Urolithiasis is an economically significant disease seen commonly in castrated male ruminants, which can lead to partial or complete urinary obstruction, representing a medical emergency.1 The most common sites of urolith formation are the distal sigmoid flexure and urethral process. Early castration is a known risk factor for obstructive urolithiasis, resulting in smaller urethral diameter in calves and lambs.2,3 Urolithiasis is a multifactorial disease process influenced by anatomy, body water balance, urinary pH, and diet.
In goats, uroliths are most commonly composed of magnesium ammonium phosphate (struvite), calcium carbonate, calcium phosphate (apatite), or amorphous magnesium calcium phosphate.4,5 Diet and urinary pH represent variables that can be manipulated for management of this disease. Struvite and apatite uroliths have been associated with high grain rations. Calcium carbonate uroliths were shown to be formed in Boer goats fed legume-based diets.6 Uroliths that form in alkaline urine are struvite, apatite, and calcium carbonate, whereas silicate and calcium oxalate have not been documented to be affected by urine pH.7
Numerous treatment modalities exist for obstructive urolithiasis, with the goal being to establish urine flow. Medical management focuses on administration of urinary acidifiers, resulting in dissolution of uroliths that are soluble in acidic urine. However, in complete obstructive urolithiasis, acidification may not dissolve uroliths quickly enough to be therapeutic. Surgical management may then be necessary, including the use of procedures such as removal of urethral appendage,8 tube cystostomy,9 perineal urethrostomy,10 and bladder marsupialization. Tube cystostomy followed by urinary acidification for dissolution of the remaining stones represents an efficacious treatment method for urolithiasis.8,9
Manipulation of urine pH represents a cornerstone of medical management of urolithiasis. Commonly utilized urinary acidifiers include ammonium chloride (AC) and Walpole solution. Ammonium chloride is regarded as a mainstay treatment for struvite and apatite stone dissolution. However, a previous study11 identified an association between administration of AC and an increased urinary fractional excretion of calcium (FECa) in goats fed orchard grass hay. This demonstrated a potential increased risk in the formation of calcium-based uroliths in goats administered AC. In addition, AC is poorly palatable, which can influence owner compliance and administration success. D,L methionine (MET), a sulfur-containing amino acid, is utilized as a rumen bypass protein, which can result in improved growth performance, feed conversion, and wool production and increased milk yield.12 Additionally, the use of methionine for urinary acidification has well-documented success in humans and cats.13,14 D,L methionine induces aciduria through the metabolism of sulfur, which is excreted as sulfuric acid into the urine.15 Pilot project preliminary data showed that an oral dose of 200 mg/kg MET every 24 hours resulted in a significant decrease in urine pH from baseline in healthy goats.16
The objectives of this study were to measure urine pH in goats that were administered AC or MET, to compare the FECa in goats treated with AC or MET, and to measure acid-base status throughout the trial period. We hypothesized that the use of orally administered AC and MET would result in urinary acidification, MET would alter FECa less than AC, and neither treatment would induce systemic metabolic acidosis.
Methods
Animals
Twelve Boer-cross wethers were enrolled from a single farm located within 15 miles of Starkville, Mississippi. Goats were housed together in a temperature-controlled facility at the College of Veterinary Medicine at Mississippi State University. All sampling occurred from September through November 2022. An acclimation period of 14 days was given to allow for adjustment to the environment. All wethers had been castrated at approximately 3 weeks of age. Wethers were between 5 and 6 months of age (median, 5.3 months), weighing 14.5 to 29.5 kg (median, 21.8) with body condition scores of 4 to 5.5/9 (median, 5). Physical examinations were performed at intake and every treatment day for the duration of the study. A pelleted ration was administered once daily, to 6 goats at a time, at a rate of 0.45 kg/head/d of a pelleted ration (20% Hi-Fiber Dairy Pellet; Ware Milling). This ration was selected based on the request of the owner of the goats, who wished for them to stay on this feed during the study. Grass hay and water were offered ad libitum and refreshed twice daily. Feeding of the pelleted ration occurred at 6:00 am every day of the study period. All animal feeding, handling, sample collection, and immediate sample analysis were performed by a single person (CEN). This study was approved by the Mississippi State University IACUC (protocol #22-348).
Study design
The study was prospective, randomized, and crossover in design. Goats were randomized equally into 2 treatment groups using a random number generator. Goats were administered AC (99% free AC; AniMed) or MET (VET-Pharmaceuticals) by mouth once daily at a dose of 200 mg/kg for 14 days. Each day, the medication was given at 7 am. The AC product was in powder form, whereas the MET product was tablet form. D,L methionine tablets were ground into a powder using a mortar and pestle. Each drug was then dissolved in 10 mL of water and administered with an oral dosing syringe (60-mL catheter tip syringe; Coviden). A washout period of 7 days was used between trials prior to crossover.
Sampling
During each trial period, blood and urine samples were collected every 48 hours. These samples were collected approximately 5 hours after medication administration. The nadir in urine pH has been shown to occur 5 to 7 hours after AC administration.17 Baseline samples were collected at day 0 prior to administration of treatment for each trial.
Blood gas analysis
Blood samples were collected via jugular venipuncture into lithium heparin tubes (Vacutainer Heparin Tube; Becton Dickinson; 4-mL draw) to provide anticoagulation. Blood gas analysis (iSTAT; Abbott Point of Care Inc) was performed within 5 minutes of sample collection utilizing CG4+ cartridges, which had been refrigerated until 10 minutes prior to use. The blood gas analyzer was calibrated according to manufacture instructions. The results of interest that were recorded included blood HCO3- and blood pH. The remaining blood sample was centrifuged at 3,000 rpm for 15 minutes to allow collection of 0.5 mL of plasma. Plasma samples were stored at −80 °C for electrolyte (Na, K, Cl, Ca, Ph) levels to be determined. Plasma analysis occurred at Texas A&M Veterinary Diagnostic Laboratory (DxC 700AU; Beckman Coulter).
Urine collection
Goat wearing the urinary collection device fashioned from a teaser ram harness (No-Mate Teaser Harness; Rurtec).
Citation: American Journal of Veterinary Research 85, 11; 10.2460/ajvr.24.04.0097
Statistical analysis
The outcomes of primary interest were FECa and urine pH. Additional outcomes of interest included blood pH and blood HCO3-. Sample size calculations using G*Power, version 3.1.9.2, determined that 12 goats were needed to detect a difference of 2% in fractional excretion levels of calcium in paired urine samples collected from goats treated with either MET or AC in a crossover study.16 The assumptions used for the calculations included an α level of 0.05, power of 0.95, correlation between the 2 sample points of 0.5, a 2-tailed test, and SDs of 1.68% for treated and control groups, respectively.11 Further calculations using G*Power, version 3.1.9.2, determined that a sample size of 11 was needed to detect a 1-U drop in urine pH in response to treatment with MET or AC. The assumptions used for the calculations included a 1-tailed test, an α of 0.05, a power of 0.95, and an SD of 0.91 U.18 Given the higher sample size required for a 2% change in fractional excretion levels of calcium, a sample size of 12 goats was adopted.
The effect of treatment and day of administration of treatment on urine pH, FECa, blood pH, and blood HCO3- was assessed using linear mixed models with PROC MIXED in SAS for Windows, version 9.4 (SAS Institute Inc). Separate models for each outcome were fit with treatment, day, and their interaction as fixed effects with Kenward-Roger approximation for the degrees of freedom specified. Goat identity and trial were included as random effects. Repeated measures of goat identity within trial for the different sample days were specified in a repeated statement with a first-order autoregressive covariance structure. Similar models for each outcome were fit with data restricted to either trial 1 or trial 2. In these models, goat identity was included as a random effect and in a repeated statement with a first-order autoregressive covariance structure. If the treatment-day interaction term was not significant, it was removed, and the model was refit. A Dunnett multiple comparison test was used to compare day 0 to the other sample days when the outcome was significant. To test that the washout period was sufficient, separate linear models for each outcome with trial as a fixed effect were fit with data limited to day 0 values. Visual assessment of the distribution of conditional residuals was used to determine if the assumptions of normality and homoscedasticity for each of the statistical models had been met. These assumptions were not met for the models assessing FECa. Consequently, the values were log10 transformed and the models refit. Statistical significance was determined using an α level of 0.05 for all models. Least squares means (LSM), 95% CIs, and the associated P value are reported for pairwise comparisons.
Results
Twelve goats were enrolled, and all completed the study. There were no apparent health events, including incidents of inappetence, gastrointestinal disturbance (diarrhea, bloat), urinary obstruction, or other abnormal events.
Urine pH
There was no significant difference in urine pH between treatment groups (P = .12); however, there was a significant day effect (P < .01) for both treatment groups. Urine pH on day 6 (LSM, 7.49; P < .01; 95% CI, 6.44 to 8.54), 8 (LSM, 7.78; P = .01; 95% CI, 6.73 to 8.83), and 10 (LSM, 7.53; P < .01; 95% CI, 6.49 to 8.58) was significantly lower than on day 0 (LSM, 8.23; 95% CI, 7.18 to 9.28) (Figure 2). Notably, in trial 1 alone, goats treated with AC had a numerically lower urine pH (LSM, 7.53; 95% CI, 7.32 to 7.75) than goats treated with MET (LSM, 7.82; 95% CI, 7.61 to 8.04), but this effect did not reach statistical significance (P = .06). In trial 1, a day effect was present for days 6 (LSM, 7.16; P < .01; 95% CI, 6.82 to 7.50) and 10 (LSM, 7.08; P < .01; 95% CI, 6.73 to 7.42) when compared to day 0 (LSM, 8.19; 95% CI, 7.85 to 8.54) and adjusted for the effect of treatment groups (Figure 2). In trial 2, urine pH was significantly different from baseline on day 6 (LSM, 7.82; P < .01; 95% CI, 7.67 to 7.97), day 8 (LSM, 7.88; P < .01; 95% CI, 7.73 to 8.03), day 10 (LSM, 7.99; P = .04; 95% CI, 7.84 to 8.14), and day 14 (LSM, 7.99; P = .03; 95% CI, 7.84 to 8.14) when compared to day 0 (LSM, 8.27; 95% CI, 8.12 to 8.42) and adjusted for the effect of treatment groups (Figure 2).
Scatterplots of urine pH of individual goats treated with methionine (MET) (circles) or ammonium chloride (AC) (triangles) in trial 1 (A; n = 6 per group) and trial 2 (B; n = 6 per group) and with data from both trials combined (C; n = 12 per group). For each group of data points on each day, the line among the points represents the arithmetic mean. On each graph, a line is placed at pH = 6.5, the pH target for clinically relevant urinary acidification when goats are treated for urolithiasis. Although nearly significant in trial 1, the effect of treatment on urine pH was not significant in trial 1 (P = .06), trial 2 (P = .66), or in both trials combined (P = .12). There was a significant effect of trial day on urine pH in trial 1 (P < .01) and trial 2 (P < .01) and in both trials combined (P < .01). In trial 1, urine pH was significantly different from baseline on day 6 (P < .03) and day 10 (P < .01) (A). In trial 2, urine pH was significantly different from baseline on day 6 (P < .01), day 8 (P < .01), day 10 (P = .04), and day 14 (P = .03) (B). With data for both trials combined, urine pH was significantly different from baseline on day 6 (P < .001), day 8 (P = .08), and day 10 (P < .01) (C). Comparisons of least squares means from linear mixed models were used to determine statistical significance.
Citation: American Journal of Veterinary Research 85, 11; 10.2460/ajvr.24.04.0097
Blood pH
A significant effect of treatment (P = .77) or day (P = .11) was not detected for blood pH.
Blood HCO3-
There was a significant day effect (P = .04) for blood HCO3-, where day 6 (LSM, 24.83; P = .05; 95% CI, 23.48 to 26.17) was significantly lower than on day 0 (LSM, 26.14; 95% CI, 24.80 to 27.49) when adjusted for the effect of treatment groups. In trial 1 alone, the AC group had significantly lower blood HCO3- (LSM, 24.03; P = .05; 95% CI, 22.74 to 25.31) than MET (LSM, 25.83; 95% CI, 24.55 to 27.12) when adjusted for the effect of day. There was also a significant day effect (P = .02) when adjusted for the effect of treatment. Blood HCO3- on days 6 (LSM, 23.90; P < .01; 95% CI 22.67 to 25.13), 10 (LSM, 24.38; P = .03; 95% CI, 23.16 to 25.61), and 14 (LSM, 24.42; P = .03; 95% CI, 23.19 to 25.64) was significantly lower than day 0 (LSM, 26.37; 95% CI, 25.14 to 27.59).
Fractional excretion of calcium
A significant treatment (P = .41) or day effect (P = .69) was not detected on FECa over the duration of the AC and MET trials (Figure 3). However, in trial 1, increased FECa was present in some goats on days 6, 8, and 10 (Figure 3).
Scatterplots of urinary fractional excretion of calcium (FECa) for individual goats treated with MET (circles) or AC (triangles) in trial 1 (A; n = 6 per group) and trial 2 (B; n = 6 per group) and with data from both trials combined (C; n = 12 per group). For each group of data points on each day, the line among the points represents the arithmetic mean. Least squares means of log10 FECa were used for data analysis.
Citation: American Journal of Veterinary Research 85, 11; 10.2460/ajvr.24.04.0097
Blood electrolytes (calcium, phosphorus, sodium, potassium, chloride) and urinary fractional excretions (phosphorus, sodium, potassium, chloride) were not analyzed for statistical inferences in this study. These values are available in (Supplementary Material S1).
Discussion
Information regarding the use of AC or MET as a urinary acidifier in the small ruminant population is limited. It is important to note that neither drug bears a label for the prevention or treatment of urolithiasis. Dosing regimens utilized in this study were extrapolated from previous data. Regarding MET dosing, we are not aware of published research describing the use of MET as a urinary acidifier for small ruminants. A pilot dose-response study16 was performed and demonstrated urine acidification (urine pH ≤ 6.5) when healthy goats were given orally administered MET at a dose of 200 mg/kg once daily. For AC, a dose of 200 mg/kg administered orally once daily is recommended in veterinary drug formularies and texts,19,20 and this dose has been proposed to achieve adequate acidification to treat or prevent urolithiasis.20,21 It is desirable to utilize the lowest dosage necessary to achieve urine acidification to prevent the induction of metabolic acidosis and subsequent adverse clinical effects.
The average urine pH of small ruminants on a forage diet is alkaline. A previous in vitro study22 indicated that struvite dissolution is correlated to lowering urine pH. A pH value of ≤ 6.5 increases the dissolution rate and has been suggested to be a threshold value for dissolution.22 In this study, in trial 1, multiple goats achieved a urine pH of 6.5 or less when treated with AC. This contrasts with Mavangira et al,11 where this dosage did not lower urine pH in their population of 3 goats. Additionally, in the present study, urine pH was measured using a calibrated pH meter, potentially yielding a more accurate result than other methods of quantifying pH, such as paper strips. In the present study, in trial 1, a urine pH of less than 6.5 was measured in 2 of 6 goats on day 6 and 2 of 6 goats on day 10 in the AC group. For the MET group, in trial 1, urine pH was less than 6.5 in 2 of 6 goats on day 6 and 2 of 6 goats on day 10 in trial 1. On each day when urine pH less than 6.5 was measured in some goats, it was not always the same goat that had urine pH less than 6.5.
While both AC and MET treatments were able to acidify the urine of some goats in trial 1, urine pH did not decrease below 7.0 in any goat in trial 2. Similarly, in trial 1, a treatment and day effect on blood HCO3- was identified that was not seen in trial 2. This difference in response to treatment between the 2 study trials was unexpected. In our hospital, caprine patients being treated for urolithiasis typically develop acidic urine (pH < 7.0) when treated with AC at doses of 100 to 200 mg/kg. Similarly, our earlier pilot study indicated that 200 mg/kg of MET could acidify urine.16 Thus, we expected that the doses of AC and MET used in this study would result in urinary acidification of most if not all treated goats. Although urine pH was not acidified in all goats in either treatment group, urine pH was significantly decreased from baseline on in urinary pH on days 6, 8, and 10 in comparison to day 0.
The failure of urine to become acidic following treatment of some goats in trial 1, and in all goats in trial 2, may have been due to dietary factors. The prepartum feeding of anionic salts, such as AC, to create a ration with a low cation anion difference (DCAD) in order to prevent postparturient hypocalcemia is commonplace in the dairy industry, and treated cows develop acidic urine as a result of this treatment.23,24 Relevant to the current study, a low-DCAD diet has been associated with an increase in renal excretion of calcium in castrated sheep.25 It is well known that the cation content of forages must be monitored when DCAD rations are formulated for dairy cows. The inclusion of forages containing high concentrations, of cations such as K+ or Na+, can make it difficult to obtain the negative DCAD required to induce the mild acidification needed to change calcium homeostasis and prevent postpartum hypocalcemia.26 The DCAD of the pelleted ration provided to the goats in this study was positive at 102.39 mEq/kg. The failure of several goats in this study to develop acidic urine may have been due to a positive ration DCAD, which may have antagonized the effects of the urine-acidifying drugs. Differences in forage intake could have led to different effects of diet on treatment among the goats in trial 1, perhaps explaining the acidic urine measured in some goats. We acknowledge that a nontreated control group of goats would have been useful in determining the effects of the DCAD of this specific ration alone.
Another potential explanation for the failure of goats in trial 2 to develop acidic urine could be that goats in trial 2 did not receive the full dose of either treatment. Administration of AC can be difficult and a limiting factor to owner compliance, presumably due to poor palatability.19 However, we do not think this is likely, because every effort was made to ensure consistent administration to all goats. In both trials, the investigator administering treatments (CEN) watched carefully to make sure goats did not spit out the medication. However, it must be acknowledged that oral administration did not guarantee that the entire dose of drug reached the rumen. Perhaps our findings would have been different if the drugs had been administered by ororuminal tubes. However, we wanted to test the route of administration that would have been used in the clinic or in a farm setting. Subjectively, we found MET to be significantly easier to administer, presumably due to increased palatability in comparison to AC. Additionally, MET tablets have been reported to be voluntarily consumed by goats.16
In our clinical experience, we are often successful at inducing aciduria utilizing a 200-mg/kg dose of AC in goats hospitalized for urolithiasis. Under the conditions of this study, this did not occur in all goats. These differences might be due to the effects of disease, including azotemia and inappetence of hospitalized animals with urolithiasis, versus the healthy population of goats used in this study. Goats who are anorexic may ingest fewer dietary cations, allowing AC to exert a more acidifying effect than goats who are consuming their rations readily.
Administration of AC has been correlated with increased FECa in goats, which could predispose them to forming calcium-based uroliths.11 In dogs, an increased excretion of calcium in the urine has been documented as a risk factor for calcium-based urolith formation.27 Though not statistically significant, FECa was higher in goats administered AC, which is best described in Figure 3. Acidosis is associated with an increased FECa.28 This increase in FECa aligns with the data showing significant urine pH decrease occurring on days 6, 8, and 10 and also being a stronger effect in trial 1. However, it is probable that our lack of more substantial acidification prevented a statistically significant difference in FECa.
The results of this study suggest that healthy goats consuming a positive DCAD pelleted ration can respond differently than expected when treated with the specified urinary acidifiers. This is likely relevant to efforts to prevent urolithiasis in male goats. Ration analysis may be necessary to optimally acidify the urine of healthy goats at risk for urolithiasis, and future research should investigate the relationship between dietary DCAD and response to urinary acidification in goats. Further research should also evaluate urinary pH, blood pH, and FECa in goats with urolithiasis following treatment with MET or AC. We suspect that the findings of our study may be amplified if clinically affected animals were placed under the same conditions. In addition, evaluation of the effects of higher doses of these medications could be explored given that little research has focused on the use of MET for urinary acidification in small ruminants.
In conclusion, under the conditions of this study, there was no significant difference between the effects of AC and MET on urinary pH, blood pH, or FECa in healthy goats. However, in the first trial, both AC and MET were capable of acidifying urine in some goats on days 6, 8, and 10 post initiation of treatment. Doses of AC and MET previously recommended to acidify urine to prevent or treat urolithiasis did not lead to urinary acidification in some goats. Forage cation concentrations may have influenced the response of goats to treatment expected to acidify their urine. This study provides evidence that MET can acidify caprine urine. The lack of treatment effect on FECa may have been due to failure of treatment to induce urine pH < 7.0 in multiple goats. Future research utilizing AC and MET should consider the DCAD of the diet fed as we believe that the DCAD can antagonize the effects of urinary acidifier administration. Further research is needed to confirm doses of AC or MET that can consistently acidify urine in healthy goats in order establish effective methods to prevent caprine urolithiasis.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
The authors thank the Laboratory Animal Resources and Care Unit at the College of Veterinary Medicine for their care of the animals during the study period. They greatly thank Dr. Jim and Heather Brett for facilitating this research through the use of their goat herd.
Disclosures
The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.
Funding
Funding was provided through a grant supplied by Mississippi State University College of Veterinary Medicine by appointed USDA Formula Funds.
ORCID
C. E. Neal https://orcid.org/0009-0007-4540-4833
References
- 1.↑
Radostits OM, Blood DC, Gay CC. Diseases of the urinary system. In: Constable PD, Hinchcliff KW, Done SH, Grünberg W, eds. Veterinary Medicine, a Text Book of the Disease of Cattle, Sheep, Goats, Pigs and Horses. 11th ed. Baillere Tindall; 1994:450–455.
- 2.↑
Marsh H, Safford JW. Effect of deferred castration on urethral development in calves. J Am Vet Med Assoc. 1957;130(8):342–344.
- 3.↑
Bani Ismail ZA, Al-Zghoul MF, Al-Majali AM, Khraim NM. Effects of castration on penile and urethral development in Awassi lambs. Bulg J Vet Med. 2007;10(10):29–34.
- 4.↑
Jones ML, Miesner MD. Urolithiasis. In: Anderson DE, Rings DM, eds. Current Veterinary Therapy: Food Animal Practice. 5th ed. Saunders; 2009:322–325.
- 5.↑
Jones ML, Gibbons PM, Roussel AJ, Dominguez BJ. Mineral composition of uroliths obtained from sheep and goats with obstructive urolithiasis. J Vet Intern Med. 2017;31(4):1202–1208. doi:10.1111/jvim.14743
- 6.↑
Jones ML, Dominguez BJ, Deveau MA. An experimental model for calcium carbonate urolithiasis in goats. J Vet Intern Med. 2018;32(3):1268–1273. doi:10.1111/jvim.15061
- 7.↑
Pérez-García I, Rivadeneyra M, Ramos-Cormenzana A. The influence of pH on struvite formation by bacteria. Chemosphere. 1989;18(8):1633–1638. doi:10.1016/0045-6535(89)90053-2
- 8.↑
Mejia S, McOnie RC, Nelligan KL, Fubini SL. Small ruminant urinary obstruction: decision trees for treatment. J Am Vet Med Ass. 2022;260(S2):64–S71.
- 9.↑
Ewoldt JM, Anderson DE, Miesner MD, Saville WJ. Short-and long-term outcome and factors predicting survival after surgical tube cystostomy for treatment of obstructive urolithiasis in small ruminants. Vet Surg. 2006;35(5):417–422.
- 10.↑
Riedi AK, Nathues C, Knubben-Schweizer NK, Meyland M. Variables of initial examination and clinical management associated with survival in small ruminants with obstructive urolithiasis. J Vet Intern Med. 2018;32(6):2105–2114. doi:10.1111/jvim.15336
- 11.↑
Mavangira V, Cornish J, Angelos J. Effect of ammonium chloride supplementation on urine pH and urinary fractional excretion of electrolytes in goats. J Am Vet Med Assoc. 2010;237(11):1299–1304. doi:10.2460/javma.237.11.1299
- 12.↑
Toledo MZ, Baez GM, Garcia-Guerra A, et al. Effect of feeding rumen-protected methionine on productive and reproductive performance of dairy cows. PLoS One. 2017;12(12):e0189117. doi:10.1371/journal.pone.0189117
- 13.↑
Siener R, Struwe F, Hesse A. Effect of L-methionine on the risk of phosphate stone formation. Urology. 2016;98:39–43. doi:10.1016/j.urology.2016.08.007
- 14.↑
Funaba M, Yamate T, Narukawa Y, et al. Effect of supplementation of dry cat food with d,L-methionine and ammonium chloride on struvite activity product and sediment in urine. J Vet Med Sci. 2001;63(3):337–339. doi:10.1292/jvms.63.337
- 15.↑
Denhart JW. Efficacy and toxicity if D, L methionine and methionine hydroxy analogue as a urinary acidifier in cats. Dissertation. Iowa State University; 1990.
- 16.↑
Grissett G, Fleming S, Neizman K. Evaluation of orally supplemented D,L methionine as a urine acidifier for small ruminants. J Vet Intern Med. 2012;26:760.
- 17.↑
Jones ML, Streeter RN, Goad CL. Use of dietary cation anion difference for control of urolithiasis risk factors in goats. Am J Vet Re. 2009;70(1):149–155. doi:10.2460/ajvr.70.1.149
- 18.↑
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–191. doi:10.3758/BF03193146
- 19.↑
Plumb DC. Ammonium chloride. Plumb’s veterinary drugs. 2023. Accessed December 12, 2023. https://app.plumbs.com/drug/A60Nyek6GjPROD?source
- 20.↑
Belknap EB, Pugh DG. Diseases of the urinary system. In: Pugh DG, ed. Sheep and Goat Medicine. Saunders; 2002:255–276.
- 21.↑
Sprake P, Roussel AJ, Steward R, Bissett WT. Abstract FA-7: the effect of ammonium chloride treatment as a long term preventative approach for urolithiasis in goats and a comparison of continuous and pulse dosing regimes. J Vet Int Med. 2012;26(3):760.
- 22.↑
Jacobs D, Heimbach D, Hesse A. Chemolysis of struvite stones by acidification of artificial urine–an in vitro study. Scand J Urol Nephrol. 2001;35(5):345–349.
- 23.↑
Goff JP. Calcium and magnesium disorders. Vet Clin North Am Food Anim Pract. 2014;30(2):359–381. doi:10.1016/j.cvfa.2014.04.003
- 24.↑
Charbonneau E, Pellerin D, Oetzel GR. Impact of lowering dietary cation-anion difference in nonlactating dairy cows: a meta-analysis. J Dairy Sci. 2006;89(2):537–548. doi:10.3168/jds.S0022-0302(06)72116-6
- 25.↑
Freitag JRB, Wilkens MR, Muscher-Banse AS, et al. Effects of diets differing in dietary cation-anion difference and calcium concentration on calcium homeostasis in neutered male sheep. J Dairy Sci. 2021;104(11):11537–11552. doi:10.3168/jds.2021-20334
- 26.↑
Overton TR, Waldron MR. Nutritional management of transition dairy cows: strategies to optimize metabolic health. J Dairy Sci. 2004;87:E105–E119. doi:10.3168/jds.S0022-0302(04)70066-1
- 27.↑
Bartges JW, Kirk C, Lane IF. Update: management of calcium oxalate uroliths in dogs and cats. Vet Clin North Am Small Anim Pract. 2004;34(4):969–987. doi:10.1016/j.cvsm.2004.03.011
- 28.↑
Alexander RT, Cordat E, Chambrey R, Dimke H, Eladari D. Acidosis and urinary calcium excretion: insights from genetic disorders. J Am Soc Nephrol. 2016;27(12):3511–3520. doi:10.1681/ASN.2016030305
