydration is a hallmark of acute hyponatremia. On the other hand, one must be aware of other types of hyponatremia in which effective osmolality is either normal or even increased. Inappropriateness of ADH secretion is defined as ADH secretion that occurs despite low effective osmolality and normal or expanded effective vascular volume. ADH secretion that occurs in hyponatremia is deemed appropriate if the effective vascular volume is low. The use of laboratory parameters is much more reliable in determining effective vascular volume than is careful physical examination.

The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food.

We describe a case of renal hypouricemia due to increased tubular secretion of urate associated with absorptive hypercalciuria. This association has been described in the past, but this is the first time that high plasma levels of 1,25-dihydroxyvitamin D have been reported. A possible cause-and-effect relation between altered uric acid transport and altered vitamin D metabolism in the proximal tubule is suggested.

Potassium filtered at the glomerulus is almost completely reabsorbed before the distal tubule; it must therefore be secreted into the collecting duct. The rate of potassium secretion is determined by a number of factors, notably aldosterone, distal sodium delivery, and serum potassium. Normal serum potassium is maintained by the interplay of passive leak of potassium from the cells and its active return to the cells. Transmembrane potassium distribution is influenced largely by acid-base equilibrium and hormones including insulin and catecholamines. In the diabetic with ketoacidosis hyperkalemia, in the face of potassium depletion, is attributable to reduced renal function, acidosis, release of potassium from cells due to glycogenolysis, and lack of insulin. Chronic hyperkalemia in diabetics is most often attributable to hyporeninemic hypoaldosteronism but other conditions including urinary tract obstruction may also contribute. A variety of clinical situations (e.g., volume depletion) and drugs (e.g., nonsteroidal antiinflammatory agents, and heparin) may acutely provoke hyperkalemia in susceptible individuals.

The effect of change in extracellular (interstitial) volume on vascular volume (VV) is mediated through interstitial pressure. Since the effect of swollen or shrunken cells on interstitial pressure should be identical to that of changes in interstitial volume on interstitial pressure, it would be appropriate to consider that intracellular volume (ICV) as well as extracellular volume (ECV) contributes to control of VV. Total body water rather than ECV, therefore, should be considered as the fluid volume which regulates VV. Support for these conclusions has been provided by theoretical analysis of the factors that regulate capillary fluid exchange. In further support of this hypothesis, clinical examples are described, in which renal salt retention was observed despite increase in ECV (ICV was markedly decreased), and in which renal salt loss occured despite decrease in ECV (in the presence of increased cell volume).

A group of patients whose dietary potassium was unrestricted and who received 12-18 h of Kiil dialysis twice weekly against a bath containing no potassium, had body potassium concentrations (total body potassium/intracellular volume) of 7.6% lower than normal. Despite marked hypokalemia at the end of dialysis, suprisingly few electrocardiographic changes were seen. Another group of subjects, dialyzed fro 5-6 h thrice weekly against a bath containing 1 mEq/liter of potassium in a Dow dialyzer, showed more marked electrocardiographic abnormalities despite smaller alterations in transmembrane potassium gradients. Rapidity of establishment of potassium gradients is important as well as magnitude. The following changes occur in a single dialysis: 100 mEq of cell potassium and 20 mEq of extracellular potassium leave the body; 100 mEq of extracellular sodium enter the cells and 415 mEq of extracellular sodium leave the body; 3.5 liters of water leave the extracellular fluid, 2.5 liters into the bath and 1 liter into the cells.

A 77-year-old diabetic man with a creatinine clearance of 23--27 ml/min developed hyperkalemia while receiving heparin for peripheral arterial insufficiency. Discontinuation of this agent led to resolution of hyperkalemia as the plasma aldosterone concentration multiplied by sixfold. Renal insufficiency may have predisposed this patient to the development of hyperkalemia when heparin therapy suppressed aldosterone synthesis.

A re-evaluation of the urinary parameters of acid production and excretion in patients with chronic renal acidosis. We have studied acid-base balance in 32 patients attending the renal clinic of Mount Sinai Hospital. The parameters of acid-base balance measured included acid production measured as urinary sulfate and organic anions, net acid excretion measured as urinary ammonia plus titratable acid minus bicarbonate, and net GI absorption of alkali measured by a new method utilizing urinary electrolytes. Net GI absorption of alkali by urinary electrolytes measures alkali addition to the body from the GI tract as well as from any other sources, including bone. All patients had a creatinine clearance less than 80ml/min and they were divided into two groups: those with normal serum bicarbonate (Group 1; N = 12) and those with subnormal serum bicarbonate (Group 2; N = 20). Hydrogen ion balance was -0.6 ± 9 mEq/day in the first group, while those in the second group had a hydrogen ion balance of +16 ± 5 mEq/day. A group of 8 normal controls had a hydrogen ion balance of -0.3 ± 5 mEq/day. When the sum of all cations was compared with the sum of all anions in the urine, a cation gap of exactly the same magnitude as the positive hydrogen ion balance was found in patients with low serum bicarbonate. In conclusion, our data show that patients with decreased GFR and low serum bicarbonate appear to have a significantly positive hydrogen ion balance. However, we believe that the positive hydrogen ion balance is only apparent, but not real for the following reasons. If the positive hydrogen balance shown by the previous investigators were due to bone buffering, the positive balance should have disappeared in our study since we included the contribution of bone buffers in the calculation of acid-base balance. Moreover, the positive hydrogen ion balance in our study would indicate the presence of a cation gap, a theoretical impossibility. The most likely explanation for the apparently positive hydrogen ion balance, shown only in the low bicarbonate group, is a systematic technical error in the current methods for measurement of parameters of acid-base balance, either an underestimation of net acid excretion or an overestimation of acid production. Further studies are needed to delineate the sources of technical errors.

Le taux de synthese des acides endogenes est estime par le taux d'excretion urinaire de leurs anions. De la meme facon, l'alimentation contient des alcalins, dont l'absorption au niveau du tractus gastro-intestinal est estimee par la production nulle d'acide. Traditionnellement, pour estimer les alcalins absorbes a partir de l'alimentation est realisee une comparaison entre le contenu de l'alimentation et des selles. Les problemes rencontres sont lies au temps de recueil des selles, et a leur inhomogeneite. Apres analyse de la litterature est proposee une methode d'analyse des urines. Les resultats obtenus sont bien correles a ceux obtenus par la methode traditionnelle d'analyse des selles, et semblent utilisables meme en periode de metabolisme instable

A 56-year-old woman received a kidney transplant and presented subsequently with evidence of volume contraction, hyponatremia and hyperkalemia. Urinary sodium excretion was inappropriately high for the degree of volume contraction and urinary potassium excretion inappropriately low for the degree of hyperkalemia. Marked elevation of plasma renin activity and plasma aldosterone suggested that the renal tubules were unresponsive to mineralocorticoids. The defect was shown to be transient. The mechanisms leading to the defect are discussed.

To determine the mechanism of hyperchloremic acidosis during recovery from diabetic ketoacidosis (DKA), serial measurements were made in eight patients of serum and urinary electrolytes and organic acids, and of urinary net acid. On admission, the average decrease in serum total CO2 was 17.5 mmol/L, corresponding to the excess anion gap, 18.5 meq/L, and the serum organic acids, 17.1 meq/L. With the treatment, the anion gap and organic acids decreased by 16.1 and 14.7 meq/L, respectively, but the serum CO2 increased only by 8.4 mmol/L; serum electrolyte balance was maintained by increase in chloride concentration. Fluid retention was insufficient to explain the disparity between the increase in CO2 and the decrease in organic acids. Renal loss of bicarbonate precursors during treatment was modest and was exceeded by renal bicarbonate production. The disparity between the increase in serum CO2 and the decrease in organic acids during treatment of DKA may be explained to a large extent by a difference in volume of distribution between bicarbonate and organic anions The renal loss of ketone anions before admission, however, is ultimately responsible for the persistence of substantial metabolic acidosis.

This study was carried out to investigate the renal handing of d- and l-lactate and the extent of their metabolism in men. Ten healthy male subjects were given an intravenous (IV) infusion of a racemic mixture of d- and l-lactate. At an infusion rate of 1.0 to 1.3 meq/kg body weight of each isomer, d-lactate achieved a concentration in plasma of 1.7 to 3.0 meq/L, and l-lactate 2.8 to 4.2 meq/L. At these levels, fractional excretion of d-lactate ranged from 40% to 65%, while fractional excretion of l-lactate was always less than 5%. At a higher infusion rate, 1.8 to 2.0 meq/kg/h, plasma concentrations of d- and l-lactate reached 4.5 to 6.0 meq/L, and 4.0 to 6.7 meq/L, respectively. Fractional excretion of d-lactate then ranged from 61% to 100%, while that of l-lactate ranged from 9% to 30%. At plasma concentrations of d-lactate less than 3.0 meq/L, reabsorption of l-lactate was nearly complete, but when plasma d-lactate exceeded 3.0 meq/L, reabsorption of l-lactate was considerably impaired. Similarly, for a given concentration of plasma d-lactate, its reabsorption was more efficient when the plasma l-lactate concentration and fractional excretion of l-lactate were low than when they were high. At an infusion rate of d-lactate of 1.0 to 1.3 meq/L, about 90% of the infused lactate was metabolized, and at a higher infusion rate, still more than 75% of the infused lactate was metabolized. The findings indicate that both 1- and d-lactate mutually interfere with their renal tubular reabsorption, and that reabsorption of l-lactate is much more efficient than that of d-lactate. Despite widespread belief to the contrary, the metabolic utilization of d-lactate is quite efficient in normal men.

Bartter's syndrome is generally attributed to a primary defect in salt reabsorption either in the ascending limb of Henle's loop or in the proximal tubule. 2 siblings presented here have all the clinical and biochemical features of Bartter's syndrome but seem to have defective salt reabsorption in the distal convoluted tubule. A surreptitious use of diuretics was ruled out. Free water clearance was reduced in both patients and also was low after the addition of furosemide when compared with controls. Urine osmolalities following overnight dehydration were 883 and 1,000 mosm/l. The reduced maximal free water clearance argues against a proximal defect, and the normal urine concentration against a Henle's loop defect. Low free water clearance after furosemide suggests a defect in the distal convoluted tubule.

WE have recently studied a patient who had short-bowel syndrome that presented with peculiar neurologic manifestations and severe metabolic acidosis. The anion gap was increased, but the identity of the abnormal anion was not readily apparent. By several chemical technics the agent responsible for metabolic acidosis was found to be D-lactic acid — a cause of metabolic acidosis familiar to veterinarians but not to physicians. Case History The patient, a 30-year-old man, was in good health until July, 1975, when a superior mesenteric-vein thrombosis of unknown cause resulted in gangrene of most of the small intestine. After emergency jejunoileostomy with . . .

The proper approach to diagnosis and management in patients with a first episode of a calcium-containing kidney stone is controversial, and we have reviewed the literature in a search for objective information. Six large retrospective studies show the "natural cumulative recurrence rate of renal stones" to be 14% at 1 year, 35% at 5 years, and 52% at 10 years. Randomized studies of the use of either thiazides or allopurinol suggest a modest beneficial effect of about 35% over placebo. Considering that the risk of this specific therapy is about 5%, the morbidity associated with renal stones is limited, and relatively less invasive procedures can often replace nephrolithotomy, we conclude that use of specific drug therapy, namely thiazides or allopurinol, is not warranted in patients with a first kidney stone and, therefore, that extensive metabolic evaluation is unnecessary.

The anion gap can be readily calculated from routine laboratory data, and although it has its widest application in the diagnosis of various forms of metabolic acidosis,1 , 2 it may sometimes provi...