Urinary Acid Research Articles

NHE3 in the thick ascending limb is required for sustained but not acute furosemide-induced urinary acidification.

Na+/H+ exchanger isoform 3 (NHE3) facilitates Na+ reabsorption and H+ secretion by the kidneys. Despite stronger NHE3 abundance in the thick ascending limb (TAL) compared with the S1 and S2 segments of the proximal tubule, the role of NHE3 in the TAL is poorly understood. To investigate the role of NHE3 in the TAL, we generated and phenotyped TAL-specific NHE3 knockout (NHE3TAL-KO) mice. Compared with control mice, NHE3TAL-KO mice did not show significant differences in body weight, blood pH, or plasma Na+, K+, or Cl- levels. Fluid intake trended to be higher and urine osmolality was significantly lower in NHE3TAL-KO mice. Despite a similar glomerular filtration rate, NHE3TAL-KO mice had a greater urinary K+-to-creatinine ratio. One proposed role of NHE3 relates to furosemide-induced urinary acidification. Acute bolus treatment with furosemide under anesthesia did not result in differences in the dose dependence of urinary flow rate, Cl- excretion, or maximal urinary acidification between genotypes; however, in contrast with control mice, urinary pH returned immediately toward baseline levels in NHE3TAL-KO mice. Chronic furosemide treatment reduced urine osmolality similarly in both genotypes but metabolic alkalosis, hypokalemia, and calciuresis were absent in NHE3TAL-KO mice. Compared with vehicle, chronic furosemide treatment resulted in greater Na+-K+-2Cl- abundance regardless of genotype. Na+-phosphate cotransporter 2a abundance was also greater in furosemide-treated control mice compared with vehicle treatment, an effect that was absent in NHE3TAL-KO mice. In summary, NHE3 in the TAL plays a role in the sustained acidification effect of furosemide. Consistent with this, long-term treatment with furosemide did not result in metabolic alkalosis in NHE3TAL-KO mice.NEW & NOTEWORTHY Na+/H+ exchanger isoform 3 (NHE3) is very abundant in the thick ascending limb (TAL) compared with the proximal tubule. Much has been learned about the role of NHE3 in the proximal tubule; however, the function of NHE3 in the TAL remains elusive. A novel mouse model that lacks NHE3 selectively in the TAL not only shows a phenotype under baseline conditions but also identifies that NHE3 is required for sustained but not acute furosemide-induced urinary acidification.

Acidification of 24-hour urine in urolithiasis risk testing: An obsolete relic?

BackgroundRecommendations on the optimal preservation of 24 h urine for the metabolic work-up in urolithiasis patients are very heterogeneous. In case two such tests with different storage condition recommendations are being analysed, multiple collections would be needed, challenging especially elderly and very young patients. We therefore aimed to evaluate the stability of urine constituents under different storage conditions. Material and methodsWe collected urine samples from ten healthy volunteers and prepared aliquots to be stored either at room temperature or 4 °C. Some aliquots were preserved using hydrochloric acid prior to storage, some thereafter, some using the BD Urine preservation tube and some were not preserved at all. Storage duration was 0, 24, 48 or 72 h. In all samples calcium, magnesium, phosphorus, creatinine, oxalate, citrate and uric acid were measured and compared to the according reference sample. ResultsWe could not find any significant deviation for any of the analytes and preanalytical treatment conditions compared to the associated reference sample. ConclusionPreservation of 24 h urine for the metabolic evaluation in stone formers might not be necessary for sample storage up to 72 h.

Diagnostic problem of Primary Hepatic Neuroendocrine Tumor in 18-year-old woman: A case report.

Introduction and importancePrimary Hepatic Neuroendocrine Tumor (PHNET) is a very rare case and it's quite challenging to diagnose and treat. There are approximately 300 cases reported. Among them, only two giant PHNET cases were found in children under 20 years old.Case presentationWe reported an unusual giant PHNET that was found in 18 years old female followed by intra-tumoral bleeding, which was initially misdiagnosed as Hemangioma. Abdominal Computed Tomography (CT) imaging showed a large liver mass with the peripheral enhancing nodular solid part in the delayed phase, which resembled Hemangioma.Clinical discussionPreoperative diagnosis of a Primary Hepatic Neuroendocrine Tumor is difficult as the liver often becomes the site of Neuroendocrine Tumor metastasis from other gastrointestinal organs, rarely occurred in people under 20 years of age, and the CT scan looks like Hemangiomas. The clinical symptoms are not typical, so other specific diagnostic tools for Neuroendocrine Tumor such as Chromogranin A level and 24-hour 5-hydroxyindoleacetic acid urine test are not performed. The indication of hepatic resection is made based on the preoperative diagnosis of other conditions such as large tumor size or tumor complications. Intraoperative diagnosis is also not typical for PHNET, so the definitive diagnosis of PHENT is made from post-resection histopathology.ConclusionThe preoperative diagnosis of this rare tumor is still a big challenge. The physicians should be alert when finding Giant Hemangioma of the Liver, and Neuroendocrine Tumor should be the differential diagnosis. Blood Chromogranin A, urine 5-hydroxyindoleacetic acid test, and Positron Emission Tomography (PET) scan should also be considered.

Chemical Analysis Study of Kidney Stones in Iraqi Community

The urinary tract system is one of the most important system in human body to control many functions and get any wastes out of body, many diseases may affect this function and prevents it to work effectively. One of this disease is nephrolithiasis at which salt forming stone are settled in renal system affecting its work. The qualitative biochemical analysis of compositions of each stone was done for carbonate, calcium, magnesium, phosphate, oxalate, uric acid, and cysteine, using stone powder derived from the stones. These results found that Calcium oxalate stones were more likely to be detected in patients with upper urinary tract stones (p < 0.001). It was observed in 5.3% of cases which was apparently lower than previous data in nationwide urinary stone composition analysis. the most common type of stone was calcium oxalate (84.1%); others were calcium oxalate phosphate (8.0%), ammonia (3.4%), calcium uric acid (2.3%) and calcium carbonate (1.1%). A defect in ammonium excretion would account for the undue urinary acidity; then, increased urine acidity promotes uric acid super saturation. The amount of urinary oxalate excretion is a significant factor in the development of CaOx stones. Aim of study to know how to prevent stone recurrence and formation requiring better knowing mechanisms contributed in this stone formation.

Effect of Supplementation on Levels of Homovanillic and Vanillylmandelic Acids in Children with Autism Spectrum Disorders.

Autism Spectrum Disorders (ASD) are characterized by numerous comorbidities, including various metabolic and nutritional abnormalities. In many children with ASD, problems with proper nutrition can often lead to inadequate nutrient intake and some disturbances in metabolic profiles, which subsequently correlate with impaired neurobehavioural function. The purpose of this study was to investigate and compare the relationship between supplementation, levels of homovanillic acid (HVA) and vanillylmandelic acid (VMA) and the behaviour of children with ASD using quantitative urinary acid determination and questionnaires provided by parents/caregivers. The study was carried out on 129 children between 3 and 18 years of age. HVA and VMA were extracted and derivatized from urinary samples and simultaneously analyzed by gas chromatography-mass spectrometry (GC-MS). In addition, parents/caregivers of children with ASD were asked to complete questionnaires containing information about their diet and intake/non-intake of supplements. The application of the Mann–Whitney U test showed a statistically significant difference between the level of HVA and vitamin B supplementation (p = 1.64 × 10−2) and also omega-6 fatty acids supplementation and the levels of HVA (p = 1.50 × 10−3) and VMA (p = 2.50 × 10−3). In some children, a reduction in the severity of autistic symptoms (better response to own name or better reaction to change) was also observed. These results suggest that supplementation affects the levels of HVA and VMA and might also affect the children’s behaviour. Further research on these metabolites and the effects of supplementation on their levels, as well as the effects on the behaviour and physical symptoms among children with ASD is needed.

FC012: Urinary Lithogenic Profile in Patients with Non-Alcoholic Fatty Liver Disease

Abstract BACKGROUND AND AIMS Several epidemiological studies have observed an increased risk for nephrolithiasis in patients affected by non-alcoholic fatty liver disease (NAFLD). However, the urinary lithogenic risk profile for patients with NAFLD is currently unknown. METHOD We systematically analysed the urinary metabolic profile of patients affected by NAFLD and liver cirrhosis (LC), followed at the hepatology outpatient clinic of our institution, compared to healthy individuals. A complete metabolic work-up for kidney stone disease was performed in all subjects. Multivariable linear regression models adjusted for age, sex, body mass index, eGFR and diabetes, were applied to assess differences in urinary lithogenic risk factors between healthy individuals and patients affected by NAFLD and LC. RESULTS A total of 42 patients and 12 healthy individuals were included in the analysis. No differences in age, sex and BMI were found among patients affected by NAFLD and LC, whereas the latter were more diabetic (71.4% versus 14.3%). After adjusting for multiple confounders, patients with NAFLD and LC had lower urinary magnesium (−55 mg/24 h; 95% CI −104, −6; P = 0.03 and −63 mg/24 h; 95% CI −121, −6; P = 0.03, respectively) and borderline oxalate (−1.21 mg/24 h; 95% CI −2.42, −0.01; P = 0.05 and −1.42 mg/24 h; 95% CI −2.79, −0.04; P = 0.04, respectively) excretions, compared with healthy controls. Compared with LC patients, NAFLD patients showed higher urinary ammonia (539 mEq/24 h; 95% CI 245, 833; P < 0.01), ammonia/net acid excretion ratio (0.40; 95% CI 0.18, 0.62; P < 0.01), urine pH (1.16; 95% CI 0.44, 1.88; P = 0.05) and lower urinary uric acid excretion (−210 mg/24 h; 95% CI −419, −0.29; P < 0.01) and titratable acidity (−9.7 mEq/24 h; 95% CI −19.0, −0.4; P = 0.04). CONCLUSION Altered urinary ammonia and magnesium excretions seems to be involved in the higher risk for stone formation found in patients with NAFLD. More studies are needed to investigate stone phenotypes and renal handling of ammonia in this setting.

MO437: Decreased Urinary Citrate Levels as a Marker of Progressive Deterioration of Glomerular Filtration in Patients With Autosomic Dominant Polycystic Kidney Disease (ADPKD)

Abstract BACKGROUND AND AIMS In a previous work we have found that there is a reduction in urinary citrate levels in autosomic dominant polycystic kidney disease (ADPKD) patients. Their levels are related to GFR but not serum bicarbonate levels. Our aim was to analyse whether there is any relationship between rate of GFR deterioration and citraturia in ADPKD patients. METHOD We collected routinary determinations of urine citrate in 24-h urine samples and analysed its predictive role for GFR deterioration with general linear modelling. RESULTS We included 94 patients, 42 ± 14 years old, 59.6% men and 40.4% women. Follow-up from citrate determination 55 ± 28 months (range 16–119). Baseline data: urea 40.2 ± 12.3, Cr 1.15 ± 0.38 mg/dL, GFR 78 ± 26 mL/min/1.73 m2. Bicarbonate 25.1 ± 2.5 (18.2–29.2) mEq/L. Final GFR: 69 ± 32 mL/min/1.73 m2. GFR variation: −2.23 ± 4.14 mL/min/year (range −13.7 to 10). We classified patients according to urinary citrate tertiles (≤117, 117 to ≤ 303, >303 mg/gCr). GFR was different at baseline (67.5 ± 27.9, 74.3 ± 24.3, 92.4 ± 19.7, respectively, P < 0.001) and at final observation (51.1 ± 31.8; 71.4 ± 30.1; 85.3 ± 24.9, respectively P < 0.001). There were no differences in albuminuria or proteinuria at baseline, but there were differences in uric acid serum levels and urine output. There were no differences in follow-up time. We observed that GFR rate was different according to tertiles: −4.62 ± 3.66, −0.58 ± 2.78 and −1.53 ​​± 4.74 mL/min/year, respectively (P < 0.001). When comparing CKD by stages, we found that patients with citrate ≤ 117 mg/gCr showed higher GFR rates than when they had higher levels: CKD1 −7.74 ± 3.37, CKD2 −4.5 ± 4.4, CKD3 −3.04 ± 1.79 versus citrate patients > 117 mg/gCr with deterioration < 2 mL/min/year (P < 0.05). With multivariate analysis, we found that final GFR was positively associated with baseline GFR and negatively with age, follow-up time and citrate levels ˂ 117 mg/gCr. CONCLUSION Urinary citrate levels decrease as GFR reduction is observed in ADPKD. The reduction of urinary citrate to values ≤ 117 mg/gCr is associated with faster deterioration of renal function in patients with ADPKD.

Oxidative Stress and Inflammation Contribute to Kidney Injury Risk During Prolonged Passive Extreme Heat Exposure

IntroductionKidney injury is a top cause of hospitalization during extreme heat events. Currently, wet bulb temperatures (Twet) during extreme heat events rarely exceed 31°C. However, it is predicted that Twet during future extreme heat events will exceed 34˚C, the limit of compensability in humans. We previously reported that, compared to a Twet of 31˚C, an 8 h resting exposure to a Twet of 34˚C elevated the risk of kidney injury risk, as quantified via the FDA‐approved kidney injury risk biomarker – the product of urine insulin‐like growth factor binding‐protein 7 and urine tissue inhibitor of metalloproteinases 2 ([IGFBP7·TIMP‐2]). This kidney injury risk is likely of tubular origin, and while the mechanisms underlying this extreme heat mediated tubular injury are unknown, an inflammatory etiology occurring secondary to oxidative stress has been speculated.PurposeTest the hypothesis that kidney injury risk during prolonged passive extreme heat exposure is contributed to by oxidative stress and inflammation.MethodsFifteen healthy men underwent 8 h resting exposures in Twet of 31°C and 34°C. Blood and urine samples were collected at 0 and 8 h. Following observations of elevations in [IGFBP7·TIMP‐2] in 34°C vs. 31°C (p<0.01), assays were conducted for urine liver‐type fatty acid binding‐protein (uL‐FABP ‐ a marker of tubular injury caused by oxidative stress), urine thiobarbituric acid reactive substances (uTBARS ‐ a marker of renal oxidative stress), urine interleukin‐18 (uIL‐18 ‐ a marker of tubular injury and inflammation), and plasma interleukin‐17a (pIL‐17a ‐ a circulating marker of inflammation, n=10). Serum TBARS (sTBARS) was measured to assess systemic oxidative stress. Data are reported as a change from 0 h (mean ± SD). Urine markers were normalized to urine flow rate.ResultsuL‐FABP increased in 34°C (+42 ± 64 ng/min, p<0.01) but not 31°C (+11 ± 20 ng/min, p=0.75) and was different between trials at 8 h (p<0.01). uTBARS increased in 34°C (+43 ± 37 nmol/min, p<0.01) but not 31°C (+14 ± 13 nmol/min, p=0.27) and was different between trials at 8 h (p<0.01). sTBARS did not change in 34°C (+1.2 ± 4.0 nmol/mL, p=0.08) nor 31°C (+0.3 ± 2.9 nmol/mL, p=0.92) and did not differ between trials at 8 h (p=0.16). uIL‐18 increased in 34°C (+27 ± 19 pg/min, p<0.01) and 31°C (+20 ± 25 pg/min, p<0.01) and was higher in 34°C at 8 h (p=0.05). pIL‐17a increased in 34°C (+199 ± 90 fg/dL, p<0.01) but not 31°C (+9 ± 96 fg/dL, p=0.94) and was different between trials at 8 h (p<0.01).ConclusionIncreases in uL‐FABP and uTBARS, in the absence of differences in sTBARS, support that renal tubular injury in 34°C is likely due to oxidative stress. pIL‐17a is selectively elevated in ischemic kidney injury. Thus, elevations in pIL‐17a in 34°C indicates inflammation of renal origins and this was translated to greater increases in uIL‐18 in 34°C. These findings support that kidney injury risk during prolonged passive extreme heat exposure is contributed to by oxidative stress and inflammation.

Description of the Molecular and Phenotypic Spectrum of Lesch-Nyhan Disease in Eight Chinese Patients.

Background: Lesch-Nyhan disease (LND) is a rare disorder involving pathogenic variants in the HPRT1 gene encoding the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) that result in hyperuricemia, intellectual disability, dystonic movement disorder, and compulsive self-mutilation. The purpose of the present study was to characterize the genetic basis of LND and describe its phenotypic heterogeneity by identifying the variation in the HPRT1 gene in a cohort of Chinese LND patients. Results: The median age at diagnosis was 31 mo (interquartile range (IQR): 7–76 mo), and the initial manifestations were mainly head control weakness and motor development delay. The median age of self-mutilation behavior onset was 19 mo (IQR: 17–24 mo), and all patients were required to travel in a wheelchair and fall into the predicament of compulsive self-harm behavior. There were two patients whose blood uric acid levels were normal for their high urinary acid excretion fraction without taking uric acid-lowering drugs. Seven different pathogenic variants of the HPRT1 gene were identified among eight independent pedigrees, including four novel mutations [c.299 (exon 3) T > A; loss (exon: 6) 84 bp; c.277_281delATTGC; c.468_470delGAT]. The pathogenic variant sites were mainly concentrated in exon 3, and truncating mutations (including frameshift mutations and nonsense mutations) were the most common genetic variant types (5/7, 71.4%). Conclusion: The present study described the phenotypic and molecular spectrum of LND in eight Chinese families, including four novel mutations, which expands our understanding of LND.

Claudins in kidney health and disease.

Claudins are strategically located to exert their physiologic actions along with the nephron segments from the glomerulus. Claudin-1 is normally located in the Bowman’s capsule, but its overexpression can reach the podocytes and lead to albuminuria. In the proximal tubule (PT), claudin-2 forms paracellular channels selective for water, Na+, K+, and Ca2+. Claudin-2 gene mutations are associated with hypercalciuria and kidney stones. Claudin-10 has two splice variants, -10a and -10b; Claudin-10a acts as an anion-selective channel in the PT, and claudin-10b functions as a cation-selective pore in the thick ascending limb (TAL). Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin-14 polymorphisms have been linked to increased risk of hypercalciuria. Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. Hypercalciuria and magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins. In the TAL, stimulation of calcium-sensing receptors upregulates claudin-14 and negatively acts on the claudin-16/19 complex. Claudin-3 acts as a general barrier to ions in the collecting duct. If this barrier is disturbed, urine acidification might be impaired. Claudin-7 forms a nonselective paracellular channel facilitating Cl– and Na+ reabsorption in the collecting ducts. Claudin-4 and -8 serve as anion channels and mediate paracellular Cl– transport; their upregulation may contribute to pseudohypoaldosteronism II and salt-sensitive hypertension.

A Comprehensive Proteomics Analysis of Urinary Extracellular Vesicles Identifies a Specific Kinase Protein Profile as a Novel Hallmark of Medullary Sponge Kidney Disease

Recent advances in the high-throughput technologies and data analysis have led to better understanding of the biological processes involved in several kidney disorders,1,S1,S2 including the medullary sponge kidney (MSK) disease, a rare congenital malformation characterized by dilation of the collecting ducts in the renal papillae, urinary acidification and concentration defects, cystic anomalies of precalyceal ducts associated with a high risk of nephrocalcinosis, and recurrent kidney stones.2

Ibuprofen-Associated Hypokalemia and Metabolic Acidosis: Systematic Literature Review.

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug, which has been occasionally associated with hypokalemia and metabolic acidosis. The objective of this report is to analyze the literature on this issue and to address the underlying pathophysiology. Excerpta Medica, the National Library of Medicine, and Web of Science were searched from inception to July 16, 2021. Papers reporting individually documented humans on ibuprofen with hypokalemia, acidosis, or both were retained. Data were extracted using a checklist. For the final analysis, we evaluated 41 reports describing 50 cases (26 males and 24 females; 36 adults and 14 children) with often profound hypokalemia, acidosis, or both after ingestion of ibuprofen. Twenty-six cases were acute and 24 long term. Hypokalemia and acidosis occurred not only after ingestion of very high doses but also after ingestion of moderately high or even normal doses of ibuprofen. Laboratory values consistent with an excessive urinary potassium excretion or an altered urinary acidification were often disclosed in most cases. Discontinuation of ibuprofen resulted in a resolution of hypokalemia and acidosis within days in 47 cases. The course was lethal in 3 cases. This review highlights potentially fatal side effects of ibuprofen and can help doctors who are confronted with such a situation. These data highlight the potential of ibuprofen to occasionally induce hypokalemia and acidosis of renal origin. Discontinuation of ibuprofen results in a resolution within days.

Association of acidic urine pH with impaired renal function in primary gout patients: a Chinese population-based cross-sectional study

BackgroundPatients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood.MethodsA 2016–2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have “primary gout”, based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 <pH≤ 5.5, 5.5 <pH< 6.2, 6.2 ≤pH≤ 6.9, and pH >6.9), aligning with the clinical significance of urine pH.ResultsOverall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria.ConclusionsApproximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.

Acidic Urine Is Associated With Poor Prognosis of Upper Tract Urothelial Carcinoma.

PurposeTo assess the prognostic role of acidic urine (low urine pH) in upper tract urothelial cancer (UTUC).Materials and MethodsWe reviewed patients enrolled in Seoul National University Prospectively Enrolled Registry for Urothelial Cancer-Upper Tract Urothelial Cancer (SUPER-UC-UTUC) who underwent surgical resection from March 2016 to December 2020 in Seoul National University Hospital (SNUH). Patients with non-urothelial cancer or those who are in condition at end-stage renal disease were excluded. Acidic urine was defined as urine pH ≤ 5.5.ResultsA total of 293 patients with a mean age of 70.7 ± 9.5 years were enrolled in this study. Pre-operative laboratory results showed a mean estimated glomerular filtration rate (eGFR) of 64.1 ± 19.2 mL/min/1.73m2 and a mean urine pH of 5.86 ± 0.66. Patients were subdivided into low (pH ≤ 5.5) and high (pH > 5.5) urine pH for comparison. As a result, all variables were comparable except for the T stage, which was significantly higher in the low urine pH group (p = 0.017). Cox regression analysis was performed to assess the clinical impact of acidic urine on patient survival. Multivariate Cox regression analysis revealed that tumor multifocality (HR 2.07, p = 0.015), higher T stage (HR 1.54, p = 0.036), lymphovascular invasion (HR 1.69, p = 0.033), eGFR < 60 mL/min per 1.73 m2 (HR 1.56, p = 0.017), and acidic urine (HR 1.63, p < 0.01) independently decreased disease-free survival (DFS), while multifocality (HR 9.50, p < 0.01), higher T stage (HR 9.51, p = 0.001) and acidic urine (HR 10.36, p = 0.004) independently reduced the overall survival (OS).ConclusionsAcidic urine is independently associated with reduced DFS and OS in UTUC. Acidic urine contributing to acidic environment may promote acquisition of agressive behavior of UTUC.

Treatment of urinary tract infections with the ketogenic diet of H. Cabot. Lancet 20, 1932 g.

The acidic urine reaction caused by diet is much more valid than that caused by drugs. Acidic urine does not irritate the bladder; on the contrary, the irritation caused by the infection is mitigated by the increase in acidity.

Are the levels of uric acid associated with biometeorological conditions?

Hyperuricemia is an independent risk factor for renal and cardiovascular diseases and is closely associated with gout episodes. It is caused, inter alia, by nutritional habits and genetic factors, and also displays seasonal variability conditioned by meteorological factors. The impact of meteorological factors, including both cold and heat stress, on the human physiology is presented based on the Universal Thermal Climate Index (UTCI) – a biometeorological index derived from an analysis of human thermal balance. The aim of our study was to establish whether seasonal variations significantly affect routinely measured urine acid (UA) levels and could eventually support the clinical decision making process, as well as assessing whether UTCI values are correlated with UA levels in blood serum. This work presents a retrospective epidemiological study of data collected in Olsztyn (Poland). Study material comprised 54,536 results of ambulatory tests measuring UA levels, performed during the period 2016–2019. The analysis concerned correlations between UA and the ages of female and male subjects as well as existing biometeorological conditions as represented by UTCI values in an annual cycle. UA levels in females were found to be lower (4.94 ± 1.37 SD) as compared to those of males (6.13 ± 1.43 SD) and demonstrated a strong positive correlation with age. UA values differed significantly (p < 0.05) on days characterized by cold stress and heat stress, for the oldest age group. UA levels were found to differ depending on the season, but these relationships were not statistically significant, except for significantly higher UA levels in females in autumn (p < 0.001). However, there was an evident difference in population UA levels under cold stress conditions (lower) and heat stress conditions (higher) in the elderly. The UTCI is an adequate predictor of population variations in UA levels since it takes into account the variability of local meteorological conditions.

The Role of Acidic Urine on Detrusor Pressure in Patients with Overactive Bladder: A Urodynamic Evaluation.

To evaluate the relationship between urine pH value and urodynamic parameters in patients with overactive bladder. The patients' data whose underwent standard urodynamic study at two tertiary centers in our city. The period between January 2015-January 2021 was reviewed retrospectively. The inclusion criteria were the patients with overactive bladder, over 18 years of age, and with urine analysis before urodynamic study. Patients were divided into two groups as those with acidic urine pH (Group 1) and without (Group 2). The detrusor pressures obtained from filling cystometry were compared between the groups. In addition, the correlation between detrusor pressure and urine pH was examined. The data from 211 patients (109 females, 102 males) were analyzed during the screening period. Eighty-two patients were in Group 1 and 129 patients in Group 2. The mean age was similar between the groups (p = 0.244). The bladder volume at first sensation of filling and urodynamic maximal bladder capacity was lower in Group 1 than Group 2 (p = 0.004; p < 0.001, respectively). The maximum detrusor pressure was higher in the acidic urine pH group (Group 1, 55.8 ± 20.6) than non-acidic urine pH group (Group 2, 14.5 ± 10.2), and it was statistically significant (p < 0.001). In addition, a significant negative correlation was observed between urine pH level and detrusor pressure (p < 0.001). The presence of acidic urinalysis is associated with many urodynamic findings. Significantly, the patients with detrusor overactivity had more acidic urine than without detrusor overactivity. Therefore, for patients with high detrusor pressure, urinalysis should be evaluated carefully.

A Rare Case of Purple Urine Bag Syndrome Presenting with Delirium and Associated with Acidic Urine and UTI due to Serratia Marcescens: But Do We Still Know Enough?

Purple Urine Bag Syndrome (PUBS) is a rare occurrence characterised by a striking purple to blue/violet discolouration of the urine bag and its tubing after long-term indwelling urinary catheterisation while the urine inside remain clear. This phenomenon is a warning sign of Urinary Tract Infection (UTI). However, unlike traditional UTIs, such patients can be nonverbal and asymptomatic with purple/blue urine bag being the only signal for UTI. Tryptophan-Indigo hypothesis is advanced to explain the mystery behind this phenomenon. A rare case of PUBS in acidic urine in an octagenarian (80 years old) female patient, with right sided hemiparesis, hypertension, Post Stroke Aphasia (PSA) and delirium is presented here. Moreover, her urine culture yielded an opportunistic bacteria Serratia marcescens which is not a typical organism responsible for this condition. The bluish colour of urine bag disappeared after hydration, change of the catheter along with urine bag and antibiotic therapy. To the best of the author’s knowledge, this is the first case of PUBS reported from the state of Assam. It is hoped that this case report will be valuable in raising awareness and educating health care providers about this rather unknown esoteric syndrome in this region.

Transient Type 3 Renal Tubular Acidosis during Cyclic Vomiting Syndrome

Type 3 renal tubular acidosis is a pathological condition characterized by the simultaneous occurrence of distal renal tubular acidosis, which causes urinary acidification disorders, and proximal renal tubular acidosis, which causes impaired reabsorption of bicarbonate ions. Type 3 renal tubular acidosis is considered rare. A 5-year-old boy was admitted to our hospital because of frequent vomiting, poor vitality, and fever. He was diagnosed with cyclic vomiting syndrome. Type 3 renal tubular acidosis was also diagnosed because of severe mixed metabolic acidosis with impaired urinary acidification, a low tubular phosphorus reabsorption rate with hypophosphatemia, low-molecular-weight proteinuria, pan-aminoaciduria, and glucosuria. Fluid infusion was performed. On the second day of hospitalization, the vomiting disappeared and the patient was able to eat and drink. He was discharged on the eighth day of hospitalization. The laboratory test abnormalities associated with the renal tubular acidosis gradually improved, and testing at discharge on the eighth day of admission showed no metabolic acidosis, hypophosphatemia, low-molecular-weight proteinuria, or glucosuria. These findings suggested that the type 3 renal tubular acidosis was transient. Severe metabolic acidosis was observed in this patient because of both normal anion gap metabolic acidosis due to type 3 renal tubular acidosis and anion gap metabolic acidosis due to cyclic vomiting syndrome. Although type 3 tubular acidosis is rare, the resultant metabolic acidosis worsens when combined with a disease that causes metabolic acidosis. Type 3 tubular acidosis should be ruled out when severe metabolic acidosis is present.

Frequency and types of transfusion reactions in pediatric population: A report from a tertiary care center in Pakistan

Background: A transfusion reaction is an untoward reaction following blood transfusion. It can be immediate or delayed and further sub-classified into immune and nonimmune. The role of physicians and paramedical staff is important in recognition of reaction and notifying transfusion services by sending relevant material for workup. Objective: The aim of the current study is to see frequency and types of transfusion reactions in pediatric population in a tertiary care center. We also assessed the compliance of clinical staff to send the proper transfusion reaction workup in required time. Materials And Methods: This retrospective cross-sectional study was conducted in the section of hematology and transfusion medicine of a tertiary care hospital in Karachi, from January 2020 to December 2021 after the approval from Ethical Review Committee. The data were analyzed using SPSS version 20. Results: Of the 21,230 units dispensed and transfused, 36 (0.17%) transfusion reactions were noted. Allergic was the most frequent type 21 (58.3%). Red cells accounted for 28 (77.8%) of the reactions. In all cases, reaction forms were completely filled. Blood bags, posttransfusion ethylenediaminetetraacetic acid samples and urine samples in only 8 (22.2%) cases were received at blood bank within 2 h of reaction. Conclusion: Incidence of transfusion reactions was 1 in 590 units transfused. Allergic reactions were most common. No acute hemolytic or septic reaction noted. Practices regarding submission of transfusion reaction form along with required workup to the blood bank need improvement.