Decrease In Urinary pH Research Articles

Daily and Weekly Urine Variations in Bacterial Growth Susceptibility in Postmenopausal Women With no History of Urinary Tract Infection: A Pilot Study

ObjectivesTo evaluate bacterial growth in the bladder as a major virulence factor during urinary tract infections (UTIs), we assessed the variability of uropathogenic bacterial growth in urine samples over multiple timepoints from three postmenopausal women with no history of UTI. MethodsFollowing IRB approval, postmenopausal women who never had a UTI provided mid-stream urine samples three times daily (8 a.m., 12 p.m. and 4 p.m.), twice a week over two weeks, as well as dietary intake logs. Each sample was studied for pH and bacterial growth using three uropathogenic Escherichia coli (E.coli) strains (LRPF007, KE40, UTI89), one uropathogenic Enterococcus faecalis strain (HRH40), and one non-pathogenic E. coli strain (W3110). ResultsSimilar mean growth yields were observed for the uropathogenic strains (mean ∆OD600 = 0.1 – 0.13) with high variability (standard deviation (SD) = 0.13 – 0.28) and lower mean growth for the non-pathogenic strain (mean ∆OD600 = 0.05). Urine from each individual at different collection times never had the same bacterial growth potential for any bacterial strain. There were significant associations between urine pH decrease with higher fat (p=0.017), vitamin D (p=0.02), magnesium (p=0.049), fluid (p=0.013), and ash (p=0.01) intake. ConclusionsMajor variations were observed in the bacterial growth response in the urine of the same individuals. These variations imply a requirement for a normalization procedure, e.g., growth in synthetic urine, for analysis of bacterial growth in urine. There were significant associations between decreased urine pH and several nutrients found in foods that are classified as highly acidic.

Urine pH as predictor of blood acid-base status in dairy cattle fed acidogenic diets

We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field conditions in cows fed acidogenic diets. Eighty-six cows were sampled for urine and blood. Urine pH was evaluated immediately after collection, and blood acid-base status was evaluated within 2 hours of collection using a portable blood analyzer. Twenty-five cows were classified as having severe metabolic acidosis (blood pH ≤ 7.4; bicarbonate < 24 mmol/L, base excess ≤ −0.5; PCO2 low to normal concentrations and urine pH between 4.88 and 5.71. There was a positive linear association between urine pH and blood pH (r = 0.46), and between urine pH and base excess (r = 0.74). The area under the ROC curve was 0.91 (CI 95 %= 0.84–0.96; good-excellent test). The optimal cut-off value for urine pH to categorize a cow with severe metabolic acidosis was 5.5 (94 % specificity and 72 % sensitivity). For each 0.1 unit of decrease in urine pH below 5.5, cows were 1.6 times (95 % CI= 1.3–2.1) more likely to exhibit a severe metabolic acidosis. We conclude that a urine pH of 5.5 or less is indicative of more life-threatening metabolic acidosis in dairy cows.

Modern aspects of comorbidity of urological disease and metabolic syndrome

Urinary stone disease (USD) is one of the most common urological diseases occurring mainly in people of working age. USD is associated with metabolic disorders, the causes of which include endogenous and exogenous factors. Metabolic syndrome (MS) is a “non-infectious epidemic” that manifests itself in diabetes, hypertension, atherosclerosis, and obesity. The bidirectionality of metabolic processes is an important factor of USD and MS. Aim. The paper aims at reviewing modern literary sources regarding the determination of pathogenetic links between the comorbidity of USD and MS. Results. Nephrolithiasis spreads and recurs simultaneously with obesity. A decrease in urine pH, which is the basis for the formation of urate stones, is associated with the presence of obesity, insulin resistance, and MS. Under such conditions, urine alkalinization is the main treatment for urolithiasis. The risk of stone formation increases when the body mass index is more than 30 kg/m2. Among patients with insulin resistance, nephrolithiasis is more severe, and kidney stones occur more often. The relationship between the hypertensive component of MS and USD has been established. Disorders of lipid metabolism have a negative prognosis, causing physicochemical aberrations in urine and the development of nephrolithiasis. Hyperuricemia is related to both the ability of insulin to reduce uric acid clearance in the proximal renal tubules and insulin resistance. The link between USD and chronic inflammation is based on an increase in the endogenous synthesis of oxalates from endogenous glycogenic amino acids, which leads to the development of hyperoxaluria in patients with MS. Clinical studies show the formation of kidney stones in conditions of oxidative stress, an association between stone formation and the development of MS, coronary heart disease, arterial hypertension, which is the result of common pathogenetic characteristics. Conclusions. The comorbidity of USD and MS is a systemic disorder. Kidney stone formation is associated with a decrease in urine pH against the background of MS. Hyperuricemia is comorbid with insulin resistance, dyslipoproteinemia, arterial hypertension, and abdominal obesity. Systemic chronic inflammation, comorbid with obesity and USD, based on an increase in the endogenous synthesis of oxalates from endogenous glycogenic amino acids. Oxidative stress has a common pathogenetic link between stone formation and insulin resistance, atherosclerosis, hypertension, and obesity.

The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice.

Previous studies implicated the histamine H4 receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H4 receptor knockout mice (H4R−/−). Healthy and diabetic H4R−/− mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H4R−/− and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H4R−/− mice displayed a higher basal glycemia. H4R−/− mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H4R−/− mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H4R−/− mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H4R−/− mice. The AQP1 and AQP7 patterns were also different between H4R−/− and wild-type diabetic mice. The collected results highlight the role of the histamine H4 receptor in the control of renal reabsorption processes, particularly albumin uptake.

Urinary tract infections in culled sows from Greek herds: prevalence and associations between findings of histopathology, bacteriology and urinalysis

BackgroundUrinary tract infections (UTI) of sows characterized by cystitis, which may progress to ureteritis and pyelonephritis, can affect their productivity, longevity and welfare. In this study, we determined the prevalence of UTI by histopathology and bacteriology. Furthermore, we investigated possible associations between histologically confirmed cystitis and the results of urinalysis and urine cultures in culled sows from three farrow-to-finish herds in Greece.Materials and methodsOne hundred eighty-five routinely culled sows were included in the study. Their urinary bladder was collected from abattoirs and subjected to histopathology. Furthermore, urinalysis and urine cultures were performed on urine samples aseptically collected from the bladders.ResultsHistologically confirmed cystitis was evident in 85/185 (45.94%) culled sows. Among those, 44 (51.76%) suffered from acute and 41 (48.24%) from chronic inflammation. The majority of positive urine cultures were due to colonization of the urinary tract with E.coli, which accounted for 55.81% of the total cases, followed by Staphylococcus spp. which accounted for 18.60% of detected infections. Evidence of cystitis was associated with bacteriuria and sows with bacteriuria were 2.30 (P = 0.03, 95% CI: 1.10–4.83) times more likely to have histologically confirmed cystitis compared to sows with negative urine cultures. Bacteriuria was associated with proteinuria (P < 0.01, OR = 9.72, 2.63–35.88), increased urine pH (P < 0.01, 3.40, 1.10–10.56) and presence of sediment (P < 0.01, 6.00, 1.50–23.76) in urine. Sows with proteinuria had 9.72 (P < 0.01, 2.63–35.88) times higher odds of bacteriuria than those without. Histologically defined cystitis was associated with proteinuria (P < 0.01, 2.03–13.20) and decreased urine pH (P < 0.01, 0.13–0.72). Sows with proteinuria were 5.18 (P < 0.01, 2.03–13.2) times more likely to have histological lesions consistent with cystitis, than those without. For one unit increase in pH, it was 3.20 (P = 0.006, 1.39–7.69) times less likely for a sow to have chronic or acute cystitis compared to absence of cystitis.ConclusionIn the studied population, UTI affected almost one out of two culled sows. Bacteriuria, which was more common among sows with UTI than those without, was mainly ascribed to members of the intestinal and environmental bacteria. Proteinuria and the existence of urine sediment which were associated with UTI, could be used as proxy traits for UTI in live sows.

Prospective Evaluation of Daily and Weekly Urine pH Variations Along With Diet Intake in Postmenopausal Women With Recurrent Urinary Tract Infections.

Acidic urine pH may be protective against recurrent urinary tract infections (RUTIs). After reviewing the literature, we primarily analyzed urine pH fluctuations and secondarily compared them with diet in older women with RUTIs. After IRB approval, postmenopausal women with documented RUTIs were enrolled. Participants were given preformatted charts to record urinalysis reagent strips (Medimpex) findings 4 times per day and concomitant food/beverage intake (food diary). Urine cultures at baseline ensured no infection during measurement period. Nutrient content reported in food diaries was analyzed by an experienced registered dietitian and compared with parallel fluctuations in urine pH. Of 26 women with median age of 72 years (55-86 years), the first 3 days of diet and urine pH recordings found that 17 (65%) of 26 exhibited urine pH variation greater than 1 unit, with an overall median of 6 (5-9). Comparing dietary analysis and urine pH changes, beta-carotene (P = 0.017) and total dietary sugar intake (P = 0.036) were associated with a decrease in urine pH, whereas monounsaturated fatty acids (MFA, 22:1, P = 0.023) and protein (P = 0.028) were associated with an increase in urine pH. In this real-life, observational study, 65% of older women with RUTIs exhibited notable changes in urine pH, with decreased urine pH associated with nutrients found in orange and yellow vegetables and several major food groups. A longitudinal study is needed to determine if changing an individual's diet and/or adding supplements could decrease the urine pH, thus affecting the rate of RUTIs.

Reduction of ureteral stent encrustation by modulating the urine pH and inhibiting the crystal film with a new oral composition: a multicenter, placebo controlled, double blind, randomized clinical trial

BackgroundEncrustation of ureteral double J stents is a common complication that may affect its removal. The aim of the proposed study is to evaluate the efficacy and safety of a new oral composition to prevent double J stent encrustation in indwelling times up to 8 weeks.MethodsA double-blinded, multicenter, placebo-controlled trial was conducted with 105 patients with indwelling double J stents enrolled across 9 public hospitals in Spain. The patients were randomly assigned (1:1) into intervention (53 patients) or placebo (52 patients) groups for 3 to 8 weeks and both groups self-monitored daily their morning urine pH levels. The primary outcome of analysis was the degree of stent ends encrustation, defined by a 4-point score (0 – none; 3 – global encrustation) using macroscopic and electron microscopy analysis of crystals, after 3 to 8-w indwelling period. Score was exponentially transformed according to calcium levels. Secondary endpoints included urine pH decrease, stent removal, and incidence of adverse events.ResultsThe intervention group benefits from a lower global encrustation rate of stent ends than placebo group (1% vs 8.2%; p < 0.018). Mean encrustation score was 85.12 (274.5) in the placebo group and 18.91 (102.27) in the intervention group (p < 0.025). Considering the secondary end points, treated patients reported greater urine pH decreases (p = 0.002). No differences in the incidence of adverse events were identified between the groups.ConclusionsOur data suggest that the use of this new oral composition is beneficial in the context of ureteral double J indwelling by decreasing mean, as well as global encrustation.Trial registrationThis trial was registered at www.clinicaltrials.gov under the name “Combined Use of a Medical Device and a Dietary Complement in Patient Urinary pH Control in Patients With an Implanted Double J Stent” with date 2nd November 2017, code NCT03343275, and URL.

PECULIARITIES OF UNITIOL INFLUENCE ON THE KIDNEY FUNCTIONING IN RATS OF THE JUVENILE AGE

This investigation shows an influence of different dosages of unitiol (sodium2,3-dimercaptopropanesulfonate) on the kidney functioning in juvenile rats.Purpose of the work is to study unitiol influence upon the kidney excretion function insexually mature rats at single and repeated injections.Material and methods. This investigation was performed on the juvenile male rats withthe body weight 95.0±8.5 g. The kidney functioning was determined for the single andrepeated (10, 20 and 30 days) injections of 5 % unitiol solution (50 mg/kg, subcutaneously)against a background of the additional water load realized through introduction of warmwater into the stomach in the volume of 5 % of the animal’s body weight. The concentrationOriginal research53Клінічна та експериментальна патологія. 2020. Т.19, №1(71) ISSN 1727-4338 https://www.bsmu.edu.uaof sodium, potassium ions, creatinine, proteins, ammonium, titratable acids and pH weredetermined in the rat’s urine and then compared with the corresponding values obtainedfrom the control and previous groups under study.Results. No significant changes were determined in the excretion and acid-regulationfunctions of the rat’s kidney in 2.5 hours after unitiol single injection against a backgroundof the water load. However, the concentration of sodium increased 1.7 times as large andthe concentration of potassium decreased correspondingly. No changes were registeredin diuresis while excretion of sodium increased 1.9 times as large, kaliuresis decreased1.6 times, sodium/potassium urine coefficient increased 2.6 times.After daily untiol injection during 10 days, concentration of sodium in the urine became3.2 times less in comparison with animal’s reaction to the single injection of the drugand 1.9 times less than that in the control group. Against a background of the 20 and30 days of the drug injection, the concentration of sodium has decreased almost thricecomparing to the control group value. Natriuresis decreased by 4 times comparing tothe value achieved after a single drug injection, decreased twice in comparison withthe control group and then it remained unchanged throughout the following 20- or 30-days long injections. No significant deviations from the control value were found in thepotassium concentration after the repeated injections of the drug. Kaliuresis decreasedafter the single injection but then it increased to its control value following the injection ofthe drug during 20 days. The urine sodium/potassium coefficient decreased 1.7-2.5 timescomparing to the control value after the repeated injections. No significant changes wereregistered throughout the entire experiment in the endogenous creatinine excretion andconcentration. The protein concentration decreased by 2.2 times comparing to its controllevel after unitiol application during 10 days and then it remained unchanged after 20-or 30-days long courses of injections. The indices of titratable acids and ammoniumexcretion became in 1.8 times less than those in the control group, then they increasedafter the 20th day and on the 30th day of injection they didn’t significantly differ fromthe control indices. The hydrogen excretion increased 2.4 and 2.8 times as large after20 and 30 days of the drug injection respectively at urine pH decrease. Unlike the singleinjection, the repeated unitiol injections significantly decrease natriuresis and the proteinexcretion with urine. Some age-related features of unitiol influence on the kidneys can beaccounted at different types of its administration as a chemical antidote.Conclusions. 1. Unitiol influence on the kidney functioning combined with the water loadin juvenile rats depends on the duration of application.2. The natriuretic effect increases and the kaliuretic effect decreases after a singleinjection of the drug when there is no significant influence on diuresis, excretion andacid-regulating parameters of the kidney. 3. A prolonged (10, 20, 30 days) application ofunitiol causes some intensification of sodium-retaining and hypoproteinuretic activitiescombined with some increase in the urine pH.

Prevalence of latent acidotic stress in dairy cows in the Şanliurfa region

This study aimed to determine the incidence of latent acidotic stress (LAS), which is an important problem in dairy cow breeding in Turkey, to investigate net acid-base excretion in urine, and to provide veterinary doctors with information about the early diagnosis and treatment of LAS. Two study groups were formed according to the rumen fluid pH values: LAS group (19 cows) with 5.2 &lt; pH &lt; 6.0 (19 cows) and healthy group (81 cows) with 6.0 &lt; pH &lt; 7.2. Blood, urine and ruminal fluid samples were taken after a general clinical examination of the animals. The physical properties of the rumen fluid, methylene blue reduction time, total infusoria number, and volatile fatty acid (VFA) amounts were determined. In addition, examinations of blood gases, urine pH, and net acid-base excretion (NABE) were performed. The general physical examination did not reaveal any statistically significant difference in the body temperature between the LAS group (n = 19) and the control group (n = 81) (p = 0.614), but a significant increase in the heartbeat, respiratory frequency, and the number of rumen movements was observed in the LAS group (p = 0.001). The following findings were observed in the rumen fluid from cows of the LAS group: decreased methylene blue reduction time (p = 0.001), decreased pH (p = 0.001) and infusoria density (p = 0.001), increased sedimentation time (p = 0.001) and total VFA amount (p = 0.001), no flotation. Compared with the healthy cows, the LAS group showed decreased blood pH (p = 0.001) and oxygen pressure (pO2) (p = 0.001), increased carbon dioxide pressure (pCO2), base excess (BE) and bicarbonate (HCO3) values (p = 0.001), and decreased urine pH (p = 0.001) and net acid-base excretion (p = 0.001) values. The incidence of latent acidotic stress in dairy cows in the Sanliurfa region was determined as 19%. In addition, it was concluded that net acid-base excretion values in urine can be used as an auxiliary parameter in the diagnosis of LAS and can be easily applied in the field.

Tubular Acidification Defect in Adults with Sickle Cell Disease.

Metabolic acidosis is a frequent manifestation of sickle cell disease but the mechanisms and determinants of this disorder are unknown. Our aim was to characterize urinary acidification capacity in adults with sickle cell disease and to identify potential factors associated with decreased capacity to acidify urine. Among 25 adults with sickle cell disease and an eGFR of ≥60 ml/min per 1.73 m2 from a single center in France, we performed an acute acidification test after simultaneous administration of furosemide and fludrocortisone. A normal response was defined as a decrease in urinary pH <5.3 and an increase in urinary ammonium excretion ≥33 µEq/min at one or more of the six time points after furosemide and fludrocortisone administration. Of the participants (median [interquartile range] age of 36 [24-43] years old, 17 women), 12 had a normal and 13 had an abnormal response to the test. Among these 13 participants, nine had normal baseline plasma bicarbonate concentration. Plasma aldosterone was within the normal range for all 13 participants with an abnormal response, making the diagnosis of type 4 tubular acidosis unlikely. The participants with an abnormal response to the test were significantly older, more frequently treated with oral bicarbonate, had a higher plasma uric acid concentration, higher hemolysis activity, lower eGFR, lower baseline plasma bicarbonate concentration, higher urine pH, lower urine ammonium ion excretion, and lower fasting urine osmolality than those with a normal response. Considering both groups, the maximum urinary ammonium ion excretion was positively correlated with fasting urine osmolality (r2=0.34, P=0.002), suggesting that participants with sickle cell disease and lower urine concentration capacity have lower urine acidification capacity. Among adults with sickle cell disease, impaired urinary acidification capacity attributable to distal tubular dysfunction is common and associated with the severity of hyposthenuria. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_12_10_CJN07830719.mp3.

Increased body fatness adversely relates to 24-hour urine pH during childhood and adolescence: evidence of an adipo-renal axis

Reduced net acid excretion (NAE) capacity indicates a decrease in renal function. This reduction manifests as a disproportionally low 24-h urine pH in relation to the sum of actually excreted ammonium and titratable acidity by the kidney. The aim of this study was to test the hypothesis that higher body fatness is one determinant of kidney function impairment with a lowered urine pH even at a young age. NAE, pH, urea, and creatinine were measured in 24-h urine samples from 524 healthy children and adolescents (aged 6-17 y) participating in the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. Body fatness was assessed anthropometrically by body mass index-standard deviation score (BMI-SDS), fat mass index (FMI), body fat % (BF%), and waist circumference (WC). Multivariable linear and mixed linear regressions were used to examine cross-sectionally (n=524 urine samples; age groups: 6-8, 9-11, 12-14, 15-17 y) and longitudinally (n=1999 urine samples) the associations of body fatness with 24-h urine pH as the outcome variable, respectively. After adjusting for the kidneys' total net acid load (24-h urinary NAE) and further relevant covariates, FMI showed significant inverse relations with urinary pH in all 4 age groups, and BMI-SDS, BF%, and WC each in 3 out of these 4 groups (P≤0.02). Longitudinal results substantiated these interindividual relations and further showed intraindividual increases in body fatness to be paralleled by urine pH decreases (P≤0.0002). Independent of underlying acid load, an early increase in body fatness is associated with increased free proton excretion, and thus with a decline in the kidney's acid excretion function, which could potentiate the risk of renal nephrolithiasis.

Risk Factors and Mechanisms Underlying Cross-Shift Decline in Kidney Function in Guatemalan Sugarcane Workers.

Identify early biomarkers and mechanisms of acute kidney injury in workers at risk of developing chronic kidney disease of unknown origin (CKDu). We assessed cross-shift changes in kidney function and biomarkers of injury in 105 healthy sugarcane workers. We obtained pre-harvest clinical data as well as daily environmental, clinical, and productivity data for each worker. The average percent decline in cross-shift estimated glomerular filtration rate (eGFR) was 21.8% (standard deviation [SD] 13.6%). Increasing wet bulb globe temperature (WBGT), high uric acid, decreased urine pH, urinary leukocyte esterase, and serum hyperosmolality were risk factors for decline in kidney function. Sugarcane workers with normal kidney function experience recurrent subclinical kidney injury, associated with elevations in biomarkers of injury that suggest exposure to high temperatures and extreme physical demands.

Furosemide reduces BK-αβ4-mediated K+ secretion in mice on an alkaline high-K+ diet.

Special high-K diets have cardioprotective effects and are often warranted in conjunction with diuretics such as furosemide for treating hypertension. However, it is not understood how a high-K diet (HK) influences the actions of diuretics on renal K+ handling. Furosemide acidifies the urine by increasing acid secretion via the Na+-H+ exchanger 3 (NHE3) in TAL and vacuolar H+-ATPase (V-ATPase) in the distal nephron. We previously found that an alkaline urine is required for large conductance Ca2+-activated K+ (BK)-αβ4-mediated K+ secretion in mice on HK. We therefore hypothesized that furosemide could reduce BK-αβ4-mediated K+ secretion by acidifying the urine. Treating with furosemide (drinking water) for 11 days led to decreased urine pH in both wild-type (WT) and BK-β4-knockout mice (BK-β4-KO) with increased V-ATPase expression and elevated plasma aldosterone levels. However, furosemide decreased renal K+ clearance and elevated plasma [K+] in WT but not BK-β4-KO. Western blotting and immunofluorescence staining showed that furosemide treatment decreased cortical expression of BK-β4 and reduced apical localization of BK-α in connecting tubules. Addition of the carbonic anhydrase inhibitor, acetazolamide, to furosemide water restored urine pH along with renal K+ clearance and plasma [K+] to control levels. Acetazolamide plus furosemide also restored the cortical expression of BK-β4 and BK-α in connecting tubules. These results indicate that in mice adapted to HK, furosemide reduces BK-αβ4-mediated K+ secretion by acidifying the urine.

Effect of treatment with oral Ca boluses following calving on concentrations of Ca in serum in pasture-based dairy cows

AIMSTo assess the effect of the administration of two oral Ca boluses on concentrations of total Ca, β-hydoxybutyrate (BHB) and non-esterified fatty acids (NEFA) in serum, and urine pH, in recently calved pasture-fed dairy cows.METHODSFriesian or Friesian cross Jersey cows from one dairy farm were blocked by age and randomly assigned to no treatment (control; n=14), or treatment (n=13) with two oral Ca boluses administered approximately 12 hours apart, with the first bolus being given within 14 hours of calving. Each bolus weighed 198 g and contained 43 g of Ca; 31 g of Ca from calcium chloride and 12 g of Ca from calcium sulfate. Cows were enrolled over three calendar days, and all cows were managed in one group during the 24-hour study period. Blood samples were collected at 0, 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 hours after the initial treatment. Serum from each time point was analysed for concentrations of total Ca, and from 0, 12, and 24 hours for NEFA and BHB. Urine was collected at 0, 12 and 24 hours for pH measurement and pH was categorised as <7 or ≥7. The effect of treatment on percentage change in concentrations of Ca in serum relative to 0 hours, and concentrations of NEFA, BHB and urine pH, was examined using multivariable repeated measures mixed models with cow as a random effect.RESULTSIn the final multivariable model for percentage change in concentrations of Ca, there was an interaction between time and treatment (p=0.004), with the percentage increase being higher in treatment than control cows at 1, 2, 4, 8 and 13 hours. At 12 hours, 5/13 (41%) treated cows had a urine pH <7compared to 0/12 (0%) control cows (p<0.001), and at 24 hours 13/13 (100%) treated cows had urine pH <7 compared to 0/12 (0%) control cows (p<0.001). Over the 24-hour period, mean concentrations of NEFA or BHB in serum were similar in treated and control cows (p>0.3).CONCLUSIONS AND CLINICAL RELEVANCEOral treatment with two Ca boluses increased concentrations of total Ca in serum and decreased urine pH in pasture-fed cows. This bolus has the potential to reduce the prevalence and duration of subclinical hypocalcaemia in recently calved cows.

Novel role(s) for Nonmuscle Myosin 2 isoforms Myh9 and Myh10 in renal epithelial cells and tubular disease.

Nonmuscle Myosin 2 (NM2) is an actin associated motor protein that is essential for cellular processes like adhesion, migration, polarity, and division. The NM2 family is composed of three isoforms, NM2A, NM2B, and NM2C encoded by genes Myh9, Myh10 and Myh14 respectively. Each of these isoforms have both unique and redundant functions due to differences in their affinities for actin and ATPase activities. Our previous work demonstrated a novel role for Myh9&amp;10 in both compensatory and constitutive clathrin mediated endocytosis. Previous studies have shown that point mutations in the NM2A gene, MYH9, are associated with human disease involving blood, eye, ear and kidney disorders. We hypothesized that the underlying mechanism in MYH9 related kidney disorders is compromised renal epithelial endocytosis and transport. Consistent with the hypothesis all three NM2 isoforms have unique membrane associated expression and localization pattern along the nephron and collecting duct segments. While, Myh9 expression was limited to the apical membrane of the TAL segment of the loop of Henle, Myh10 and Myh14 isoforms had much broader expression pattern along the tubular segments. All isoforms shared distinct localization to the apical and/or basolateral membranes along the renal tubules and presented a micro‐domain like pattern in some tubular segments. Interestingly, in the collecting duct segment, Myh10 and Myh14 are uniquely expressed in principal and intercalated cells, respectively. The distinct localization of the NM2 isoforms within the epithelial cells of the renal tubules suggests that each isoform has a unique function and loss of each isoform may lead to specific pathophysiology. Inducible conditional genetic inactivation (cKO) of Myh9, Myh10, and both Myh9&amp;10 within the renal tubules of adult mice using the doxycycline inducible Pax8‐&gt;rtTA; Tet‐O‐Cre system revealed critical roles of Myh9 and Myh10 in the renal tubular segments. Histological evaluation showed that Myh9 cKO mice had mild tubular dilation by 12 weeks of age with infiltrating cells that progressed to tubulointerstitial disease over time. The Myh9&amp;10 cKO mice show decreased urine pH and increased blood urea nitrogen and serum creatinine levels by 9 weeks of age. Histological analysis revealed tubular dilation, cellular infiltration, inflammation as well as glomerular defects by 12 weeks of age and mice were moribund by 4 – 5 months of age. Preliminary results indicate loss of GPI‐anchored protein, Uromodulin from the apical membrane of the TAL tubules in Myh9 and Myh9&amp;10 cKO mice. We are beginning to characterize the localization pattern of membrane‐associated channels (ROMK) and co‐transporters (NKCC2) in these mouse models and our results indicate changes in their localization pattern along the tubular segments. Our mouse models demonstrate a novel and critical role for NM2 isoforms in maintaining renal tubular function in the adult mouse kidney. We envision that NM2 isoforms participate in anchoring, targeting, and/or transport of membrane associated proteins in the tubular epithelial cells and loss of function of NM2 isoforms results in progressive tubular disease.Support or Funding InformationFunding for this project and the Core facilities at Sanford Research are through NIH COBRE grants (P20GM103620 and P20GM103548) as well as Sanford Research program funds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Association of Low Urine pH with Insulin Resistance in Non-Diabetic Japanese Subjects.

Epidemiology studies have revealed that patients with obesity, hyperglycemia, or hypertension are associated with a decreased urine pH. These metabolic disorders are related to insulin resistance; however, the association between urine pH and insulin resistance remains unclear. To evaluate this association while controlling for covariates, the present study was conducted in 1084 non-diabetic Japanese subjects undergoing health examination. Fasting urine pH was analyzed using an automated urine dipstick analyzer. The subjects were divided into five groups according to urine pH: those with pH <5.5, 5.5, 6.0, 6.5, and >6.5. Insulin resistance was determined using the homeostatic model assessment of insulin resistance (HOMA-IR) and divided into three categories: lower, middle, and higher tertiles of HOMA-IR. Analysis of covariance and multivariate logistic regression analysis were used to control confounding factors including serum uric acid. Analysis of covariance showed an increase in the mean HOMA-IR from 1.26, 1.46, 1.69, and 1.75 to 1.89 with a decrease in urine pH (p<0.001). Subjects with urine pH ≤5.5 had a significantly higher HOMA-IR than those with urine pH>6.5. Furthermore, multivariate logistic regression analysis showed that urine pH had an inverse and independent association with HOMA-IR. In subjects with urine pH 5.5 and <5.5, adjusted odds ratio (95% confidence interval) for the incidence of higher tertile of HOMA-IR was 1.34 (1.04-1.73) and 1.52 (1.09-2.13), respectively (reference, subjects with a urine pH>6.5). Insulin resistance is independently associated with a lower urine pH, possibly via lower formation of ammonium in the kidneys.

Renal Evaluation in Common Variable Immunodeficiency.

Introduction Common variable immunodeficiency (CVID) comprises a heterogeneous group of disorders characterized by impaired antibody production. Kidney involvement in CVID is described in isolated and sporadic case reports. The objective of this study was to study the renal function pattern in CVID patients through glomerular and tubular function tests. Methods Study of 12 patients with CVID diagnosis and 12 healthy control individuals. Glomerular filtration rate (GFR), fractional excretion of sodium (FENa+) and potassium (FEK+), urinary concentration, and acidification capacity were measured. In addition, microalbuminuria and urinary monocyte chemoattractant protein-1 (MCP-1) were evaluated as markers of selectivity of the glomerular barrier and inflammation, respectively. Results In relation to glomerular markers, all CVID patients had normal GFR (>90 mL/min/1.73 m2), and microalbuminuria and urinary MCP-1 levels were also similar to those of controls. Interestingly, CVID patients had reduced urinary concentration capacity, as demonstrated by lower U/POsm ratio, when compared to controls. Also, while all control subjects achieved a urinary pH less than 5.3, no CVID patients showed a decrease in urinary pH to such levels in response to acid loading with CaCl2, characterizing impaired urinary acidification capacity. Conclusion Patients showed a trend towards an elevated prevalence of tubular dysfunction, mainly related to urinary acidification and concentration capacities.

Is it safe to prescribe ascorbic acid for urinary acidification in stone-forming patients with alkaline urine?

To study the effect of ascorbic acid (AA) supplementation on urinary pH, metabolic stone workup parameters, and development of de novo urolithiasis in stone-forming patients. A retrospective review of the patients followed-up at a tertiary stone centre between September 2009 and October 2015 was performed. Patients with recurrent urolithiasis who received AA supplementation as a urinary acidifying agent were included in the study. Detailed metabolic stone work-up, including two 24-hour urine collections obtained pre- and post-AA supplementation were compared. In addition, imaging studies were reviewed to assess the development of de novo urolithiasis. Twenty-four patients were included in the study with a mean age of 60.6 years and a median daily AA dose of 1000 mg (range: 500-2000 mg). Median follow-up period was 22.6 months (range: 19.7-32.1). After AA supplementation, there was a significant decrease in urinary pH (7.6 vs. 6.9, p=0.02). Although there was no significant increase in the daily oxalate excretion, two patients (8.3%) had their AA dose reduced or discontinued due to de novo hyperoxaluria (342.9 vs 510.2 umol/day; p=0.75). Other serum and urinary parameters did not show any significant changes. Eight (33.3%) patients developed de novo urolithiasis with struvite and carbonate apatite being the major components. AA supplementation resulted in significantly lower urinary pH in patients with recurrent urolithiasis and alkaline urine pH. Prospective studies are needed to assess whether this reduction in urinary pH is associated with lower stone recurrence rates.

Signification of distal urinary acidification defects in hypocitraturic patients.

Background and objectivesHypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia.Materials and methodsThis retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 μmol/min and defined idiopathic hypocitraturia.ResultsEleven patients (16.4%) had low HCO3- and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24–0.47] vs. 0.22 [0.08–0.37] mmol/mmol creatinine (P = 0.04).ConclusionsPatients with hypocitraturia and normal plasma HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention.

The influence of oxazaphosphorine agents on kidney function in rats

Background and objectiveThe application of cytostatic oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide (IF) is associated with the risk of kidney damage that, depending on the type of drug, dose and route of administration, adopts a different clinical entity and severity. The aim of our study was to assess the influence of CP and IF on the kidney histology and function in rats intraperitoneally treated with four doses of either CP or IF. Materials and methodsA total of 30 rats were divided into three groups (10 in each group): group 1 (control), sham treated with saline solution, group 2 (treated with 75mg/kg b.w. of CP), and group 3 (treated with 60mg/kg b.w. of IF). After the treatment rats were sacrificed, blood was collected and nephrectomy and cystectomy were performed. Qualitative and quantitative parameters (including neutrophil gelatinase-associated lipocalin-1, NGAL-1) of kidney function were assayed in urine and plasma. ResultsCP-treated rats were characterized by a significant polyuria, decreased urine pH and by decreased daily urinary excretion of sodium, potassium, urea and uric acid accompanied by increased NGAL-1 excretion. A significant decrease of the plasma uric acid concentration was also observed. IF-treated animals were also characterized by decreased urine pH but with normal daily urinary excretion of assessed substances (except for reduced uric acid excretion).Both CP and IF treated rats did not show any histopathological abnormalities in their kidneys. ConclusionsCP caused more advanced kidney dysfunction and some indices suggested the development of prerenal acute kidney injury. In the CP-treated group some particularly marked urinary and plasma uric acid disturbances suggested compensation of increased oxidative stress as uric acid is considered to exert also antioxidant properties.