Evidence for disordered acid-base handling in calcium stone-forming patients.

In stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of stones. Calcium phosphate (CaP) SFs have higher urine pH than calcium oxalate (CaOx) SFs. Normal women have higher urine pH than men on fixed diets, accompanied by greater absorption of food alkali. Female CaP and male CaOx SFs have similar urine pH as same sex normal individuals, but male CaP and female CaOx SFs may have abnormal acid-base handling. We studied 25 normal individuals (13 men and 12 women), 17 CaOx SFs (11 men and 6 women), and 15 CaP SFs (8 men and 7 women) on fixed diets. Urine and blood samples were collected under fasting and fed conditions. Female CaOx SFs had lower urine pH and lower alkali absorption, fed, compared with normal women; their urine NH4 was higher and urine citrate excretion lower than in normal women, consistent with their higher net acid excretion. Male CaOx SFs had higher urine citrate excretion and higher serum ultrafilterable citrate levels than normal men. Both male and female CaP SFs had higher urine pH fasting than same sex normal individuals, but only men were higher in the fed period, and there were no differences from normal in gut alkali absorption. CaP SFs of both sexes had higher urine NH4 and lower urine citrate than same sex normal individuals. The lower urine pH of female CaOx SFs seems related to decreased gut alkali absorption, while the higher pH of CaP SFs, accompanied by higher urine NH4 and lower urine citrate, suggests a proximal tubule disorder.

The role of the clinical laboratory in diagnosing acid-base disorders.

Acid-base homeostasis is fundamental for life. The body is exceptionally sensitive to changes in pH, and as a result, potent mechanisms exist to regulate the body's acid-base balance to maintain it in a very narrow range. Accurate and timely interpretation of an acid-base disorder can be lifesaving but establishing a correct diagnosis may be challenging. The underlying cause of the acid-base disorder is generally responsible for a patient's signs and symptoms, but laboratory results and their integration into the clinical picture is crucial. Important acid-base parameters are often available within minutes in the acute hospital care setting, and with basic knowledge it should be easy to establish the diagnosis with a stepwise approach. Unfortunately, many caveats exist, beginning in the pre-analytical phase. In the post-analytical phase, studies on the arterial reference pH are scarce and therefore many different reference values are used in the literature without any solid evidence. The prediction models that are currently used to assess the acid-base status are approximations that are mostly based on older studies with several limitations. The two most commonly used methods are the physiological method and the base excess method, both easy to use. The secondary response equations in the base excess method are the most convenient. Evaluation of acid-base disorders should always include the assessment of electrolytes and the anion gap. A major limitation of the current acid-base laboratory tests available is the lack of rapid point-of-care laboratory tests to diagnose intoxications with toxic alcohols. These intoxications can be fatal if not recognized and treated within minutes to hours. The surrogate use of the osmolal gap is often an inadequate substitute in this respect. This article reviews the role of the clinical laboratory to evaluate acid-base disorders.

Epidemiology of Acid-Base Derangements in CKD.

Acid-base disorders are in patients with chronic kidney disease, with chronic metabolic acidosis receiving the most attention clinically in terms of diagnosis and treatment. A number of observational studies have reported on the prevalence of acid-base disorders in this patient population and their relationship with outcomes, mostly focusing on chronic metabolic acidosis. The majority have used serum bicarbonate alone to define acid-base status due to the lack of widely available data on other acid-base disorders. This review discusses the time course of acid-base alterations in CKD patients, their prevalence, and associations with CKD progression and mortality.

Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model).

BACKGROUND: The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome. METHODS: Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (ATOT), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model. RESULTS: According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO2, metabolic alkalosis based on decreased ATOT, and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta ATOT [(14.09 - measured ATOT) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956). CONCLUSIONS: Patients with nephrotic syndrome had primary respiratory alkalosis, decreased ATOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

Effects of potassium chloride and potassium bicarbonate in the diet on urinary pH and mineral excretion of adult cats.

Low dietary K levels have been associated with increasing renal Ca excretion in humans, indicating a higher risk of calcium oxalate (CaOx) urolith formation. Therefore, the present study aimed to investigate whether dietary K also affects the urine composition of cats. A total of eight adult cats were fed diets containing 0·31 % native K and 0·50, 0·75 and 1·00 % K from KCl or KHCO3 and were evaluated for the effects of dietary K. High dietary K levels were found to elevate urinary K concentrations (P<0·001). Renal Ca excretion was higher in cats fed the KCl diets than in those fed the KHCO3 diets (P=0·026), while urinary oxalate concentrations were generally lower in cats fed the KCl diets and only dependent on dietary K levels in cats fed the KHCO3 diets (P<0·05). Fasting urine pH increased with higher dietary K levels (P=0·022), reaching values of 6·38 (1·00 % KCl) and 7·65 (1·00 % KHCO3). K retention was markedly negative after feeding the cats with the basal diet (-197 mg/d) and the 0·50 % KCl diet (-131 mg/d), while the cats tended to maintain their balance on being fed the highest-KCl diet (-23·3 mg/d). In contrast, K from KHCO3 was more efficiently retained (P=0·018), with K retention being between -82·5 and 52·5 mg/d. In conclusion, the dietary inclusion of KHCO3 instead of KCl as K source could be beneficial for the prevention of CaOx urolith formation in cats, since there is an association between a lower renal Ca excretion and a generally higher urine pH. The utilisation of K is distinctly influenced by the K salt, which may be especially practically relevant when using diets with low K levels.

Impact of the diet on net endogenous acid production and acid-base balance.

Net acid production, which is composed of volatile acids (15,000 mEq/day) and metabolic acids (70-100 mEq/day) is relatively small compared to whole-body H⁺ turnover (150,000 mEq/day). Metabolic acids are ingested from the diet or produced as intermediary or end products of endogenous metabolism. The three commonly reported sources of net acid production are the metabolism of sulphur amino acids, the metabolism or ingestion of organic acids, and the metabolism of phosphate esters or dietary phosphoproteins. Net base production occurs mainly as a result of absorption of organic anions from the diet. To maintain acid-base balance, ingested and endogenously produced acids are neutralized within the body by buffer systems or eliminated from the body through the respiratory (excretion of volatile acid in the form of CO2) and urinary (excretion of fixed acids and remaining H⁺) pathways. Because of the many reactions involved in the acid-base balance, the direct determination of acid production is complex and is usually estimated through direct or indirect measurements of acid excretion. However, indirect approaches, which assess the acid-forming potential of the ingested diet based on its composition, do not take all the acid-producing reactions into account. Direct measurements therefore seem more reliable. Nevertheless, acid excretion does not truly provide information on the way acidity is dealt with in the plasma and this measurement should be interpreted with caution when assessing acid-base imbalance.

Distal renal tubular acidosis in mice lacking the AE1 (band3) Cl-/HCO3- exchanger (slc4a1).

Mutations in the human gene that encodes the AE1 Cl(-)/HCO(3)(-) exchanger (SLC4A1) cause autosomal recessive and dominant forms of distal renal tubular acidosis (dRTA). A mouse model that lacks AE1/slc4a1 (slc4a1-/-) exhibited dRTA characterized by spontaneous hyperchloremic metabolic acidosis with low net acid excretion and, inappropriately, alkaline urine without bicarbonaturia. Basolateral Cl(-)/HCO(3)(-) exchange activity in acid-secretory intercalated cells of isolated superfused slc4a1-/- medullary collecting duct was reduced, but alternate bicarbonate transport pathways were upregulated. Homozygous mice had nephrocalcinosis associated with hypercalciuria, hyperphosphaturia, and hypocitraturia. A severe urinary concentration defect in slc4a1-/- mice was accompanied by dysregulated expression and localization of the aquaporin-2 water channel. Mice that were heterozygous for the AE1-deficient allele had no apparent defect. Thus, the slc4a1-/- mouse is the first genetic model of complete dRTA and demonstrates that the AE1/slc4a1 Cl(-)/HCO(3)(-) exchanger is required for maintenance of normal acid-base homeostasis by distal renal regeneration of bicarbonate in the mouse as well as in humans.

Strong ion difference in urine: new perspectives in acid-base assessment.

The plasmatic strong ion difference (SID) is the difference between positively and negatively charged strong ions. At pH 7.4, temperature 37 degrees C and partial carbon dioxide tension 40 mmHg, the ideal value of SID is 42 mEq/l. The buffer base is the sum of negatively charged weak acids ([HCO3(-)], [A-], [H2PO4(-)]) and its normal value is 42 mEq/l. According to the law of electroneutrality, the amount of positive and negative charges must be equal, and therefore the SID value is equal to the buffer base value. The easiest assessment of metabolic acidosis/alkalosis relies on the base excess calculation: buffer base(actual) - buffer base(ideal) = SID(actual) - SID(ideal). The SID approach allows one to appreciate the relationship between acid-base and electrolyte equilibrium from a unique perspective, and here we describe a comprehensive model of this equilibrium. The extracellular volume is characterized by a given SID, which is a function of baseline conditions, endogenous and exogenous input (endogenous production and infusion), and urinary output. Of note, volume modifications vary the concentration of charges in the solution. An expansion of extracellular volume leads to acidosis (SID decreases), whereas a contraction of extracellular volume leads to alkalosis (SID increases). A thorough understanding of acid-base equilibrium mandates recognition of the importance of urinary SID.

Urine acid-base compensation at simulated moderate altitude.

Acute exposure to high altitude elicits respiratory alkalosis, and this is partially corrected by renal compensation. To determine the time course and magnitude of renal compensation during short-term moderate altitude exposure, we measured urine gas tensions and acid-base status in 48 healthy men and women at four levels of simulated altitude exposures. Each subject was exposed in pseudorandom order to simulated altitudes of 1780, 2085, 2455, and 2800 m in a decompression chamber for 24 h, separated by 1 week at sea level. Fresh urine was collected anaerobically at sea level and after 6 and 24 h of each altitude exposure. Urine pH increased significantly (p < 0.01) after 6 h at all altitudes and returned to baseline values by 24 h at the lowest altitudes. In contrast, urine pH remained elevated at the highest altitudes. The mean value of urine HCO at sea level was 1.67 +/- 0.25 mmol/L, increased significantly after 6 h at all altitudes, and then returned to near baseline after 24 h at three lower altitudes (1780, 2085, and 2455 m). However, it remained elevated at 2800 m. PCO2 in urine was significantly increased after 6 h and returned to baseline after 24 h at all altitudes. These results suggest that (1) short-term low to moderate altitude exposure results in a marked HCO diuresis, which may be caused by inhibition of the secretion of renal tubular H+, and (2) renal HCO compensation was completed by 24 h at low to moderate altitude, but still incomplete at higher altitude.

[Metabolic acidosis in children: the usefulness of 'anion gap']. / Metabole acidose bij kinderen: het nut van de 'anion gap'.

Metabolic acidosis occurs frequently in small children. The most common causes are hypoxia, sepsis, gastroenteritis and hypovolaemia. Calculation of the anion gap is useful in establishing the cause. An increased anion gap represents unmeasured anions, e.g. lactate in lactic acidosis. Metabolic acidosis was diagnosed in two boys aged one year and six weeks respectively. The first patient had a normal, the second an increased anion gap in blood. By determining the pH and the anion gap in urine it is possible to distinguish between a proximal and a distal tubular disease. The first patient had distal renal tubular acidosis; he recovered after correction of the acidosis. The second patient had a defect in the mitochondrial respiratory chain; he died at the age of seven months.

The primary hereditary form of distal renal tubular acidosis: clinical and genetic studies in 60-member kindred.

A distal (type 1) renal tubular acidosis (RTA-1) has been studied in 60 of 69 living members of a large family "HK" and two unrelated small families. The "HK" family, including 28 RTA-1 subjects, presents the first large family with only primary RTA-1 reported to date. The genetic situation in this family confirms the autosomal dominant transmission of the hereditary primary RTA-1 suggested previously on the basis of a few small families. Our data show that, in contrast to the secondary hereditary form, RTA-1 in its primary hereditary form is always complete and often tolerated (asymptomatic). It occurs in non-hypercalciuric families with no clinical variants observed in family members without RTA-1. In our series some clinical abnormalities commonly associated with RTA-1, such as nephrocalcinosis and growth retardation, appeared only in three cases among offspring when both parents were affected. The appearance of such abnormalities, taken as consequences of chronic acidosis in RTA-1, could be favored by the genetic background and/or the homozygosity for the RTA-1 gene. Linkage studies between RTA-1 and 10 genetic markers have been carried out. Results show that only ABO, MNS, GM and RH loci are informative for linkage analysis and none of these loci can be suggested as linked to RTA-1 locus.

Acid-base and electrolyte abnormalities in alcoholic patients.

This study was undertaken to analyze the acid-base and electrolyte abnormalities and the pathogenetic mechanisms involved in alcoholic patients admitted to our department for causes related to alcohol abuse. We studied 79 alcoholic patients aged 31-78 years. None had any other disease or was receiving drugs influencing acid-base balance and electrolyte parameters. On their admission and before any therapeutic intervention laboratory investigation of the acid-base status and electrolyte parameters in both sera and urine was carried out. Thirty-two patients (40.5%) had acid-base disturbances. Ten patients (12.6%) had pure respiratory alkalosis, 2 patients (2.5%) pure metabolic alkalosis, while 20 patients (25.3%) had the so-called syndrome of alcoholic ketoacidosis. Forty-one patients (52%) had electrolyte abnormalities. Eighteen patients (22.8%) had hyponatremia. However, 5 patients had pseudohyponatremia due to alcohol-induced hypertriglyceridemia. Two patients (2.5%) with increased insensible losses had hypernatremia. Hypokalemia was found in 10 patients (12.6%), hypomagnesemia in 25 patients (31.6%), hypophosphatemia in 23 patients (29.1%), hyperphosphatemia in 2 patients (2.5%), and hypocalcemia in 17 patients (21.5%). However, only 7 patients had true hypocalcemia. In conclusion, alcoholic patients develop a series of acid-base and electrolyte disturbances owing to various pathogenetic mechanisms.

[Corynebacteria D2 and encrusted cystitis with alkaline urine]. / Corynébactéries D2 et cystite incrustée à urines alcalines.

In the light of an informative clinical case report, the authors emphasise the pathogenic role of Corynebacteria D2 in urinary tract disease. This microorganism can be easily detected by bacteriologists by the use of special media and such infection is suggested clinically by urinary tract infection with "sterile", strongly alkaline urine. The clinical features of incrusted cystitis with alkaline urine may be accompanied by serious upper urinary tract complications with renal failure, recurrent haematuria with anaemia, decreased bladder capacity and incontinence. Corynebacteria D2, an opportunistic pathogenic bacteria, responsible for nosocomial infection, is resistant to the majority of antibiotics. The authors complete their case report with a review of the literature.

[Disorders of acid-base equilibrium in neonatal physiologic jaundice]. / Anomalie dell'equilibrio acido-base nell'ittero fisiologico neonatale.

38 healthy term jaundiced infants were tested. On 3rd day of life we obtained a blood sample from a peripheric vein to determine red blood cells and reticulocytes count, serum albumin, total, conjugated and unconjugate bilirubin. On 3rd, 4th, 5th, 6th day of life 4 standard heparinized microtubes were filled after lancing the heel: 2 microtubes to estimate the mean value of total bilirubin, 2 for the mean value of pH. The urine pH was evaluated every morning. The results of total bilirubin (T.B.), pH, pCO2 and Base Deficit were analyzed using T-test. All tested infants were free-bilirubin jaundiced. Infants treated with phototherapy had a T.B. ranging from 15.2 mg/dl on 3rd day of life to 10.5 mg/dl on 6th, while in controlled infants T.B. never exceeded 10 mg/dl. In treated infants the pH was higher than in controlled ones: p was less than 0.001 on 4th day, less than 0.005 on 5th day and less than 0.001 on 6th day. In both groups the urine pH ranged from 5 to 6.5 every day. The marked increase in respiratory rate during phototherapy is a well known side effect. But a significant decrease in pCO2 was present before starting phototherapy. A mixed disturbance of acid-base balance could be suspected: an already existing mild metabolic acidosis in phototherapy group with respiratory alkalosis due to anion gap variety, with unknown determining causes. We relate the initial metabolic acidosis to the depressed oxidative phosphorylation (with lactic acidosis) in the neonatal liver.(ABSTRACT TRUNCATED AT 250 WORDS)

The nature of the renal response to chronic disorders of acid-base equilibrium.

The rate of acid excretion by the kidney appears to be determined by factors regulating the site and the rate of sodium reabsorption, rather than by a homeostatic mechanism that responds to systemic pH. This hypothesis, although unconventional, is supported by much experimental evidence, and it accounts for a wide variety of clinical and physiologic findings that heretofore have been difficult or impossible to explain.