chronic diet acid and mineral metabolism in...
TRANSCRIPT
Minerals and Trace Elements
The Effect of Chronic Dietary Acidification UsingAmmonium Chloride on Acid-Base and MineralMetabolism in the Adult Cat1
SHELLEY V. CHING,2 MARTIN J. FETTMAN,3 DWAYNE W. HAMAR, LARRY A. NAGODE*
ANDKATHARINE R. SMITHDepartment of Pathology, Colorado State university, Ft. Collins, CO 80523 and ""Department of
Veterinary Pathobiology, The Ohio State University, Columbus, OH 43210
ABSTRACT Adult cats with normal renal function werefed a nutritionally balanced, vitamin A-repIete, experimental dry diet with or without ammonium chloride (NH4C1)for6 mo to study the effects of chronic dietary acidificationon acid-base parameters and the metabolism of selectedminerals. Dietary balance studies were performed monthly.Blood and urine samples were collected monthly to evaluate acid-base parameters, plasma parathyroid hormone(PTH) and 1,25-dihydroxycholecalciferol levels. Ammonium chloride-treated cats had significantly lower bloodand urinary pH, and lower blood bicarbonate concentrations. Treated cats also had higher blood ionized calciumconcentrations, hypercalciuria and lower intestinal calciumabsorption relative to baseline (prior to feeding the experimental diet) and to control cats. This resulted in the development of lower calcium balance in the first severalmonths. PTH levels were unaffected by dietary acidification;however, 1,25-dihydroxycholecalciferol levels were significantly decreased in treated cats. Treated cats had negativepotassium balance during 5 mo of dietary acidification.Magnesium, sodium, and phosphorus balances were lower,but positive, in treated cats compared to control cats. Catsconsuming the NH4CI-supplemented diet had increasedchloride balance. Thus, chronic dietary acidification with1.5% NH4C1produced chronic metabolic acidosis and lower,or negative, calcium and potassium balance. J. Nutr. 119:902-915, 1989.
INDEXING KEY WORDS:
•cats •1,25-dihydroxycholecalciferol•chronic metabolic acidosis •calcium andpotassium balance •parathyroid hormone
Chronic ingestion of ammonium chloride (NH4C1)produces metabolic acidosis and alterations in calciummetabolism in humans, rats, dogs, sheep and chickens(1-9). These alterations include increased blood ionized calcium concentrations, increased urinary excretion of calcium, normal to decreased intestinal absorp
tion of calcium and increased mobilization of calciumfrom bone (1-9). These effects result in a negative netcalcium balance. During metabolic acidosis, the responses of kidney, intestine and bone may be mediatedby changes in 1,25-dihydroxycholecalciferol and para
thyroid hormone (PTH). Some data indicate that theeffects of calcium metabolism are independent of PTHand dietary levels of calcium (8, 10). There is a paucityof information regarding the metabolism of other minerals in metabolic acidosis, but phosphorus, magnesium, potassium, chloride and sodium metabolism maybe variably affected. Studies have demonstrated thatchronic metabolic acidosis (CMA) may lead paradoxically to potassium depletion with the development ofhypokalemia (11, 12). In acidosis, metabolism of magnesium, the fourth most abundant cation in the body,is similar to that of calcium. There is a redistributionbetween intracellular and extracellular compartments,increased urinary magnesium excretion and increasedmobilization of magnesium from readily exchangeableskeletal apatite crystals (13, 14). In addition to changesin the metabolism of each of these minerals, combinedalterations in calcium, potassium and magnesium metabolism can be seen in metabolic acidosis, due to theirphysiological interrelationships (13). Renal handling ofsodium and chloride also may be affected by metabolicacidosis secondary to decreased filtered bicarbonate andreduced bicarbonate reabsorption in the renal proximaltubule (11).
Ammonium chloride is commonly used in the treatment and prevention of feline urologie syndrome. Feline urologie syndrome is a multifactorial disorder of
'Supported by the Ralston Purina Company, Robert H. Winn Foun
dation, and the Morris Animal Foundation.
2Present address: Dept. of Pathology (R-46), University of Miami
School of Medicine, Miami, FL 33101.3To whom reprint requests should be addressed.
0022-3166/89 $3.00 ©1989 American Institute of Nutrition. Received 22 August 1988. Accepted 14 February 1989.
902
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the feline lower urinary tract characterized by difficultyor increased frequency in urination, straining to urinate, blood and/or crystals in the urine, cystitis, ure-thritis and/or urethral obstruction (15). The rate of occurrence of struvite (magnesium-ammonium-phosphate)crystal formation and feline urologie syndrome increases when the urinary pH is greater than 6.4 (15).The concentration and salt form of minerals in theurine, in particular magnesium, also may be very important in enhancing the formation of struvite crystalsand producing an alkaline urine (15).Ammonium chloride has been shown to be an efficacious urinary acidifier in the management of this disorder and in mostcases must be given for long periods of time (16, 17).
Although the effects of dietary acidification have beenstudied in rats, dogs and humans, the potentially detrimental effects on systemic metabolism by chronicdietary acidification using NH4Cl in the cat have notbeen evaluated. The purpose of this study was to feed1.5% NH4C1 for 6 mo to adult cats with normal renalfunction to induce chronic metabolic acidosis and toevaluate long-term effects of this dietary supplementation on acid-base balance and the metabolism of selected minerals.
MATERIALS AND METHODS
Animals and diets. Twenty-two adult, healthy, specific-pathogen-free domestic cats were obtained for thisstudy from E. A. Hoover (Department of Pathology,Colorado State University, Ft. Collins, CO). Cats rangedin age from 1 to 6.5 years (mean = 2.2 ±1.4). Therewere 12 castrated male cats and 10 female cats, two ofwhich were spayed. All cats were individually housedin stainless steel cages in a light (12-h cycle) and temperature-controlled (22.2°C)room, and provided water
and food ad libitum. Each cat received daily exercisewithin the room for approximately l h during the cage-cleaning period.
All cats were acclimated to their environment anddiet for a minimum of 2 mo before the beginning ofthe experiment. During the first month, the cats werefed a commercial nonpurified diet (Purina Cat Chow,Ralston-Purina, St. Louis, MO) ad libitum. At the endof the first month of acclimation, each cat was evaluated for normal renal function by measuring glomerularfiltration rate and effective renal plasma flow (18).During the second month, an experimental, nutritionallybalanced, neutral, dry basal diet (mixed, extruded andpackaged by Ralston-Purina per our specification; Table1) was fed ad libitum. Table 2 gives the analyzed composition of the experimental diet. The cats were pairedfor age and sex and divided into two groups of 11 catseach. The controls continued to consume the experimental basal diet. The experimental group consumedthe basal diet plus 1.5% ammonium chloride. Eachgroups was fed its respective diet ad libitum for 6 mo.
Procedure for metabolic balance studies. At the end
TABLE1
Ingredient composition of the basal experimenta/ diet
Ingredient Amount
Ground and whole yellow corn1
Poultry mealSoybean mealWheatBone and meat mealDicalcium phosphateFish mealNaCl (iodized)Vitamin premix2Brewer's yeastTrace mineral mix2
Choline chlorideSpray-on fat digest
of dry matter42.9426.0010.009.003.001.001.000.700.670.400.200.095.00
'Cornmeal (1.5%) was replaced by 1.5% ammonium chloride in
the acidified experimental diet.2A standard feline mix, supplied by Ralston-Purina, St. Louis, MO.
Composition is a trade secret.
of the second month of acclimation, designated mo 0,baseline dietary balance studies were conducted on eachcat. Balance studies were performed every 4 wk thereafter for 6 mo. Each cat was individually placed in ametabolism cage to measure food intake and urine andfecal output. The cats were weighed at the beginningof each study. Food and deionized water were given adlibitum during the collection period. All collection periods continued for four consecutive days (96h). Duringthis time, daily food intake and total food consumptionwere measured, and the average daily food consumption was calculated. Urine samples were collected separately from feces into closed containers and calculation of total volume and average daily urine excretionwere determined from pooled samples. All feces werecollected and pooled for each cat, oven-dried at 100°C
for 3 d, weighed, and total fecal excretion and averagedaily fecal excretion on a dry weight basis were calculated.
TABLE 2
Chemical composition of the basal and acidified experimentaldiets
IngredientCrude
proteinAshFatCalciumPhosphorusPotassiumSodiumMagnesiumChlorideBasal
dietÕ29.78.008.621.761.240.570.470.150.51Acidifieddieto
of dry matter30.6'8.007.761.681.220.550.510.151.61
'Corrected for the amount of nitrogen contributed by 1.5% NH4C1.
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Urine and blood collection and analysis. Urine samples collected during the balance studies were dividedinto two aliquots. One contained unacidified urine, andthe other was acidified to below pH 2.0 by diluting nineparts urine with one part 6 N HNO3. Samples werestored frozen at 4°Cfor later analysis of Ca, P, Na, K,
Mg, Cl and creatinine. Fractional excretion (% )for eachmineral was calculated as: [(concentration of mineralin urine/urine creatinine concentration) x (plasma creatinine concentration/concentration of mineral inplasma)) x 100. For each mineral, amount digestible(%) was calculated as: [(intake - fecal)/intake] x 100.
Urine was also collected anaerobically by cystocentesisduring the week following the dietary balance studyand urinary pH was measured immediately (CorningDigital 112 Research pH meter, Corning Medical, Med-
field, MA).During each 4-d dietary balance collection period,
venous blood samples (10 ml) were collected between0900 and 1000 h from unanesthetized cats into lithium-
heparinized syringes (Sarstedt, Princeton, Nf ).Blood pHand ionized calcium concentration were determinedimmediately using an ion-selective electrode calciumanalyzer (Radiometer ICa-1 analyzer, RadiometerAmerica, Westlake, OH) and blood gas analyses (Corning 165/2 blood gas analyzer) were determined within1 h. Plasma was frozen and stored for later analysis ofNa, K, Ca, P, Mg, Cl, creatinine, 1,25-dihydroxychole-
calciferol and parathyroid hormone concentrations.Feed and fecal sample analyses. Percent moisture,
dry matter, and ash (both wet wt and dry wt) weredetermined for feed and fecal samples. All samples wereashed overnight in a muffle furnace at 600°C.Ashed
samples were dissolved in 5 ml of 6 N HNO3, transferred to a 50- or 100-ml volumetric flask (feed and fecalsamples, respectively) and brought to volume withdeionized, distilled water for later analysis of Ca, P andMg.
Calcium. Calcium concentration in plasma, urine,feces and feed was determined by atomic absorptionspectroscopy (Varian AA-1275 Atomic Absorption
Spectrophotometer, Varian, Palo Alto, CA). Plasma andashed solutions of fecal and feed samples were dilutedwith 0.5% lanthanum and the absorbance was determined using an air-acetylene flame. Urinary calciumwas measured using acidified urine samples diluted with0.2% KC1, and the absorbance was determined using anitrous oxide-acetylene flame.
Phosphorus. All samples were analyzed for phosphorus by spectrophotometry (Gilford Model 250 spec-trophotometer, Gilford Instrument Laboratories, Ober-
lin, OH) using a molybdate reagent (Phosphorus reagent,Sigma Chemical, St. Louis, MO) and determined at 340nm with the visible light source.
Magnesium. Plasma, acidified urine, fecal and feedmagnesium were determined by atomic absorptionspectroscopy. Samples were diluted with 0.5% lanthanum and analyzed with an air-acetylene flame.
Sodium and potassium. Sodium and potassium concentrations in plasma and unacidified urine were determined by an ion-selective electrode analyzer (Radiometer KNa-1 analyzer, Radiometer America, Westlake,
OH). Fecal and feed sodium and potassium concentrations were determined by atomic absorption spectroscopy. Approximately 0.2 g of feed (wet wt) or feces (drywt) were extracted with 9.99 ml of 0.05 N HNO3. Sodium was analyzed using 0.2% KC1 as sample diluent.Potassium was analyzed with 0.1% CsCl as samplediluent.
Chloride. Chloride determination of all samples wasperformed using a digital chloridometer (Haake BuchlerInstruments, Saddle Brook, NJ). Feed and fecal chlorideconcentrations were determined on the supernatant obtained from an extract of ground feed (wet wt) or fecalsample (dry wt) by mixing 0.5 g with 5 ml 0.05 N HNO3.
Creatinine. Plasma and urinary creatinine were analyzed by the Jaffe alkaline picrate rate method (Creatinine analyzer 2, Beckman Instrument, Brea, CA).
Endocrine analyses. Plasma concentration of the biologically active, amino terminal-specific parathyroidhormone was assayed as described by Potts, Segre andEndres (19) and by Endres et al. (20). Plasma concentration of 1,25-dihydroxycholecalciferol was assayed bythe method of Nagode and Steinmeyer (21), incorporating micromodifications developed by Horst et al. (22).
Statistical analyses. The Student's unpaired i-test was
used for each parameter to compare differences in themeans between the control group and the NH4Cl-treatedgroup at each month during the study. A two-way anal
ysis of variance with repeated measures was performedwithin the two groups on all parameters measured eachmonth, in order to evaluate differences which may haveoccurred over time. Fisher's least significant difference
test was used to rank the means and identify thosemonths with means that were significantly differentfrom the mean of the baseline control month. The analysis of variance took into consideration the variabilitydue to cat, treatment and time. Results were consideredstatistically significant at P < 0.05, and were considered as trends or tendencies which may be significantat 0.1 > P > 0.05. Relationships between acid-baseparameters, calcium, PTH and 1,25-dihydroxycholecalciferol were determined by linear regression analyses and correlation coefficients. Data are expressed asthe mean ±standard deviation in text and tables. Thebaseline control month was designated mo 0 and mo1-6 are treatment months.
RESULTS
There were no significant differences in body weightbetween NH4Cl-treated and control cats during thestudy. Both groups, when averaged, significantly (P <0.05) gained weight over the experimental period: treatedcats, 3.60 ±0.98 vs. 3.27 ±0.60 kg; controls, 3.67 ±1.05 vs. 3.44 ±0.89 kg for mo 6 and mo 0, respectively.
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The mean percentage change in body weight betweenmo 0 and mo 6 was 4.07 ±11.57% in the treated catsand 6.26 ±11.78% in the control cats, with no significant differences between the two groups.
Average daily food consumption was not significantly different between the groups during the study,but with time both groups significantly (P < 0.05) decreased their food consumption (g/kg body wt): treatedcats, 15.88 ±3.17 vs. 21.18 ±3.79; controls, 18.16 ±3.03 vs. 21.64 ±4.79 for mo 6 and mo 0, respectively.
Acid-base parameters are summarized in Figure 1 andindicate that the cats fed NH4C1 for 6 mo developedmetabolic acidosis and remained significantly acidoticthroughout the study compared to control cats. BloodpH (Fig. la) and blood bicarbonate (Fig. l£>)were significantly lower in treated cats than in control cats.Blood pCO2 and anióngaps were not different betweentreatment groups, and values remained constant withtime (data not shown). Urinary pH (Fig. le) in treatedcats was significantly lower than in control cats, andsignificantly lower in all treatment months relative tomo 0.
Calcium metabolism (Table 3) was significantly affected by long-term dietary acidification. The treatedcats had higher blood ionized calcium concentrations(Fig. 2a) than did the control cats, and higher concentrations relative to mo 0 during all months. Linearregression analyses of blood pH, blood bicarbonate concentration and actual blood ionized calcium concentration demonstrated very poor correlation. Total plasmacalcium concentrations (Fig.2b] were not significantlydifferent between or within treatment groups at anytime during the study.
Treated cats had significantly higher urinary fractional excretion of calcium (FECa,Fig. 3a) and averagedaily urinary excretion of calcium (Fig. 3fo) than didcontrol cats. The values peaked in the first severalmonths and gradually declined toward baseline. Linearregression analyses between FECaand urinary pH, bloodpH or blood HCO3 demonstrated poor correlation forpooled values (treated and control groups combined),and for the treated group by month. There was poorcorrelation between blood ionized calcium concentration and FECafor pooled values or by month. However,there was a significant positive correlation between bloodionized calcium concentration and FECain the treatedcats in mo 1, 2 and 3 (r = 0.83, 0.90 and 0.89, respectively, P < 0.05).
The average daily intake of calcium significantly declined in both groups of cats after mo 2. In the last 2mo, calcium intake was significantly lower in treatedcats compared to control cats. There were no significant differences in the average daily fecal excretion ofcalcium between treatment groups throughout the study,although both groups had decreases in fecal excretionof calcium in the last several months of the experiment.This pattern was present for all minerals measured inboth groups. Percent digestible calcium was used as an
indicator of the apparent amount of calcium absorbedfrom the ingested diet. Percent digestible calcium wassignificantly lower in treated cats in mo 4 than in con-
726
26-,
5.4
234
Time (month)
FIGURE 1 The effect of chronic dietary acidification using1.5% ammonium chloride on the acid-base parameters ofblood pH ¡A),blood bicarbonate (B) and urinary pH (C) inadult cats. Values are mean ±SEM,n = 11 cats in each groupexcept for urinary pH, where n = 6 cats in each group duringmo 0 and 1, and in all other months n = 11 cats in the treatedgroup and n - 10 cats in the control group. 'Significantdifference, P < 0.05, between groups. °Significantly different,P < 0.05, from mo 0 (baseline).
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TABLE3
Effects of chronic dietary acidification on calcium metabolism in adult cats '
0Average
daily intake of calciumAcidified 8.79 ±1.57Basal
8.98 ±1.99Averagedaily fecal excretion of
Acidified 7.77 ±1.71Basal7.51 ±2.32Digestible
calcium, %Acidified 11.0 ±17.1Basal
16.9 ±12.91,
mmol/kg body wt7.85 ±1.688.46
±1.89calcium,mmol/kg
7.83 ±2.027.43±1.99-0.9
±22.6*12.4±11.227.19
±7.69±body
wt7.20±7.54
±-0.7
±0.6±Month
31.44*1.53*1.401.318.413.0*6.56
±7.20±6.67
±6.76±-3.2
±5.6±1.68*1.51'1.741.5317.411.5»46.15
±7.50±5.85
±6.12±3.7
±17.9±1.90*1.82*1.90*1.54*14.8'14.655.62
±6.77±5.30
±6.18±6.7
±7.9±1.21
**1.16*1.61*1.11*16.512.466.26±7.53±5.79
±6.70±7.7
±11.5±1.25*'1.26*1.32*1.7111.216.3
'Values represent means ±SD,n = 11 cats per treatment group. Month 0 was the baseline month, and months 1-6 were treatment months.'Significantly different, within a parameter, from the corresponding basal diet group (P < 0.05). 'Significantly different, across a horizontalrow, from baseline (month 0| values (P < 0.05). s Differs from the corresponding basal diet group, 0.1 < P < 0.05.
1.45.
2.70.
2.20.
Time (month)
FIGURE 2 The effect of chronic dietary acidification using1.5% ammonium chloride on blood ionized calcium (A) andtotal plasma calcium (B) concentration in adult cats. Valuesare mean ±SEM,n = 11 cats in each group. *Significantdifference, P < 0.05, between groups. °Significantly different,P < 0.05, from month 0.
trol cats. Total daily calcium balance (Fig. 3c) in treatedcats was lower and negative, particularly in mo 1-3relative to mo 0, and in mo 4 compared to control cats.
Phosphorus metabolism (Table 4) was less affectedby chronic dietary acidification. No significant differences were noted in plasma phosphorus between groups,although concentrations decreased significantly in bothgroups with time. Urinary fractional excretion of phosphorus (FEp) appeared unaffected by dietary acidification, but the average daily urinary excretion of phosphorus significantly decreased with time in both groups.The average daily phosphorus intake significantly decreased in both groups of cats. There were no significantdifferences in average daily fecal excretion of phosphorus between the groups, but decreased fecal phosphorusexcretion was noted in both groups with time. In mo4, the percent digestible phosphorus was significantlylower in treated cats compared to control cats. Withinthat month, there was also a significantly lower dailyphosphorus balance in treated cats compared to controlcats.
The changes in magnesium metabolism resulting fromdietary acidification are summarized in Table 5. Therewere no significant differences in plasma magnesiumconcentrations between or within groups during theexperiment. Urinary fractional excretion of magnesium(FEMg)and average daily urinary excretion of magnesium were higher in mo 5 and 6 in treated cats than incontrol cats. Average daily intake of magnesium decreased significantly in both groups of cats after mo 2,and was significantly lower in treated than in controlcats in mo 5 and 6. No significant differences werepresent between groups in average daily fecal excretionof magnesium, although both groups had significantdecreases in fecal magnesium excretion in the last several months of the experiment relative to mo 0. Therewere no significant differences in percent digestiblemagnesium. Daily magnesium balance was lower intreated than in control cats, and significantly so duringmo 1, 4 and 6.
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Chloride metabolism (Table 6) was significantly affected by dietary supplementation with NH4C1.Plasmachloride concentration, urinary excretion of chlorideand average daily intake of chloride were significantlyhigher in treated than in control cats and relative tomo 0. There were no significant differences in average
0.3-,
0.04
S!h
O 1 2 3 4 S 6
Tim« (month)
FIGURE 3 The effect of chronic dietary acidification using1.5% ammonium chloride on urinary fractional excretion ofcalcium (%) (A), average daily urinary excretion of calcium[B] and daily calcium balance (C) in adult cats. Values aremean ±SEM,n = 11 cats in each group except in mo 0, wheren = 5 cats in the treated group and n = 10 cats in the controlgroup. *Significant difference, P < 0.05, between groups.0Significantly different, P < 0.05, from mo 0.
daily fecal excretion of chloride between treatmentgroups. The percent digestible chloride and chloridebalance (Fig.4) were significantly higher in the cats fedthe NH4Cl-supplemented diet compared to the controlgroup and relative to mo 0.
The effects on potassium metabolism are given inTable 7. There were no significant differences in plasmapotassium concentration. Urinary excretion of potassium was not significantly different between the groups.Average daily intake of potassium decreased significantly in both groups of cats after mo 2 and was significantly lower for treated cats compared to controlcats during mo 5 and 6. Fecal excretion of potassiumand percent digestible potassium were generally unaffected by dietary acidification except in mo 6 relativeto mo 0, when there was a significant increase in thepercent digestible potassium in treated cats. Potassiumbalance (Fig.5) was significantly lower and/or negativein treated compared to control cats and relative to mo0.
The effects of chronic dietary acidification on sodiummetabolism are summarized in Table 8. Plasma sodiumconcentration was not significantly different betweentreatment groups. FENawas significantly higher in treatedthan in control cats in mo 1 and 6, but was still withinthe range of normal values for cats (23). The averagedaily urinary excretion of sodium was increased in treatedcats in the first 2 mo. Average daily intake of sodiumdecreased after mo 3 in both groups of cats, but therewere no significant differences between groups. Therewere no significant differences in average daily fecalexcretion of sodium or percent digestible sodium between treatment groups. The percent digestible sodium, however, was significantly increased in the treatedgroup in all months relative to mo 0. Daily sodiumbalance was variable in the treated cats.
There were no significant differences in plasma parathyroid hormone concentration between groups (Fig.6a). Linear regression analyses revealed poor correlations between PTH and ionized calcium concentration,FECaand FEP(all of which were also poorly correlated).
Plasma 1,25-dihydroxycholecalciferol concentration(Fig.6b) was significantly lower in treated than in control cats. Within the treated group, there were also significant decreases in 1,25-dihydroxycholecalciferol, inall months of the study relative to mo 0. PTH, 1,25-dihydroxycholecalciferol, percent digestible calcium andionized calcium concentration were poorly correlated.The linear regression analysis between 1,25-dihydroxycholecalciferol and FECademonstrated a significantnegative correlation in the treated cats in mo 1 and 2(r = 0.80 and 0.85, respectively, P < 0.05).
DISCUSSION
This study examined the effects of dietary supplementation with 1.5% NH4C1for 6 mo on systemic acid-base balance and the metabolism of selected minerals
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TABLE4
Effects of chronic dietary acidification on phosphorus metabolism in adult cats'
0 12Plasma
phosphorus,mmol/1Acidified1.84 ±0.17 1.85 ±0.38 1.86 ±0.37Basal1.94 ±0.29 1.90 ±0.23 1.86 ±0.27Urinary
fractional excretion of phosphorus,%Acidified14.61 ±4.05 13.42 ±3.52 12.22 ±3.74Basal11.52 ±2.55 12.45 ±3.00 13.31 ±2.54Average
daily urinary excretion of phosphorus, mmol/kg bodywtAcidified1.09 ±0.43 1.00 ±0.10 0.92 ±0.25Basal1.03 ±0.25 1.05 ±0.32 0.96 ±0.29Average
daily intake of phosphorus, mmol/kg bodywtAcidified8.03 ±1.44 7.38 ±1.58 6.75 ±1.35'Basal8.21 ±1.82 7.73 ±1.73 7.03 ±1.40'Average
daily fecal excretion of phosphorus, mmol/kg bodywtAcidified5.89 ±1.34 5.56 ±1.65 4.93 ±0.73'Basal5.81 ±1.93 5.23 ±1.51 5.27 ±1.04Digestible
phosphorus,%Acidified26.2 ±14.8 24.3 ±16.3 26.0 ±8.2Basal30.2 ±11.5 32.6 ±9.5 24.0±11.2Daily
phosphorus balance, mmol/kg bodywtAcidified1.05 ±1.08 0.81 ±1.29 0.90 ±0.74Basal1.37 ±0.99 1.50 ±0.84 0.80 ±1.04Month
31.71
±0.271.66±0.36'12.53
±3.0414.52±3.44'0.80
±0.23'0.86±0.27'6.16
±1.58'6.58±1.38'4.50
±1.20'4.60±0.99'25.8
±14.829.5±8.80.87
±0.901.12±0.6641.70
±0.211.59±0.14'11.98
±3.0913.90±2.650.76
±0.12'0.84±0.23'5.78
±1.79'6.86±1.66'4.11
±1.44*4.10±1.05'28.5
±11.0*40.0±8.2'0.68
±0.56-1.91
±0.9251.58
±0.23'1.62±0.26'12.76
±2.4413.82±4.120.79
±0.20'0.77±0.22*5.28
±1.13*'6.19±1.06'3.86
±1.22'4.33±0.71*27.8
±14.329.2±10.30.63
±0.731.09±0.7961.58
±0.36*1.64±0.33'13.83
±5.38*14.97±3.71'0.66
±0.15"0.84±0.22'5.88
±1.17*'6.89±1.15»4.06
±1.04'4.52±1.02'31.3
±9.834.4±9.31.15
±0.651.53±0.90
'See footnote in Table 3 for further information and key to symbols.
in adult cats with normal renal function. Results support conclusions from other species (6-8) that 1.5%NH4C1 induces a sustained chronic metabolic acidosis(CMA) with accompanying alterations in calcium metabolism, resulting in the development of a significantly lower and sometimes negative calcium balancein the first 4 mo. Potassium metabolism was also significantly affected by dietary acidification, in whichlower and negative potassium balance developed. Metabolism of phosphorus, magnesium and sodium wasaffected less by chronic dietary acidification. Chloridebalance was significantly higher in the treated cats dueto the ingestion of NH4C1. The effects of CMA on minerals other than calcium have been less well studiedand the mechanisms of action are poorly understood.
The acidified diet was palatable and the cats appearedclinically normal during the experimental period. Increased average body weight in cats of both groups maybe due to continued growth in the younger cats or accumulation of body fat from insufficient exercise and/or confinement. Cats regulate their food intake well tomeet their energy need, and it is possible that withincreased confinement and less physical activity, theirenergy requirement was lowered so that food consumption was also lowered (15).
In this study, 1.5% NH4C1 produced a sustainedchronic metabolic acidosis. Both blood pH and bicarbonate concentration in the treated cats showed noevidence of adaptation by the end of the study, indicating continuing acid retention as a result of a sustained acid load. Early respiratory compensation through
a decrease in blood pCO2 may have transiently occurred, but was not seen at our later sampling times.Another continuous buffer system, such as mobilizedbone calcium (i.e., calcium carbonate and calciumphosphate), may have stabilized blood pH and bicarbonate at a reduced level in the treated cats.
The urine was effectively acidified using 1.5% NH4C1throughout the treatment period. Urinary pH was consistently below pH 6.4, which is the value recommended to prevent the formation of struvite crystalsin the feline urinary tract (15). These results are consistent with previous studies on the efficacy of NH4C1as a urinary acidifier in cats (16, 17).
Treated cats had sustained elevated blood ionizedcalcium concentrations in all months of dietary acidification. Potential sources for increased blood ionizedcalcium levels include dissociated ionized calcium fromprotein-bound and complexed forms, mobilized bonecalcium and dietary calcium. The association betweenblood pH and ionized calcium concentration is wellknown (24-26). Although blood ionized calcium concentration increased significantly in treated cats compared to the control cats, there were no differences intotal plasma calcium. Previous studies in humans, dogsand rats have reported variable total calcium levels withmost being normal to decreased (2, 4, 5, 8, 9).
Increased blood ionized calcium concentrations inthe treated cats also may be due to increased mobilization of bone calcium to serve as an additional bufferto titrate excess acid (6, 7, 9, 27, 28). Bone, with itslarge store of calcium carbonate, calcium phosphate
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TABLE5Effects oÃchronic dietary acidification on magnesium metabolism in adult cats1
0 12Plasma
magnesium,mmol/1Acidified0.97 ±0.13 0.96 ±0.10 0.97±0.12Basal0.98 ±0.08 0.98 ±0.05 1.02 ±0.10Urinary
fractional excretion of magnesium,%Acidified3.21 ±1.26* 3.98 ±1.21'* 3.59 ±1.14Basal2.31 ±0.69 2.73 ±1.02 2.83 ±1.37fAverage
daily urinary excretion of magnesium, mmol/kg bodywtAcidified0.11 ±0.07 0.16 ±0.03*' 0.14 ±0.05*Basal
0.10 ±0.05 0.12 ±0.05 0.12 ±0.07Averagedaily intake of magnesium, mmol/kg bodywtAcidified
1.26 ±0.23 1.14 ±0.24 1.04±0.21*Basal1.29 ±0.29 1.21 ±0.27 1.10 ±0.22'Average
daily fecal excretion of magnesium, mmol/kg bodywtAcidified1.05 ±0.24 0.91 ±0.23 0.84 ±0.16fBasal
1.00 ±0.33 0.87 ±0.23 0.88 ±0.14Digestiblemagnesium,%Acidified
15.9 ±18.9 19.3 ±14.5* 19.3 ±4.6Basal22.8 ±13.2 29.1 ±7.0 18.7 ±13.1Daily
magnesium balance, mmol/kg bodywtAcidified0.10 ±0.21 0.07 ±0.18' 0.06 ±0.07Basal
0.18 ±0.17 0.22 ±0.10 0.10 ±0.15Month
30.94
±0.120.98±0.073.76
±1.262.96±1.09'0.13
±0.050.11±0.050.95
±0.24'1.03±0.22'0.77
±0.20'0.80±0.17'18.6
±13.021.2±11.00.05
±0.130.12±0.1140.92
±0.090.96±0.113.47
±0.99*2.58±1.200.12
±0.040.10±0.050.89
±0.28'1.07±0.26'0.71
±0.24'0.75±0.16'20.0
±12.4*30.0±12.10.03
±.10*0.24
±0.1750.95
±0.111.02±0.073.22
±0.87-2.17
±0.970.12
±0.04-0.08
±0.040.82
±0.18"0.97±0.17'0.65
±0.21'0.77±0.13'21.1
±15.219.8±12.20.05
±0.110.12±0.1260.97
±0.111.00±0.103.75
±1.21*2.59
±0.850.11
±0.02-0.09
±0.030.91
±0.18"1.08±0.18'0.68
±0.18'0.78±0.19'25.4
±11.828.4±8.90.11
±0.10'0.21
±0.09
'See footnote to Table 3 for further information and key to symbols.
and other alkaline salts, as well as large surface availability of sodium and potassium as readily exchangeable ions for H +, has been determined to be a sourceof extrarenai buffering (6, 8, 9, 28-31). It is unclearwhether bone mineral is mobilized by direct dissolution due to the acidic environment or to increased cell-mediated bone résorption(5, 32-34). Quantitative his-
tomorphometric analysis of trabecular bone remodeling in iliac crest biopsies revealed no significant differences in total trabecular bone volume or cellularremodeling activity as a result of chronic dietary acidification in these cats (data not shown). Bone mineralcontent assessed by computed tomography was not decreased in the treated cats. It is possible that dissolutionof surface available calcium was an additional sourceof increased ionized calcium in the treated cats (Ching,S. V., et al., unpublished data).
The blood concentration and effects of PTH on boneduring CMA may be important in skeletal responses(35, 36). Increased sensitivity of bone to PTH may occur, resulting in increased bone résorption.Studies havedemonstrated that stimulated osteoclastic osteolysis ispresent in animals during chronic NH4C1 ingestion inthe absence of PTH, which suggests that bone calciumrelease from increased bone résorptionis independentof the action of PTH and may be due to acidity itself(5, 34, 37, 38). In our study, plasma PTH concentrationwas not significantly different between groups, but thisdoes not exclude the possibility that the end organ response to PTH was altered. In the treated cats, the bloodionized calcium concentration was significantly increased and it would be expected that PTH levels should
decrease. This did not occur, and it is unknown as towhat ionized calcium concentration in cats should elicita detectable decrease in PTH secretion. Another potential explanation may be that decreased 1,25-dihy-
droxycholecalciferol levels in the treated cats loweredthe responsiveness of the parathyroid gland to the sup-
pressive effect of increased blood ionized calcium concentrations (39).
Cholecalciferol is a potent bone resorbing hormonewhich acts synergistically with PTH to regulate bodycalcium (40). Because plasma 1,25-dihydroxycholecal-
ciferol concentration was significantly reduced in thetreated cats, it is an unlikely contributor to bone mineral mobilization. It is likely that lower 1,25-dihydroxy-cholecalciferol concentration in the treated cats contributed to a lower percent digestible calcium, whichwas significantly lower in treated than in control catsin mo 4 and decreased relative to mo 0. This suggeststhat the increase in blood ionized calcium concentrations in the treated cats was not due to increased dietaryintake or intestinal absorption of calcium.
In the treated cats, significant hypercalciuria was evidence of altered renal handling of calcium during CMA.Both fractional excretion of calcium (FECa)and averagedaily urinary excretion of calcium were initially increased; however, with time, urinary calcium excretiondeclined towards baseline values. Hypercalciuria in thetreated cats was similar to other results, which haveshown that CMA produces increased urinary calciumexcretion (7, 10, 41, 42). Proposed mechanisms for CMA-induced hypercalciuria (10,43,44) include: Õ)decreasedrenal tubular reabsorption of calcium by an unknown
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910 CHING ET AL.
TABLE6Effects of chronic dietary acidification on chloride metabolism in adult cats '
0 12Plasma
chloride,mmo¡/¡Acidified109.27 ±4.82 112.00 ±3.52«* 111.18 ±5.98Basal109.09 ±3.53 109.09 ±3.67 108.00 ±4.71Urinary
fractional excretion of chloride, %Acidified 0.63 ±0.17* 1.68 ±0.40" 1.47 ±0.41*'Basal
0.46 ±0.09 0.48 ±0.09 0.52 ±0.11Averagedaily urinary excretion of chloride, mmol/kg body wt
Acidified 2.49 ±0.69 7.84 ±1.23*f 6.69 ±1.67"Basal
2.39 ±0.67 2.38 ±0.76 2.19 ±0.68Averagedaily intake of chloride, mmol/kg body wt
Acidified 2.86 ±0.51 8.46 ±1.81*' 7.74 ±1.55"Basal2.92 ±0.65 2.75 ±0.62 2.50 ±0.50'Average
daily fecal excretion of chloride, mmol/kg body wtAcidified 0.33 ±0.17 0.36 ±0.20 0.31 ±0.16Basal
0.35 ±0.19 0.31 ±0.17 0.27±0.11'Digestiblechloride, %
Acidified 88.7 ±5.3 95.9 ±1.8" 96.0 ±2.0*'Basal
88.5 ±5.7 89.1 ±5.0 89.4 ±3.7Month
3109.91
±4.70*105.64±4.06'1.46
±0.37"0.52±0.096.17
±1.97*'1.98±0.60'7.07
±1.81"2.34±0.49'0.29
±0.160.25±0.14'96.0
±1.9*'89.3
±5.14110.36
±3.32*107.09±4.591.33
±0.38"0.52±0.155.72
±1.52*'2.08
±0.726.62
±2.05"2.44±0.59'0.28
±0.200.22±0.12'96.0
±2.2"91.3±3.7'5108.73
±4.17«104.73±5.02'1.43
±0.77"0.50±0.164.99
±1.12**1.77±0.37'6.05
±1.30*'2.20±0.38'0.26
±0.140.21±0.10'95.8
±1.8"90.1±4.96111.91
±2.59"109.09±2.741.54
±0.38"0.51±0.115.55
±1.36"1.89±0.37'6.74
±1.34*'2.45±0.41'0.29
±0.160.24±0.13'95.8
±2.1"90.4±5.2
'See footnote to Table 3 for further information and key to symbols.
mechanism of action, one which may be independentof PTH (42, 45-47); 2) increased renal filtered load ofionized calcium (46); 3) decreased bicarbonate deliveryto the renal tubules, which decreases renal tubular calcium reabsorption (41, 43, 48); 4} suppressed renal response to PTH independent of PTH concentration (33,48, 49); and 5) decreased 1,25-dihydroxycholecalciferolconcentration, which may reduce tubular reabsorptionof calcium independently of PTH (50). In contrast toresults in other species, this study demonstrated thatpartial to complete compensation in the treated catsoccurred by the end of the experiment despite continuing acidosis. This may be due to the ability of thefeline kidney to adapt to or correct those changes induced by metabolic acidosis.
There was no significant difference in average dailyfecal calcium excretion between groups during the study.However, in the last 3 mo there was a significant decrease in fecal calcium excretion in treated cats, and asignificant decrease in mo 5 and 6 in control cats. Because this was a consistent finding affecting all minerals measured in this study, this was thought to bedue to an overall decrease in fecal output from decreased food consumption, rather than evidence of increased intestinal absorption. The percent digestiblecalcium, which was significantly lower only in mo 4in the treated cats compared to control cats and negative relative to mo 0, was interpreted as a reductionin intestinal absorption of calcium as a result of dietaryacidification (2, 8-10). This could also represent increased intestinal endogenous calcium secretion due toincreased ionized calcium in the treated cats (51), butendogenous mineral secretion could not be measuredwith the dietary balance methods used in this study.
In the treated cats, decreased plasma 1,25-dihydroxy
cholecalciferol concentration was considered to be apotentially important factor contributing to the lowerdigestibility of calcium (34, 52-54). Studies have demonstrated that 1,25-dihydroxycholecalciferol levels aredecreased in CMA, and that this may be due to decreased levels of PTH, decreased activity of PTH, ormay occur independently of the effects of PTH (55, 56).There may be impaired production of 1,25-dihydroxycholecalciferol due to increased ionized calcium levels(53, 58) or H+ concentrations, or to increased degra-
•o—
I I
0.0
Tim« (month)
FIGURE 4 The effect of chronic dietary acidification using1.5% ammonium chloride on chloride balance in adult cats.Values are mean ±SEM,n = 11 cats in each group. 'Significant difference, P < 0.05, between groups. °Significantly
different P < 0.05, from mo 0.
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CHRONIC DIET ACID AND MINERAL METABOLISM IN CATS 911
TABLE 7
Effects of chronic dietary acidification on potassium metabolism in adult cats1
0 12Plasma
potassium, mmol/1Acidified 3.96 ±0.43 4.09 ±0.33 4.13 ±0.36Basal
4.21 ±0.45 4.16 ±0.42 4.10 ±0.16Urinaryfractional excretion of potassium, %
Acidified 14.84 ±4.09*2 14.53 ±3.46*2 12.90 ±3.59'Basal
11.32 ±2.28 12.12 ±2.29 12.87 ±2.41Averagedaily urinary excretion of potassium, mmol/kg body wt
Acidified 2.34 ±0.66 2.65 ±0.35* 2.27 ±0.47Basal2.28 ±0.60 2.24 ±0.63 2.06 ±0.60Average
daily intake of potassium, mmol/kg body wtAcidified 2.94 ±0.53 2.67 ±0.57 2.44 ±0.49'Basal
3.01 ±0.67 2.83 ±0.63 2.58 ±0.51fAverage
daily fecal excretion of potassium, mmol/kg body wtAcidified 0.39 ±0.20 0.34 ±0.17 0.28±0.11»Basal
0.42 ±0.26 0.36 ±0.25 0.30±0.11'Digestible
potassium, %Acidified 87.2 ±5.8 87.6 ±4.6 88.6 ±4.0Basal
86.4 ±7.8 88.1 ±6.7 88.6 ±3.6Month
33.97
±0.283.93±0.32»12.96
±2.83»12.99±2.17*2.06
±0.621.84±0.58'2.23
±0.57»2.41±0.51'0.29
±0.16'0.31±0.18»87.1
±6.187.3±7.444.02
±0.334.02±0.2812.28
±1.85'12.74
±2.122.01
±0.351.94±0.47'2.09
±0.65'2.51±0.61'0.23
±0.16'0.25±0.11»89.2
±5.390.2±3.1'53.85
±0.343.80±0.28'12.95
±2.1313.15±3.45»1.77
±0.33»1.72±0.35'1.91
±0.41"2.27±0.39»0.22
±0.12»0.25±0.08'88.8
±4.489.2±3.064.30
±0.57»3.99
±0.3713.24
±3.1613.12±2.70'1.90
±0.47»1.79±0.36*2.13
±0.42"2.52±0.42»0.22
±0.08*'0.28±0.08'89.9
±2.7'89.0
±3.0
'See footnote to Table 3 for further information and key to symbols.2For acidified diet group, n = 8.
dation or excretion of 1,25-dihydroxycholecalciferol inCMA (2, 34, 52-54, 56-58).
The treated cats had a significantly negative net calcium balance relative to baseline (mo 0) in mo 1-3,significantly lower balance compared to control cats inmo 4, and a trend towards adaptation to baseline calcium balance in mo 4-6. This period of adaptation afternegative calcium balance differs from other studies donein humans, rats, dogs and sheep (1-9). Lower daily calcium balance is due to increased urinary calcium loss
08_
•0.6
Tim« (month)
FIGURE 5 The effect of chronic dietary acidification using1.5% ammonium chloride on potassium balance in adult cats.Values are mean ±SEM,n = 11 cats in each group. 'Significant difference, P < 0.05, between groups. °Significantlydifferent, P < 0.05, from mo 0.
and decreased intestinal calcium absorption in cats withCMA.
In general, plasma phosphorus and renal and intestinal handling of phosphorus were affected less by chronicdietary acidification in this study despite changes incalcium and 1,25-dihydroxycholecalciferol concentrations. Some investigators have reported unchanged bloodphosphorus concentration in CMA, whereas others havereported lowered concentration in humans (10) or rats(2).
The daily potassium balance was significantly decreased in the cats fed 1.5% NH4C1 relative both tobaseline and to control cats. Decreased balance couldhave resulted from urinary potassium loss withoutchanges in intestinal absorption. Studies have indicatedthat CMA is paradoxically a potent stimulus for renalpotassium excretion and may lead to potassium depletion (6, 11, 12, 59). The cats in the present study, however, had plasma potassium concentrations which remained in the normal range (23) and were not differentbetween groups (Table 7). Kaliuresis is often associatedwith NH4Cl-induced metabolic acidosis and may bedue to: Õ)decreased filtered bicarbonate and increasedurine flow and distal sodium delivery, which will increase Na-K cation exchange; 2}stimulated aldosteronesecretion; 3) increased tubular chloride concentrationand increased distal fluid delivery; 4} increased concentration of distally impermeate or nonreabsorbableanions such as phosphate or sulfate, which will increase tubular flow and increase luminal electronega-tivity in the distal nephron; 5) increased filtered loadof potassium to the kidney; and/or 6) kaliuresis concomitant with magnesium loss (11-13, 60-62). Al-
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912 CHING ET AL.
TABLE8
Effects of chronic dietary acidification on sodium metabolism in adult cats1
01Plasma
sodium,mmol/1Acidified153.09 ±2.51 152.00 ±2.45Basal152.51 + 2.80 152.82 ±4.73Urinary
fractional excretion of sodium,%Acidified0.40 ±0.10» 0.50±0.10"Basal
0.31 ±0.08 0.34 ±0.04Averagedaily urinary excretion of sodium,mmol/kgAcidified
2.13 ±0.53 3.14 ±0.39"Basal
2.29 ±0.62 2.32 ±0.66Averagedaily intake of sodium, mmol/kg bodywtAcidified
4.05 ±0.73 4.16 ±0.89Basal4.14 ±0.92 3.90 ±0.872150.73
±2.53'152.36
±4.780.43
±0.110.37±0.07'body
wt2.67±0.59*'2.17
±0.643.81
±0.763.55±0.71'Month
3150.82
±4.12149.82±2.990.41
±0.120.36±0.052.38
±0.751.96±0.61'3.48
±0.89'3.32±0.70«4149.46
±4.99«151.55
±4.080.40
±0.090.35±0.072.30
±0.452.03±0.513.26
±1.01«3.46±0.84*5150.64
±4.27«153.46
±3.480.41
±0.230.34±0.11.95
±0.351.77±0.36«2.98
±0.64«3.12±0.53«6149.91
*3.86«151.91
±5.090.46
±0.10-0.35
±0.082.22
±0.56*1.83±0.40«3.31
±0.66'3.47±0.58'Average
daily fecal excretion of sodium, mmol/kg bodywtAcidified0.60 ±0.34 0.48 ±0.29'Basal
0.59 ±0.28 0.45 ±0.25Digestiblesodium,%Acidified
85.4 ±8.2 88.8 ±5.8*Basal
86.2 ±6.6 88.9 ±5.1Dailysodium balance, mmol/kg bodywtAcidified
1.32 ±0.60 0.54 ±0.47"Basal
1.27 ±0.50 1.13 ±0.520.40
±0.20'0.40±0.17*89.8
±4.7«88.6
±4.20.74
±0.40*0.97
±0.690.37
±0.19'0.41±0.20'89.6
•+3.6*88.0
±5.40.72
±0.27*0.96
±0.460.36
±0.26'0.36±0.21«89.2
±5.9«89.9±4.7«0.48
±0.67*'1.07
±0.770.33
±0.16«0.32±0.17*89.3
±4.2«89.7
±5.70.70
±0.47«1.04
±0.630.37
±0.20'0.42±0.23*89.2
±4.8«87.4
±7.60.72
±0.34"1.23
±0.64
'See footnote to Table 3 for further information and key to symbols.
dosterone levels were not measured in this study, butother studies have indicated that CMA stimulates al-
dosterone secretion, which maintains inappropriatelyhigh urinary potassium excretion even in the presenceof potassium depletion (12, 63, 64). Increased digestibility in mo 6 relative to baseline in the treated catsmay have contributed to the return of potassium balance to baseline.
Magnesium metabolism in this study was moderately affected by dietary acidification. The combinationof increased urinary loss of magnesium with marginallydecreased intestinal magnesium absorption in the treatedcats could cause lower magnesium balance in severalmonths. By mo 6, magnesium balance in the treatedcats had returned to baseline.
There are few studies on the effects of CMA on magnesium metabolism in humans or experimental animals (2, 65). CMA appeared to affect renal handling ofmagnesium more significantly than its intestinal absorption in this study. Acute metabolic acidosis hasbeen reported to increase magnesuria, but other factorsin addition to or subsequent to acidosis may regulatemagnesium excretion (13). The renal filtered load ofmagnesium may be increased as a result of increaseddietary intake, or redistribution of Mg+ + from intra -
cellular compartments or from skeletal and soft tissuestores (13). Low parathyroid hormone concentration orphosphate depletion can decrease renal magnesiumreabsorption, resulting in increased urinary excretion(12, 13, 66). The PTH and phosphorus levels in bothgroups of cats were not significantly different and wereunlikely to have contributed to urinary magnesium loss.Magnesuria may have resulted secondary to elevated
blood ionized calcium concentration and hypercalci-uria in the treated cats (13).
Sodium metabolism was minimally affected bychronic dietary acidification. Plasma sodium concentration and urinary excretion of sodium for both groupsremained within normal reference ranges (23). Although there were significant increases in urinary sodium excretion in the treated cats in mo 1 and 2, theFENafor all cats was less than 1% (Table 8), indicatingnormal renal tubular function throughout the study(23). Moderate diuresis and natriuresis in the treatedcats during the first 2 mo of the study most likelyresulted from decreased sodium and water reabsorptionsecondary to reduced filtered bicarbonate, increased tubular concentration of chloride and increased renal tubular fluid flow (11, 12). There were no significant treatment effects on the intestinal absorption of sodium.
Plasma chloride concentration was increased in thetreated cats in all months of treatment (Table 6), butwas within normal reference ranges reported for cats(23). Increased urinary excretion of chloride and dailychloride balance in the treated cats were attributableto the ingestion of NH4C1 and increased dietary intakeof chloride. It is unknown why the fractional excretionof chloride (FEa) was higher in mo 0 compared to thecontrol cats, but it is important to note that once thecats began consuming the NH4Cl-supplemented diet,their FEC1 increased approximately twofold over thebaseline and control values. This is consistent withother in vivo and in vitro studies (11, 67).
Overt detrimental physical effects did not develop inthe treated cats as a result of dietary acidification andalterations in their acid-base and mineral metabolism.
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CHRONIC DIET ACID AND MINERAL METABOLISM IN CATS 913
25 -,
55-,
012 3456Time (month)
FIGURE 6 Plasma parathyroid hormone (A) and 1,25-di-hydroxycholecalciferol (calcitriol) (B)concentrations in adultcats fed 1.5% ammonium chloride for 6 mo. Values are mean±SEM,n = 11 cats in each group. 'Significant difference, P< 0.05, between groups. °Significantly different, P < 0.05,
mo 0.
The differences in this study may be statistically significant, but may not reflect clinical importance. Prolonged calcium loss may potentiate the developmentof osteoporosis. Chronic potassium depletion in catshas been reported to cause polymyopathy and potentiate the development of nephropathy or exacerbatechronic renal insufficiency (68, 69). It is unlikely thatthe modest change in potassium balance in acidoticcats with normal renal function and normal dietaryintakes of potassium would result in adverse long-termeffects, but there is little data to show how long catsare capable of remaining in abnormal acid-base and
mineral balance. Increased urinary magnesium excretion may predispose cats to form insoluble urinary tractsstruvite (magnesium-ammonium-phosphate) calculi or
crystals, which could lead to the development of feline
urologie syndrome (15). However, a recent study demonstrated that urethral obstruction and the formationof struvite crystals in cats with experimental and natural disease were not necessarily associated with increased urinary magnesium concentrations (70). Nevertheless, the lower urinary pH in the acidotic cats wouldhelp prevent the formation of these crystals. It is unknown how long these cats can remain in negative orlower mineral balance before clinically detrimental effects may develop. The marginal acid-base status and
mineral balance of cats fed 1.5% NH4C1 or other acidifying diet may be exacerbated by concurrent clinicaldisease. Apparent adaptation in mineral metabolismwas observed in the treated cats in the fifth or sixthmonth of dietary acidification. This is in contrast toother species, and it is unknown whether adaptationwould continue until baseline balance is established.Adaptation in cats may reflect unique renal mechanisms or an increased ability to buffer chronic acidstress.
ACKNOWLEDGMENTS
The authors are grateful to Marlene Gerlach for herhelp and guidance in the laboratory analyses. We wishto thank Maggie Voorhees for animal care and technicalassistance with procedures performed during the study.
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