Urine pH Research Articles

EVALUATION AND COMPARISON OF DIAGNOSTIC EFFICACY OF INDICATORS TO SCREENING FOR PRIMARY ALDOSTERONISM BEFORE ENDOCRINE PATHWAY

Objective: To evaluate and compare the effectiveness to screen for primary aldosteronism (PA) before the endocrine performing among hypokalemia, the serum sodium to urinary sodium to (serum potassium) to urinary potassium (SUSPPUP) index, combination of urine pH, sex, and serum potassium (PFK score) and PA-nomogram prediction model.2 Design and method: From January 2010 to January 2014, 937 patients with hypertension were admitted in the People's Hospital of Xinjiang Uygur Autonomous Region. Fasting elbow venous blood was collected on admission day, serum, potassium, sodium and calcium ion levels were determined, calcium and phosphorus products were calculated, plasma sitting aldosterone/renin activity (ARR) were measured, and calculated. 24 h urine was collected and the ion level was measured. The pH value of urine was detected by pH test paper in the morning. Serum potassium (<3.5 mmol/L), SUSPPUP (>5.3/ (mmol/L)), PFK score (>2 points), nomogram prediction model (>21%) as positive screening criteria, ARR (>20ng/dL/ ng/mL/h) as positive endocrine screening index, were respectively used to predict and screen PA. The patients with positive ARR were confirmed PA using saline infusion test. The ROC curve was drawn to evaluate the efficacy of serum potassium, SUSPPUP, PFK score, and PA-nomogram prediction model to screen PA. Kappa test was used to evaluate its consistency with ARR screening results. Results: The area under ROC curve of serum potassium <3.5 mmol/L, SUSPPUP >5.3 (mmol/L)-1, PFK score >2 points, nomogram prediction probability>21% to screen PA in patients with hypertensive respectively were 0.61(95%CI:0.56∼0.66, P<0.001), 0.52(0.47∼0.57, P=0.479), 0.57(0.52∼0.62, P=0.005), 0.62(0.57∼0.67, P<0.001), and the sensitivity was 36%, 7%, 24% and 53%, the specificity was 86%, 96%, 90% and 70%, respectively. There was good consistency between nomogram prediction model or PFK score and ARR (Kappa=0.122, P <0.001, Kappa=0.092,P <0.001), and the Kappa value of nomogram prediction model with ARR was higher than the PFK score with ARR (X2=163.577, P < 0.001). Conclusions: The nomogram prediction model, which includes gender, serum potassium, calcium-phosphorus product and urine pH value, is more sensitive to screen PA in patients with hypertension, and the nomogram prediction probability>21% is more consistent with ARR.

Lithium-Induced Disruption of Intracellular Ca2+ Balance in the Collecting Duct Intercalated Cells Contributes to Metabolic Acidosis in Mice

INTRODUCTION. Lithium (Li+) is an effective mood stabilizer that continues to be widely used in modern psychiatric practice. One of the most common adverse effects of Li+ therapy is nephrogenic diabetes insipidus manifesting in reduced urinary concentrating ability due to impaired vasopressin (AVP) signaling in the collecting duct principal cells. While distal tubular acidosis has also been reported in patients receiving Li+, molecular determinants underlying the pathophysiological effects of Li+ on the collecting duct intercalated cells and renal acid-base transport remain to be fully elucidated. Activation of Gq-coupled vasopressin 1a receptors (V1aR) in A-intercalated cells reportedly induces intracellular Ca2+ ([Ca2+]i) mobilization and stimulates luminal H+ secretion, resulting in urine acidification. OBJECTIVE. The objective of this study was to test if Li+ impaired V1aR-induced [Ca2+]i response in the intercalated cells of murine collecting ducts. HYPOTHESIS. We hypothesized that Li+ markedly impaired V1aR-dependent [Ca2+]i signaling in A-intercalated cells causing the reduction of luminal proton secretion in the collecting duct. METHODS. We combined immunofluorescent imaging in freshly isolated collecting duct segments with metabolic cage studies in C57BL/6NJ (Jackson Labotatory) mice receiving a regular Teklad 2918 chow (control) or a Teklad 2918-based diet containing 0.3% lithium carbonate (Li+-treated) to evaluate how Li+ affects V1aR-mediated [Ca2+]i signal, H+ transport by intercalated cells, as well as urinary pH and ammonia excretion. RESULTS. We found that AVP elicited a transient [Ca2+]i response in the aquaporin-2 (AQP2) negative cells from collecting duct segments isolated from control mice. The response was mediated by Ca2+ release from the endoplasmic reticulum (ER), as it was inhibited by pretreatment of collecting duct segments with thapsigargin, a SERCA pump inhibitor. The amplitude of the AVP-induced calcium transient was 4 times lower in the AQP2-negative cells isolated from Li+-treated mice. Li+ intake remarkably facilitated store-operated calcium entry (SOCE) in the collecting duct cells, indicating chronic ER depletion and stress. At the systemic level Li+-treated mice exhibited urine alkalinization (by 0.8 pH units) and a 6-fold elevation in urinary ammonium excretion, when compared to controls. CONCLUSIONS. Intracellular Ca2+ signaling in the intercalated cells is an essential determinant of acid-base handling in the collecting duct. Our findings reveal that Li+ markedly alters [Ca2+]i signaling in the intercalated cells, causing urine alkalinization and elevated ammonium excretion, likely, to compensate for ensuing metabolic acidosis. NIDDK R01DK125464. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Regulation of renal acid-base balance by Epac isoforms in proximal tubule and collecting duct

Proper regulation of acid-base homeostasis has utmost significance for well-being and survival of the living organisms. Up to 50% of emergency room patients have notable disturbances in pH and associated morbific manifestations, which impedes effective treatment. Kidneys play a central role in regulation of acid-base balance by reabsorbing HCO3− via NHE-3 in the proximal tubule (PT) and secreting H+ via V-ATPase pump by the intercalated cells of collecting duct (CD). Exchange proteins directly activated by cAMP (Epac) are most prominently expressed in the proximal tubule and collecting ducts, the sites critical for acid-base transport in the renal tubule. However, the significance and physiological relevance of Epac isoforms (Epac1 and Epac2) for controlling HCO3− reabsorption and H+ secretion and by extension, the systemic pH regulation is not known. Here, we used transgenic mouse models lacking both or individual Epac1 and Epac2 isoforms to examine the systemic adaptation to acid-base insults and to inquire on the perturbed molecular signaling mechanisms and end-effectors in freshly isolated split-opened PTs and CDs using biochemical and fluorescent imaging tools. Deletion of Epac1&2 caused a dramatic decrease in NHE-3 protein levels in an additive manner. Moreover, we detected a marked redistribution of NHE-3 to the base of brush border in proximal tubule cells rendering its inactivation. Consistently, NHE-3 activity was more than 70% decreased upon Epac1&2 deletion, as was assessed by a rate of recovery after intracellular acidification in freshly isolated split-opened PTs. Furthermore, V-ATPase activity was similarly decreased in A-type of intercalated cells in freshly isolated CDs despite compensatory accumulation on the apical side, as monitored with confocal microscopy in cortical and medullary kidney sections of the knockout. In unstressed conditions, Epac1&2 deletion did not affect arterial pH and HCO3− levels, while urinary pH was significantly reduced. Dietary acid load (280 mM NH4Cl in drinking water for 3 days) unmasked severe hyperchloremic metabolic acidosis with pH 7.17±0.01 and HCO3− 14.5±0.6 mM and impaired urinary acidification. Deletion of Epac2 alone recapitulated the phenotype of double knockout, whereas Epac1−/− mice did not demonstrate notable deficiencies in response to dietary acid load. Overall, we concluded that Epac signaling plays a major role in urinary acidification with the dominant contribution of Epac2 isoform by regulating acid-base transport in both proximal tubule (via NHE-3) and the collecting duct (via V-ATPase). Epac1&2 and Epac2 deletion of impairs renal adaptation to the acid load resulting in severe metabolic acidosis. This research was supported by NIH-NIDDK DK117865, DK119170, AHA EIA35260097 (to O. Pochynyuk) and AHA-23POST1020372 (to K. Pyrshev). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Generation and characterization of collecting duct specific GPR56 knockout mice

GPR56 is a multifunctional adhesin G protein-coupled receptor involved in diverse biological processes, including neurodevelopment and disease, immune regulation, reproduction, hemostasis, and tumorigenesis. The role of GPR56 in the kidneys has been understudied. A recent study demonstrated that GPR56 in the glomerular endothelial cells promoted diabetic kidney disease progression via regulation of eNOS. Using RNAscope in situ hybridization (ISH) for GPR56 and aquaporin 2 (AQP2) followed by immunofluorescent labeling with NKCC2 (thick ascending limb, TAL marker), we detected GPR56 mRNA highly expressed in the collecting duct (both AQP2 positive principal cells and AQP2 negative intercalated cells) and TAL of the loop of Henle. In contrast, GPR56 mRNA is not detected in the proximal tubule or glomeruli. This expression pattern is further confirmed by quantitative RT-qPCR for GPR56 in microdissected inner medulla/inner stripe outer medulla and renal cortex. Of note, inner medulla/ inner stripe outer medulla is primarily composed of the collecting duct and the loop of Henle. GPR56 mRNA exhibited over a 6-fold higher expression levels in the inner medulla/inner stripe outer medulla compared to renal cortex, which is consistent with limited expression in the proximal tubule. To determine the physiological role of GPR56 in the collecting duct, we generated a collecting duct-specific GPR56 knockout (GPR56CD-KO) mouse model by crossing GPR56flox (Control, Con) with cadherin 16 Cre (Ksp-Cre) mice. The deletion of GPR56 in the collecting duct was confirmed by RNAscope ISH for GPR56 and AQP2 followed by fluorescent labeling with NKCC2. GPR56CD-KO mice were born at predicted Mendelian frequencies, appeared grossly indistinguishable from Con mice, and developed normally. For baseline phenotypic characterization, we found no differences in blood pH (7.21±0.01 vs 7.19±0.01, NS), blood HCO3− (17.4±0.5 vs 16.8±1.1 mmol/L, NS), blood Na+ (143±0 vs 144±0 mmol/L, NS), or blood K+ (4.3±0.1 vs 4.3±0.1 mmol/L, NS) between GPR56CD-KO (n=5, males) and Con mice (n=6, males). We also conducted metabolic cage experiments. No differences were observed for fluid intake (4.7±0.5 vs 4.5±0.2 mL/(day*30 g bodyweight), NS), urine volume (629±87 vs 662±108 mL/day, NS), urinary pH (5.75±0.03 vs 5.69±0.03, NS) or urine osmolality (2456±151 vs 2776±253 mOsm/kg, NS) between genotypes in baseline. After 24hr water deprivation, urine osmolality in both mice groups had significantly increased compared to that in baseline, however, no difference (Δ change: 558±82 vs 583±60 mOsm/kg, NS) was found between GPR56CD-KO and Con mice. In conclusion, we successfully generated collecting duct-specific GPR56 knockout mouse and found no defective urine concentrating ability in GPR56CD-KO mice. This mouse model will be useful to delineate the collecting duct-specific role of GPR56 for renal function, including acid-base regulation. We will also generate whole kidney GPR56 knockout mice to determine the isolated role of GPR56 in the loop of Henle compared to that in the collecting duct. This study is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (4R00DK127215). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparative evaluation of conventional and ultrasound assisted tube cystotomy for obstructive urolithiasis in cattle

The aim of this study was to evaluate the efficacy of conventional and ultrasound assisted tube cystotomy techniques for obstructive urolithiasis in 12 cattle by allowing two groups. Group-I, animals were subjected to conventional tube cystotomy, whereas in group- II, ultrasound assisted tube cystotomy was performed using Foley’s catheter under deep sedation with xylazine hydrochloride and local infiltration anaesthesia. Clinically, all animals showed urethral pulsation, dribbling of urine, futile attempts, bellowing, congested mucous membrane, sunken eyes, dry muzzle and teeth grinding. Non-significant changes were observed in haematological and biochemical values, however neutrophilia and alkaline pH of urine was prominent. Ultrasound assisted tube cystotomy technique consumed less time (40.00±1.29 min) with small incision and minimal bleeding as compared to conventional tube cystotomy.

The assembly factor Dmxl1 is required for H+(V)-ATPase assembly and function in mammals in vivo

The V-ATPase (proton pump) generates electrochemical gradients across cell membranes, driving essential biological processes. Critically, the two V-ATPase domains, V1 and VO, must assemble to produce a functional holoenzyme. V-ATPase dysfunction results in serious pathologies such as cancer, neurodegeneration, and diabetes, as well as systemic acidosis caused by reduced activity of proton-secreting intercalated cells (IC) in the kidney. However, very little is known about the molecular regulation of V-ATPase in mammals. We have identified a novel interactor of the IC-enriched B1 subunit of the mammalian V-ATPase, Drosophila melanogaster X chromosomal gene-like 1 protein (Dmxl1), aka Rabconnectin-3A (Rbcn3A). The yeast homologue of Dmxl1, Rav1p, is part of a protein complex that catalyzes the reversible assembly of the V1 and VO domains, thus regulating proton pumping activity. We, therefore, hypothesized that Dmxl1 is an assembly factor for the V-ATPase in mammalian cells. We generated kidney IC-specific Dmxl1 knockout (KO) mice and they had a high urine pH, similar to B1 V-ATPase KO mice, suggesting impaired V-ATPase function. Western blotting of kidney lysates showed decreased B1 V-ATPase expression, but other V-ATPase subunits were normal. B1 (V1 domain) and a4 (VO domain) subunits were immunolocalized in ICs and apical localization quantified using FIJI. Both B1 and a4 were more intracellular in Dmxl1 KO ICs relative to control mice. A Pearson’s correlation analysis of B1 and a4 staining revealed a significant decrease in colocalization in Dmxl1 KO ICs, suggesting reduced B1/a4 assembly. In parallel, subcellular fractionation experiments revealed less V1 domain-associated B1 subunit in the membrane fraction relative to the cytosol. Furthermore, a Proximity Ligation Assay (PLA) was performed using probes against B1 and a4 to confirm decreased assembly of the two domains in KO ICs. When the two probes are within 40 μM of each other, like when the domains are assembled, this results in a fluorescent PLA punctum. As expected, we observed a significant decrease in the area of PLA puncta per cell in KO animals relative to control animals. These data demonstrate that the V-ATPase is less assembled in Dmxl1 KO ICs, relative to controls. We propose that loss of Dmxl1 reduces assembly of the V-ATPase holoenzyme, thereby inhibiting its proton pumping function. Dmxl1 may mediate recruitment of the V1 domain to the membrane and facilitate its assembly with the transmembrane VO domain. In the absence of Dmxl1, V1 is instead targeted for degradation, explaining the inability of these mice to properly acidify their urine. We conclude that Dmxl1 is a bona-fide mammalian V-ATPase assembly factor that functions similarly to its yeast homolog, Rav1p in affecting V-ATPase assembly. NIH/NIDDK R01DK121848 to DB. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

AKAP2 plays a pivotal role in renal acid-base homeostasis during metabolic acidosis

Reversible phosphorylation and dephosphorylation of kidney proteins modulate their activities and localization and play a central role in maintaining fluid and acid-base homeostasis. The proximal tubule and the intercalated cells of the nephron are main sites of acid-base balance. It was previously demonstrated that some kidney transporters involved in the pH homeostasis were regulated by the c-AMP/Protein Kinase A (PKA) signaling pathway.The A-Kinase anchoring protein 2 (AKAP2), is a scaffold protein that binds to the Protein Kinase A (PKA) allowing the phosphorylation of target proteins but is also known to interact with Protein Phosphatase 1 and consequently contributes to protein dephosphorylation. In this study, we hypothesize that AKAP2 regulates the activity and localization of renal transporters during metabolic acidosis. An inducible and nephron-specific Akap2Pax8/LC1 knockout mouse model was generated. Fluorescent immunostaining showed that AKAP2 is present in the tubules mainly at the apical plasma membrane. AKAP2 knock-out mice in normal conditions presented an acidic urine pH and polyuria compared to control mice. Ex-vivo data from micro-perfused CCDs demonstrated a higher Na+ reabsorption and K+ secretion in AKAP2 KO mice. This suggests its importance in maintaining acid-base balance even under physiological conditions. Moreover, when treated with an ammonium chloride diet, KO mice were sensitive to the acid load; showed a lower blood pH, hyperchloremia, a lower bicarbonate level and a two-fold higher blood ammonia. The sensitivity of the KO mice further supports the role of AKAP2 in acid-base homeostasis. Although we think this is due to renal acid-base transporters activity deregulation, the consideration of a potential defect in water reabsorption mechanisms contributing to acidosis is also valid. Our study provides valuable insights into the role of AKAP2 in maintaining fluid and acid-base homeostasis in the kidneys. The findings open avenues for further research into the molecular mechanisms underlying AKAP2-mediated regulation of renal transporters and its impact on acid-base balance. Swiss National Science Foundation (SNSF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in renal acid-base regulation

Transport along the renal tubule differs between female and male rodents, possibly as a consequence of varying abundance and expression of transporters along the nephron. For several aspects such as renal Na+ transport and blood pressure regulation, this has been comprehensively studied; however, data on sex differences in renal acid-base regulation are less well understood. We hypothesized that there will be sex differences in transporter expression profiles in response to acid-base challenges. We used female and male C57Bl/6 mice (n=10 per sex and treatment), which were challenged by acid (NH4Cl, 0.28 mM) and base (NaHCO3, 0.28 mM) in drinking water for 8 days. Blood and urine samples were collected at baseline and at the end of the experimental period before kidneys were harvested under isoflurane anesthesia. Data were analyzed by 2-way ANOVA followed by Tukey multiple comparisons test. In response to NH4Cl challenge, urine pH significantly decreased in both sexes without sex differences (male baseline: 6.4±0.1 vs. NH4Cl: 5.7±0.1; female baseline: 6.2±0.2 vs NH4Cl: 5.6±0.1). In contrast to the urinary response, blood pH was not significantly affected in male mice (male baseline: 7.29±0.01 vs. NH4Cl: 7.26±0.02); however, significantly decreased in female mice (female baseline: 7.28±0.01 vs NH4Cl: 7.22±0.02). Despite differences in acid-base physiology, no differences were observed in the abundance of NHE3, pS552-NHE3, Npt2a, NKCC2, NCC, pT58-NCC or pendrin between sexes. In response to NaHCO3 challenge, urine pH significantly increased in both sexes; however, the increase was significantly smaller in female vs. male mice (male baseline: 6.3±0.1 vs. NaHCO3: 7.6±0.1; female baseline: 6.3±0.1 vs NaHCO3: 7.0±0.3). In contrast to the urinary response, blood pH significantly increased in male mice (male baseline: 7.28±0.01 vs. NaHCO3: 7.40±0.01); however, was not significantly affected in female mice (female baseline: 7.29±0.01 vs NaHCO3: 7.31±0.01). These differences in females compared to males were associated with a significantly greater abundance of Npt2a (~1.5-fold), pendrin (~1.4-fold) and H-ATPase (~1.5-fold). No differences were observed in the abundance of NHE3, pS552-NHE3, NKCC2, NCC, pT58-NCC, between sexes. In summary, our study demonstrates that acid-base regulation shows very specific sex differences: (i) female mice seem to be more prone to a NH4Cl disturbance compared with male mice, (ii) acid challenges under these conditions do not result in major changes in the abundance of the tested proteins, (iii) male mice are more prone to a NaHCO3 disturbance possibly because of (iv) lower abundances of Npt2a, pendrin and H-ATPase. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hematological and biochemical indices, Rumen pH, Ammonia concentration in rumen liquor and Urine pH of white Fulani (Bunaji) bull Yearling calves fed graded levels of urea and molasses ensiled rice straw supplemented with maize offal and cowpea husk

The study was carried out at Duware farm along Yola-Fufore Road Adamawa state. Nigeria to determine the hematological and biochemical indices, rumen pH, ammonia concentration in rumen liquor and urine pH of white Fulani (Bunaji) bull Yearling calves fed graded levels of urea and molasses ensiled rice straw supplemented with maize offal and cowpea husk. Six yearling white Fulani (Bunaji) bull calves weighed 80kg-100kg was used for the research. The treatments diets consist of graded levels of urea and molasses ensiled rice straw supplemented with maize offal in T1, graded levels of urea and molasses ensiled rice straw supplemented with cowpea husk in T2, and graded levels of urea and molasses ensiled rice straw only in T3 (control group). The feeds was offered at 8; 00 am in the morning and 6: 00 pm in the evening, remnants was weight before fresh feeds were offered, mineral lick and water was provided ad-libitum, and animals were weight weekly to determine their growth performance. Two weeks adaptation period was carried out, the experiment last for three months including the adaptation period. Techniques and statistical package for data analysis was completely randomize design (CRD) and the values were subjected to analysis of variance (ANOVA) using least significant difference (LSD) to separate the means. Results revealed that the hematological and biochemical indices PCV, RBC, WBC, HBC, MCV, MCH, MCHC, Total protein, albumin, globulin, creatinine, urea Con. Lymphocytes, Neutrophils, Monocytes were significantly (P<0.05) difference across the treatments means, but are not significantly (P>0.05) difference among T2 and T3 in Eosinophil (%),rumen pH, ammonia concentration in rumen liquor NH3(mg/100ml) and urine pH were not significantly affected (P>0.05) by the inclusion level of urea-molasses in an ensiled rice straw in the diets, it can be concluded that the hematological and biochemical indices fall within the recommended values and white Fulani (Bunaji) bull Yearling calves can be fed graded levels of urea and molasses ensiled rice straw supplemented with maize offal and cowpea husk without any deleterious effects.

A Child with Distal (Type 1) Renal Tubular Acidosis Presenting with Progressive Gross Motor Developmental Regression, Medullary Nephrocalcinosis, and Acute Renal Failure - A Case Report

Background: Distal renal tubular acidosis (dRTA) is a condition characterized by the impaired ability to secrete hydrogen ions from the distal tubule. In pediatric patients, common clinical features of dRTA include excessive urine production (polyuria), frequent nighttime urination (nocturia), poor growth and weight gain (failure to thrive), difficulty with bowel movements (constipation), abnormal breathing, and the presence of kidney stones (nephrolithiasis). While urinary tract infections (UTIs) are frequently associated with dRTA, renal failure is uncommon and seldom reported in children. Case Presentation: A 10-year-old girl was referred for the evaluation due to a progressive loss of gross motor milestones over a period of 3 years. She also experienced an acute episode of paralysis and was found to have bilateral medullary nephrocalcinosis (right staghorn calculus) accompanied by moderate renal failure and a UTI. Her development in other areas was appropriate for her age. Importantly, there was a history suggestive of excessive urine production (polyuria), increased thirst (polydipsia), and frequent nighttime urination (nocturia). Physical examination revealed proximal myopathy, characterized by a waddling gait and a positive Gower’s sign, as well as diminished reflexes and muscle tone in the lower limbs. Laboratory tests indicated the presence of sepsis (total leukocyte count – 26,660, CRP-174.29) and elevated renal parameters (serum creatinine – 4.27) along with active urinary abnormalities. Urine culture and sensitivity testing showed significant growth of Escherichia coli (>100,000 CFU). A computed tomography scan of the kidneys, ureters, and bladder revealed a staghorn calculus on the right side, as well as bilateral medullary nephrocalcinosis and swollen kidneys. The patient was diagnosed with dRTA based on several factors, including hypokalemic hyperchloremic metabolic acidosis with a normal anion gap, high urine pH, borderline hypercalciuria, presence of medullary nephrocalcinosis, and after ruling out other potential differential diagnoses. Following treatment for the UTI and sepsis, as well as standard treatment for dRTA, the child exhibited symptomatic improvement. Her creatinine levels returned to 0.8 mg/dL, and the septic markers declined to normal levels. To further investigate the cause of the initial decline in renal function in addition to the UTI, a renal biopsy was performed. Conclusion: This case report emphasizes the significance of including medullary nephrocalcinosis and renal tubular acidosis in the list of potential diagnoses for patients presenting with progressive gross motor developmental regression, acute flaccid paralysis, and proximal myopathy. Timely identification of these conditions can help avoid unnecessary and expensive investigations, while also facilitating prompt clinical recovery in affected children. Early diagnosis plays a crucial role in guiding appropriate management strategies and improving patient outcomes.

The Rise in Tubular pH during Hypercalciuria Exacerbates Calcium Stone Formation.

In calcium nephrolithiasis (CaNL), most calcium kidney stones are identified as calcium oxalate (CaOx) with variable amounts of calcium phosphate (CaP), where CaP is found as the core component. The nucleation of CaP could be the first step of CaP+CaOx (mixed) stone formation. High urinary supersaturation of CaP due to hypercalciuria and an elevated urine pH have been described as the two main factors in the nucleation of CaP crystals. Our previous in vivo findings (in mice) show that transient receptor potential canonical type 3 (TRPC3)-mediated Ca2+ entry triggers a transepithelial Ca2+ flux to regulate proximal tubular (PT) luminal [Ca2+], and TRPC3-knockout (KO; -/-) mice exhibited moderate hypercalciuria and microcrystal formation at the loop of Henle (LOH). Therefore, we utilized TRPC3 KO mice and exposed them to both hypercalciuric [2% calcium gluconate (CaG) treatment] and alkalineuric conditions [0.08% acetazolamide (ACZ) treatment] to generate a CaNL phenotype. Our results revealed a significant CaP and mixed crystal formation in those treated KO mice (KOT) compared to their WT counterparts (WTT). Importantly, prolonged exposure to CaG and ACZ resulted in a further increase in crystal size for both treated groups (WTT and KOT), but the KOT mice crystal sizes were markedly larger. Moreover, kidney tissue sections of the KOT mice displayed a greater CaP and mixed microcrystal formation than the kidney sections of the WTT group, specifically in the outer and inner medullary and calyceal region; thus, a higher degree of calcifications and mixed calcium lithiasis in the kidneys of the KOT group was displayed. In our effort to find the Ca2+ signaling pathophysiology of PT cells, we found that PT cells from both treated groups (WTT and KOT) elicited a larger Ca2+ entry compared to the WT counterparts because of significant inhibition by the store-operated Ca2+ entry (SOCE) inhibitor, Pyr6. In the presence of both SOCE (Pyr6) and ROCE (receptor-operated Ca2+ entry) inhibitors (Pyr10), Ca2+ entry by WTT cells was moderately inhibited, suggesting that the Ca2+ and pH levels exerted sensitivity changes in response to ROCE and SOCE. An assessment of the gene expression profiles in the PT cells of WTT and KOT mice revealed a safeguarding effect of TRPC3 against detrimental processes (calcification, fibrosis, inflammation, and apoptosis) in the presence of higher pH and hypercalciuric conditions in mice. Together, these findings show that compromise in both the ROCE and SOCE mechanisms in the absence of TRPC3 under hypercalciuric plus higher tubular pH conditions results in higher CaP and mixed crystal formation and that TRPC3 is protective against those adverse effects.

Smartphone-based colorimetric detection platform using color correction algorithms to reduce external interference

Smartphone-based digital image colorimetry is a powerful, fast, low-cost approach to detecting target analytes. However, lighting conditions and camera parameters easily affect the detection results, significantly curtailing its applicability in multiple scenarios. In this study, an Android-based mobile application (SMP-CC) is developed, which offers a comprehensive package that includes image acquisition, color correction, and colorimetric analysis functions. Using a custom color card, a built-in algorithm in SMP-CC can minimize the color difference between the standard color block image captured by different smartphones under different lighting conditions and the standard value by an LS171 colorimeter less than 4.36. The algorithm significantly eliminates the impacts of external lighting conditions and differences in cell phone models. Furthermore, the feasibility of SMP-CC was verified by successful colorimetric detection of urine pH, glucose, and protein, demonstrating its potential in smartphone-based digital image colorimetry.

A Curious Case of Quadriplegia

Background: Hypokalemic periodic paralysis (HPP) is an uncommon disorder of the muscle marked by intermittent weakness of muscles , which, in severe cases, can progress to respiratory failure. It is frequently associated with renal tubular acidosis, a condition that can manifest in connection with systemic disorders like Sjögren’s syndrome and thyroid disorders.  Case Presentation: A 58-years-old woman presented to the hospital with weakness in all extremities. The patient exhibited motor strength of 0/5 in all limbs. The ECG revealed sinus bradycardia and hypokalemia changes. Laboratory tests showed hypokalemia, metabolic acidosis with a high anion gap, urine pH of more than 5.5, FT4 levels at 6.9 ng/dL, TSH levels at 25.03 IU/mL, Anti-TPO antibodies positive, and a positive SS-A (Ro), Ro-52, SS-B (La) in the ANA profile, indicative of Sjogren's syndrome. Patient has previously experienced similar issues and also has a confirmed diagnosis of hypothyroidism.  Discussion: The patient received diagnoses of hypokalemic periodic paralysis(HPP), Sjögren's syndrome, and renal tubular acidosis due to findings of hypokalemia, metabolic acidosis, elevated urine pH, and a positive ANA profile.  Conclusion: Distal renal tubular acidosis secondary to Sjögren’s syndrome can rarely present as HPP.

Distal renal tubular acidosis as a rare complication of vesicoureteral reflux in children: a case report and literature review.

Distal renal tubular acidosis (dRTA) is a clinical picture of hyperchloremic hypokalemic metabolic acidosis with a normal anion gap. It can be caused by a variety of conditions including obstructive uropathy such as vesicoureteral reflux (VUR). We report a rare case of dRTA secondary to VUR in a 4-year-old girl with a history of meningomyelocele, neurogenic bladder and recurrent urinary tract infections. She was admitted to the hospital with complaints of polydipsia, polyuria, and inability to gain weight for the last 1year. She was on prophylactic antibiotic treatment with clean intermittent catheterization and anticholinergic drug. She had a history of subureteral injection of various agents and botulin toxin injection into the bladder. Her voiding cystourethrogram revealed grade 5 VUR in the left kidney, tortuosity in the left ureter, and the bladder had a dome-like appearance and was trabeculated. When all laboratory values of the patient since birth were examined, it was observed that urine pH was high despite hypokalemic hyperchloremic metabolic acidosis for the last year; these abnormalities became more severe in the last few months. In conclusion, the development of hypokalemia and nephrolithiasis/nephrocalcinosis along with metabolic acidosis in a patient diagnosed with VUR should be considered as an indicator of impaired tubular functions. Also, the possibility of an underlying VUR in the presence of recurrent urinary tract infection in a patient diagnosed with dRTA should not be ignored.

Concomitant urea stabilization and phosphorus recovery from source-separated fresh urine in magnesium anode-based peroxide-producing electrochemical cells

In this study, we investigated the recovery of nitrogen (N) and phosphorus (P) from fresh source-separated urine with a novel electrochemical cell equipped with a magnesium (Mg) anode and carbon-based gas-diffusion cathode. Recovery of P, which exists primarily as phosphate (PO43−) in urine, was achieved through pH-driven precipitation. Maximizing N recovery requires simultaneous approaches to address urea and ammonia (NH3). NH3 recovery was possible through precipitation in struvite with soluble Mg supplied by the anode. Urea was stabilized with electrochemically synthesized hydrogen peroxide (H2O2) from the cathode. H2O2 concentrations and resulting urine pH were directly proportional to the applied current density. Concomitant NH3 and PO43− precipitation as struvite and urea stabilization via H2O2 electrosynthesis was possible at lower current densities, resulting in urine pH under 9.2. Higher current densities resulted in urine pH over 9.2, yielding higher H2O2 concentrations and more consistent stabilization of urea at the expense of NH3 recovery as struvite; PO43− precipitation still occurred but in the form of calcium phosphate and magnesium phosphate solids.

Acid-Base Balance in Healthy Adults: Beneficial Effects of Bicarbonate and Sodium-Rich Mineral Water in a Randomized Controlled Trial: The BicarboWater Study.

Noncommunicable diseases (NCDs) are a global health challenge. The complex etiology of NCDs involves genetic, environmental, and lifestyle factors, including dietary habits. Chronic latent metabolic acidosis has been associated with an increased risk of NCDs. Alkalizing diets and mineral water consumption have shown promise in improving acid-base balance and potentially impacting NCDs. In this randomized controlled intervention study, the effect of drinking 1,500-2,000 mL of mineral water daily on acid-base balance was evaluated. Ninety-four healthy participants were divided into two groups: one consumed mineral water with a high bicarbonate and sodium content (HBS, n = 49) and the other consumed mineral water with a low bicarbonate and sodium content (LBS, n = 45). Changes in venous blood gas and urinary acid-base parameters were measured over a short-term (3 days) and long-term (28 days) intervention period. Potential renal acid load (PRAL) and nutrient intake were calculated at baseline and after 28 days. HBS water consumption led to increased urinary pH (24-hour urine and spontaneous urine, both p < 0.001) and bicarbonate levels (p < 0.001), accompanied by reduced titratable acids (p < 0.001) and ammonium (p < 0.001), resulting in a lower renal net acid excretion (p < 0.001). These changes occurred in the short term and persisted until the end of the study. LBS consumption showed no significant effects on urinary pH but led to a slight decrease in bicarbonate (p < 0.001) and NH4 + (p < 0.001), resulting in a slight decrease in NAE (p=0.011). Blood gas changes were modest in both groups. Mineral water consumption in the HBS group altered dietary intake of sodium and chloride, contributing to changes in PRAL values. The study demonstrates that the consumption of mineral water high in bicarbonate and sodium (1,500 mL-2,000 mL/day) can positively influence urinary acid-base parameters and reduce NAE, suggesting potential benefits in maintaining acid-base balance without adverse effects on human health. These findings highlight the importance of mineral water composition in acid-base regulation. This trial is registered with DRKS00025341.

Gaps in kidney stone disease management: From clinical theory to patient reality.

With nephrolithiasis projected to affect 25% of the global population in the next three decades, there is an urgent call for innovative management strategies to prevent and reduce stone recurrence. This study aims to explore the evolving management needs in nephrolithiasis from both patient and healthcare provider perspectives. An expert-collaborative online survey comprising 10 targeted questions on kidney stone management was developed and disseminated. This survey was designed to gather comprehensive insights from patients, physicians and dietician and other person in the field of nephrolithiasis. Analysis of responses from 120 participants, including 45 nephrologists, 38 dieticians, 11 urologists, and 14 kidney stones patients followed in our hospital, revealed critical insights. A significant 97.5% emphasized the necessity of optimizing daily water intake, and 94.1% recognized the need for practical dietary modifications. Additionally, 88.3% of respondents found timely hydration reminders beneficial. Notably, monitoring urine color and pH was valued by 85% and 84.3% of the participants, respectively. A striking disparity emerged in the perception of fatigue and wellness monitoring, with 65% of patients prioritizing fatigue monitoring, a view less shared by healthcare professionals. Similarly, 71% of patients deemed wellness monitoring essential, highlighting a gap in understanding between patients and their caregivers. This study underscores the critical need for more tailored guidance on hydration strategies and the promise of remote urine parameters monitoring in nephrolithiasis management. The findings strongly advocate for a patient-centered approach, aligning medical recommendations with patient lifestyles and experiences, to enhance the effectiveness of nephrolithiasis management.

Nephrolithiasis in Renal Tubular Acidosis: Pathophysiology, Diagnosis, and Management Strategies

Renal tubular acidosis (RTA) encompasses a group of disorders characterized by impaired kidney acid-base regulation, resulting in metabolic acidosis. Nephrolithiasis, the formation of kidney stones, represents a significant complication of RTA. Despite its clinical importance, the relationship between RTA and nephrolithiasis remains complex and poorly understood. This review provides a comprehensive overview of nephrolithiasis in RTA, focusing on its pathophysiology, diagnostic challenges, and management strategies. Mechanisms underlying kidney stone formation in RTA, including altered urinary pH, electrolyte abnormalities, and mineral metabolism disturbances, are explored in detail. Clinical manifestations and diagnostic considerations specific to nephrolithiasis in RTA patients are discussed, emphasizing the importance of a comprehensive metabolic evaluation and imaging procedures for accurate diagnosis. Current therapeutic approaches for treating kidney stones in RTA patients, including dietary modifications, pharmacological interventions, and surgical interventions, are reviewed. By elucidating the intricate interplay between RTA and nephrolithiasis, this review aims to enhance clinical understanding and guide optimal management strategies for patients with this challenging renal disorder.

A nomogram clinical prediction model for predicting urinary infection stones: development and validation in a retrospective study.

This study aimed to develop a nomogram prediction model to predict the exact probability of urinary infection stones before surgery in order to better deal with the clinical problems caused by infection stones and take effective treatment measures. We retrospectively collected the clinical data of 390 patients who were diagnosed with urinary calculi by imaging examination and underwent postoperative stone analysis between August 2018 and August 2023. The patients were randomly divided into training group (n = 312) and validation group (n = 78) using the "caret" R package. The clinical data of the patients were evaluated. Univariate and multivariate logistic regression analysis were used to screen out the independent influencing factors and construct a nomogram prediction model. The receiver operating characteristic curve (ROC), calibration curves, and decision curve analysis (DCA) and clinical impact curves were used to evaluate the discrimination, accuracy, and clinical application efficacy of the prediction model. Gender, recurrence stones, blood uric acid value, urine pH, and urine bacterial culture (P < 0.05) were independent predictors of infection stones, and a nomogram prediction model ( https://zhaoyshenjh.shinyapps.io/DynNomInfectionStone/ ) was constructed using these five parameters. The area under the ROC curve of the training group was 0.901, 95% confidence interval (CI) (0.865-0.936), and the area under the ROC curve of the validation group was 0.960, 95% CI (0.921-0.998). The results of the calibration curve for the training group showed a mean absolute error of 0.015 and the Hosmer-Lemeshow test P > 0.05. DCA and clinical impact curves showed that when the threshold probability value of the model was between 0.01 and 0.85, it had the maximum net clinical benefit. The nomogram developed in this study has good clinical predictive value and clinical application efficiency can help with risk assessment and decision-making for infection stones in diagnosing and treating urolithiasis.

In-Depth Analysis of Diet Diary and Urine pH Measurements Improved Food Diet Reporting in Postmenopausal Women with RUTI.

We proceeded with an in-depth review of diet diaries for nutrient analysis from a cohort of women suffering from uncomplicated recurrent urinary tract infection (RUTI) to validate the accuracy of our current food diet record (FDR) form and evaluate possible domains of improvement. As part of an IRB-approved study, this previously published cohort of NHANES-comparable women was analyzed for consistency of the nutrient intake over 3 days, the influence of the time between meals and urine pH, the effect of nutrient intake over interval time between meals, and seasonal and before/during the COVID-19 pandemic changes. Intrarater reliability for nutrient analysis and intrapatient variability for urine pH were computed to test for consistency. Intrarater reliability for diet analysis was 91% accurate for foods and beverage matching and nutrient analysis. Mean standard deviation of urine pH readings within study participants was 0.4 (95% CI: 0.4, 0.5). An association was noted between total calories and fat consumed at breakfast and an increase in time to lunch. Calories consumed were unaffected across seasons or during the COVID-19 pandemic. Water intake during summer was significantly lower than that during fall and winter (both, p < 0.001). The patients who reported drinking water had a significantly lower average urine pH than women who did not report drinking water (5.8 vs. 6.2; p = 0.026). In this cohort of postmenopausal women with RUTIs, in-depth analysis of our current FDR findings led to several actionable items, which will improve our current food diet self-reporting process by our patients.