Early Morning Urine Research Articles

The development and progression of albuminuria in South Asians with type 2 diabetes compared with Western Europeans. Results from the HinDu the Hague diabetes study.

Although South Asians have an increased risk to develop diabetes, data on the difference in development and progression of diabetic nephropathy between ethnic groups are not consistent. The aim of this study was to evaluate possible differences in the development and progression of albuminuria in South Asians and Western Europeans (WE) with type 2 diabetes in a large closed cohort of South Asians with type 2 diabetes. Data on 1269 South Asians and 2272 Dutch adults with type 2 diabetes who were treated in our diabetes clinic in 2006 or referred thereafter were extracted from electronic medical records. Microalbuminuria and macroalbuminuria were defined separately for men and women based on albumin/creatinine ratios in early morning urine samples. We defined 3 outcomes: (1) no albuminuria, (2) persistent microalbuminuria and (3) macroalbuminuria at the end of follow-up. Cox proportional hazard models were used to discriminate differences in time from diabetes diagnosis until development and progression of albuminuria between the two ethnic groups, adjusted for retinopathy, hypertension, smoking and age at diabetes diagnosis. South Asians have a higher adjusted risk for developing microalbuminuria: HR 1.4, (95% CI 1.2, 1.6) and macroalbuminuria: HR: 1.2 (1.0, 1.4) compared to Western Europeans. However, mean time to progress from micro- to macroalbuminuria was not different between the ethnic groups (3.9 ± 4.0 yrs vs. 3.4 ± 3.9 yrs respectively). South Asians have a higher adjusted risk to develop micro- and macroalbuminuria compared with Western Europeans. When microalbuminuria is present, time to progression from micro- to macroalbuminuria is not different between the two groups.

B-253 Using biomarkers in recurrent renal stone formers to detect silent stones

Abstract Background Glycosaminoglycans (GAGs) protect cells from binding of calcium oxalate (CaOx) crystals to prevent CaOx stone formation. Hyaluronan (HA) is a non-sulfated GAG with crystallization-promoting activity during renal stone formation. The excretion of urinary GAGs and HA were measured in stone-formers (SF), post-treated SF, and normal controls to reveal their relationship with renal stone disease. Methods Three groups were included - active SF, post-treated SF (SF after extracorporeal shock wave lithotripsy) and normal controls with 40 subjects in each group. Early morning urine was collected for each subject. The hexuronate content of the GAGs were measured by carbazole reaction and values for GAGs were standardized against creatinine. Individual GAGs extracts were then digested sequentially with Streptomyces hyaluronidase and chondroitinase ABC to yield the HA disaccharides for analysis by high performance liquid chromatography. Results Hexuronate content of GAGs were in the order of post-treated SF < SF << normal controls. SF had an enhanced urinary excretion of HA with no increase of urinary HA in post-treated SF group. However, both the SF and post-treated SF groups had increased proportion of HA (of total GAGs) compared to normal controls. Active-SF and post-treated SF groups had lower total GAGs content but increased proportion of HA than that of the normal controls indicating that urinary GAGs and HA are probably protective/risk factors, respectively, for renal stone disease. Conclusions The higher recurrence rate of renal stone disease may be due to the presence of sub-species of GAGs, HA, that becomes an accidental participant for renal stone formation. Concomitantly, other species of charged sulfated GAGs, which are protective to the cells and prevent crystal binding, are found to be in lesser content in active SF and post-treated SF. Clinicians can use these two markers, which are easily detectable (by ELISA) for prevention and monitoring of silent renal stone formation.

#2293 Cardiac autonomic neuropathy: an independent risk factor for renal decline in diabetic kidney disease

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the UK and worldwide. Due to its unpredictability and incurable nature, novel risk factors associated with incidence and progression of DKD need to be identified. One such factor is cardiac autonomic neuropathy (CAN). Many studies over last 30 years had demonstrated a significant relationship between CAN and incidence and progression of DKD using estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) as end points. However, no prospective studies have looked into relationship between CAN diagnosed by gold standard cardiac autonomic reflex tests (CARTs) and DKD with different prognostic risks as per KDIGO classification. The aim of the study is to examine this relationship further. Method Data from 91 participants (type 1 and type 2 DM) with eGFR >30 ml/min/1.73 m2 who underwent assessment for CAN using CARTs as per O'Brien's and Ewing's criteria during baseline visits performed between 2007 and 2010 were collected. Additional participants (n = 113) were also recruited in 2021 as part of iBEAt study which is an EU-funded, multi-centre renal imaging study to identify novel biomarkers for DKD. Data analysis for 204 participants in total was performed for this study. CAN was defined as 2 or more abnormal CARTs out of 5 (Table 1). The level of prognostic risk was calculated based on eGFR (G1-G5) and UACR (A1-A3), following KDIGO risk table from 2012 CKD guidelines. eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation and UACR was assessed by early morning urine sample. Participants were categorised as follow: low risk, moderate risk and high risk. Due to limited numbers of participants with G3 in eGFR, we have combined ‘high risk’ and ‘very high risk’ into one group. CAN was divided into 2 groups—with and without CAN. Differences in proportions were examined using chi-square test. The association between baseline CAN and risk of renal decline was assessed using multinominal logistic regression adjusted for baseline age, HbA1c, ACEi/ARBs use, retinopathy status, total cholesterol and triglyceride. If significant differences were found, individual groups were compared by Bonferroni post hoc test. All analyses were performed in SPSS (version 29.0) and correlations were considered significant if p < 0.05. Results We analysed data of 204 participants (130 T1DM, 74 T2DM), 44.6% (n = 91) of them were women, mean (SD) age at baseline visit was 51 (15.7) years, eGFR 82.6 (13) ml/min/1.73 m2, UACR 5.2 (21.8) mg/mmol, duration of diabetes at baseline 19.7 (12.3) years and 36.8% had hypertension. Baseline eGFR and UACR were available for 198 and 193 participants respectively. Of these, 42.9% (85/198) had G1, 47.5 (94/198) had G2 and 9.6 (19/198) had G3. For UACR, 80.8% (156/193) had A1, 15.5% (30/193) had A2 and 3.6% (7/193) had A3. 53.4% (103/204) of participants had CAN and 46.6% (101/204) had no CAN. A higher proportion of participants was in low prognostic risk category 77.8% (154/198), followed by 13.1% (26/198) with moderate risk and 9.8% (18/198) with high risk for CKD progression. The risk of DKD progression was significantly associated with presence of CAN in multinominal logistic regression analysis (p = 0.020). The presence of CAN was closely related to low risk (95% CI: 1.44 to 22.04, p = 0.013) and moderately increased risk (95% CI: 1.03 to 24.7, p = 0.04). The participants with moderate and high risk had lower eGFR (p < 0.001) and higher UACR with increased risk (p < 0.001) (Table 2). This finding was independent of baseline age, HbA1C, retinopathy, ACEI/ARB use, type of diabetes, cholesterol and triglyceride levels at baseline as measured by logistic regression. Conclusion To our knowledge, this is one of the first studies to examine the relationship between presence of CAN in three stages of prognostic risk in DKD. We demonstrated that presence of CAN was an independent risk factor for decline in renal function in DKD. Further large prospective studies are required to confirm the findings of this study and examine the underlying mechanisms how CAN leads to greater risk of DKD.

Point-of-care circulating cathodic antigen positivity and associated factors in school children one year after mass praziquantel administration in an endemic district in Ghana

BackgroundMass drug administration of praziquantel is expected to reduce Schistosome carriage in treated children in endemic communities. However, the effectiveness of this annual exercise has not been assessed in Ghana. Therefore, this study aimed to detect viable Schistosoma mansoni infection using point-of-care circulating cathodic antigen (POC-CCA) positivity as proxy and associated factors in children previously treated with praziquantel in an endemic municipality in Ghana. Materials and methodsThis cross-sectional study was done in the Assin Central municipality in the Central Region of Ghana. School children, less than 16 years of age, treated with 40 mg/kg of praziquantel (treatment period: February–March 2019), provided early morning urine (∼40 mL) and stool (∼4 g) samples. Immediately, POC-CCA (ICT International, South Africa) was done, while S. mansoni ova were detected in formalin fixed samples using microscopy later. Additionally, participant's socio-demographic information and factors associated with S, mansoni infection transmission were collected from each child. ResultsA total of 520 children participated in the study (males-51.9%, majority age range [9–11 years, 34.4%]). Overall, 244 (46.9%) were positive for urinary CCA with no S. mansoni detected by microscopy. POC-CCA positivity was higher in females (48.4%), children with 2–3 siblings (49.3%), children aged 6–8-year range (55.4%) and residents of Brofoyedur (52%). However, age (x2 = 16.1, p = 0.0003) and town of residence (x2 = 11.7, p = 0.019) associated with CCA positivity. Further, location of water body (x2 = 16.4, p = 0.008), frequency of water contact (x2 = 12.3, p = 0.015) and handling of the Biomphalaria intermediate host (x2 = 5.1, p = 0.024) associated with POC-CCA outcome. ConclusionAbout 47% of the school children were positive for CCA, one year after mass praziquantel administration in the Assin Central municipality. Varied factors associated with the post-praziquantel administration POC-CCA positivity. This study should be replicated in other endemic areas to identify groups at risk of parasite persistence or reinfection to inform modification of control and preventive measures.

Diagnostic accuracy of Lipoarabinomannan detection by lateral flow assay in pleural tuberculosis

BackgroundLipoarabinomannan (LAM) antigen serves as an attractive biomarker to diagnose Tuberculosis (TB). Given the limitations of current diagnostic modalities for Pleural TB, current study evaluated LAM’s potential to serve as a point-of-care test to diagnose pleural TB.MethodsA cross sectional, diagnostic accuracy study was conducted during February to November 2021 in a tertiary care hospital in India. LAM antigen detection was performed on pleural fluid as well as early morning urine specimen of suspected pleural TB patients by “Alere/ Abott Determine TB LAM” lateral flow assay (LAM-LFA). The results were compared to microbiological reference standards/MRS (Mycobacterial culture or NAAT) and Composite reference standards/CRS (MRS plus Clinico-radiological diagnosis).ResultsA total of 170 subjects were included in the analysis, including 26 with Definite TB, 22 with Probable TB, and 122 with No TB. Compared to MRS and CRS, the sensitivity (61.54% & 45.83%) and positive predictive value (PPV) (57.14 & 78.57%) of Pleural LAM-LFA testing were found to be suboptimal, whereas the specificity (91.67% & 95.08%) and negative predictive value (NPV) (92.96% & 81.69%) of the assay were found to be good. Urinary LAM-LFA performed even worse than pleural LAM-LFA, except for its higher specificity against MRS and CRS (97.2% and 98.3%, respectively). Specificity and PPV of pleural LAM detection increased to 100% when analysed in a subgroup of patients with elevated ADA levels (receiver operating curve analysis-derived cut off value > 40 IU/ml).ConclusionDetection of LAM antigen by LFA directly from pleural fluid was found to be a useful test to predict absence of the disease if the test is negative rather than using as a POCT for diagnosis.

Exploring the Utility of Urinary Creatinine Adjustment for KIM-1, NGAL, and Cystatin C for the Assessment of Kidney Function: Insights from the C-KidnEES Cohort.

Normalization of urinary biomarkers of kidney injury is a common practice in clinical and research settings to account for variations in urine concentration, and urinary creatinine is often used as a reference. However, to date, there is no consensus on the adjustment of urinary biomarkers with creatinine, and both absolute and creatinine-adjusted biomarker levels are adopted for making interpretations of kidney health. Hence, the present study aimed to investigate the associations of urinary creatinine with three widely used kidney injury biomarkers, KIM-1, NGAL, and cystatin C, to validate the applicability of urinary creatinine as a reference for normalization. A cross-sectional study was performed with 2100 students, 10-18 years of age in the Children's Kidney Environmental Exposure Study (C-KidnEES) cohort established in Sri Lanka. As identified in linear regression analyses, normalization of urinary KIM-1, NGAL, and Cys-C to urinary creatinine did not result in significant under-adjustment or over-adjustment to the absolute urinary concentrations, giving no specific rationale for creatinine adjustment. Hence, absolute urinary concentrations of the above biomarkers can be adopted for the characterization of subclinical kidney injury in adolescents in community studies where early morning urine sampling is practiced. However, for spot urine samples, consideration of both absolute and creatinine-adjusted biomarker levels would be a better approach.

Prevalence of Trichomonas vaginalis infections amongst female students’ of tertiary institutions in Ogun State, Nigeria

Trichomonas vaginalis is a parasitic protozoan and the causative agent responsible for vaginal trichomoniasis in women. Trichomoniasis is a sexually transmitted disease with significant public health impacts with vaginitis, cervicitis, urethritis, and pelvic inflammatory disease. TV also affects birth outcomes and is known to be associated with human immune deficiency virus transmission and its acquisition. A cross-sectional study was undertaken; it involves 250 female undergraduate students assessed for Trichomonas vaginalis infection. Fifteen milliliters of early morning urine samples were collected with a sterile disposable universal bottle, the trophozoites presence observed within 10 min of samples collection. The urine samples were centrifuged at 25 ℃ for 13 min at 1,500 rpm. Wet-mount microscopy examination performed using a drop of vortex sediments from the urine samples for their appearances, if bloody or cloudy and also screened for the presence of trophozoites of Trichomonas vaginalis. 56 (22.4%) were within the age bracket of 17 – 21 years, 124 (49.9%) were of the age range of 22 – 26 years, 42 (16.8%) were in the age group of 27 – 31 years, and 28 (11.2%) were 31 years and above. The rate of infections was significantly varied by age group, with the highest being in sexually active young women aged between 22–26 years 10 (80.7%) and the lowest in the age group 31 years (7.1%). It concluded that Trichomonas vaginalis control should be a public health authorities concern that can manage multiple health inequalities noted in some less privileged towns and villages in Nigeria.

884-P: Decentralized N=1 Study—A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin

Background: The SGLT2 inhibitor dapagliflozin reduces kidney function decline and urine albumin:creatinine ratio (UACR) on a population level. However, there is marked heterogeneity in the efficacy among individual patients. We conducted a decentralized (i.e. at home) N=1 trial to assess the effect of dapagliflozin in individual patients and the feasibility of remote data collection. Methods: Twenty patients with type 2 diabetes, UACR >20 mg/g and eGFR >30 mL/min/1.73m2 entered the randomized placebo-controlled double-blind N=1 trial. Patients were randomly assigned to two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with 1-week wash-out periods in between. Patients collected and sent their own data with automatic uploading to an online platform and sent early morning urines 5 times/week to the laboratory for albumin and creatinine assessment. Primary outcome was UACR change from baseline (mixed effects model). The study had 80% power to detect a correlation in UACR change between first and second dapagliflozin period of 0.6. Results: Patients had a mean eGFR of 70.2 mL/min/1.73m2 and median UACR of 94.7 mg/g. During the study, dapagliflozin compared to placebo reduced albuminuria by 15.1% (95%CI 3.3 - 28.2; p=0.013). There was a marked variation in the change from baseline in UACR during dapagliflozin treatment periods (range first and second exposure -26.9 to -4.7% and -30.5 to -5.8%, respectively). The individual change in UACR during the first and second exposure correlated in the dapagliflozin periods (r=0.50; p=0.026) but not in the placebo periods (r=0.09; p=0.69). Of all scheduled urine collections (N=816), only 5 collections (0.61%) were not delivered in the laboratory. Conclusion: The individual UACR response to dapagliflozin varies among individual patients and is consistent upon re-exposure. Remote data collection was very reliable with nearly any missed urine collection. Disclosure J.Beernink: None. G.D.Laverman: Advisory Panel; AstraZeneca, Vifor Pharma Management Ltd., Boehringer Ingelheim Inc., Astellas Pharma Inc., Lilly, Other Relationship; Sanofi, AstraZeneca. H.L.Heerspink: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Bayer Inc., Eli Lilly and Company, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., George Clinical, Merck & Co., Inc., Janssen Research & Development, LLC, Traveere Pharmaceuticals, Novo Nordisk. N.Jongs: Speaker's Bureau; AstraZeneca.

Urinary abnormalities in asymptomatic secondary school children in Calabar, Nigeria

Introduction: Many patients with kidney disease are asymptomatic but may have abnormalities in urine. The aim of this study was to determine the prevalence of urinary abnormalities (UA) in asymptomatic secondary school children in Calabar, Nigeria and its relationship with age, sex, social class, body mass index and blood pressure.
 Methodology: It was a descriptive cross sectional study of 407 apparently healthy secondary school children aged 10-18 years recruited by multistage sampling techniques in June-July, 2022. Semi-structured questionnaires were used to obtain their bio-data and clinical history. Subject’s height and weight were measured using a stadiometer and body mass index (BMI) calculated. Blood pressure of each subject was measured using auscultatory method. Early morning urine was obtained from each subject and urinalysis done using dipstick- combi 10. The result of urinalysis was recorded. Data were analyzed using SPSS version 22.0 and p- value ≤ 0.05 was significant.
 Results: Out of 407 participants, 162 (39.8%) were males and 245 (60.2%) females giving a M:F ratio 1:1.5. The mean age was 13.5 ± 1.9 years. The prevalence of urinary abnormalities was 115 (28.3%) with many having more than one abnormality. Age group 13-15years were more commonly affected. Nitrituria 75(18.4) was the most frequent urinary abnormality followed by proteinuria 38 (9.3%), leucocytes14 (3.4%) andhaematuria 5(1.2%). There was no glucosuria. Nitrituria was statistically significant among females (p=0.040). Blood pressure, overweight and obesity were not statistically significant in relation to urinary abnormalities.
 Conclusion: The prevalence of urinary abnormalities was high among secondary school children but commoner in females and mainly nitrituria, proteinuria, leucocytes and haematuria. We therefore recommend regular screening for urinary abnormalities among secondary school children in our environment for early detection and prevention of renal diseases

Pre-Discharge Urinary Albumin-Creatinine Ratio as a Predictor of Post-Hospitalization Major Adverse Cardiovascular Events (MACEs) Due to Acute Heart Failure

Background: Acute heart failure (AHF) is a multifactorial syndrome associated with rehospitalization and higher mortality. Impaired renal function is one of non-cardiac comorbidities which aggravate the progression of heart failure (HF). Increased in urinary albumin-creatinine ratio (UACR) reflects decline of renal function. It also provides useful information for risk stratification and determining prognosis of HF patient. Methods: Patients with AHF who met inclusion-exclusion criteria were included in a prospective observational cohort study. After achieving decongestion state, we obtained early morning urine samples of these patients to examine pre-discharge UACR. We monitored patients within 60 days post-discharged. Demographic, clinical characteristics, comorbidities, laboratory and echocardiographic data were also collected. The outcomes studied were major cardiovascular events (MACEs), consisted of rehospitalization due to heart failure and/or cardiovascular mortality. Cut-off point of pre-discharge UACR was determined by ROC curves, Kaplan-Meier curve was used to assess survival of MACEs based on pre-discharge UACR values, and multivariate analysis using Cox Regression was performed using SPSS version 24.0.0.0. Results: A total of 70 samples were involved until the end of the study. The cut-off point of pre-discharge UACR was 46.5 mg/gram creatinine (AUC 0.653, sensitivity of 67.5% specificity of 66.7%). Subjects with pre-discharge UACR ≥46.5 mg/gram creatinine had a survival of 39.40% while those with a value <46.5 mg/gram creatinine had a survival of 73.0% (p = 0.003). Multivariate analysis showed that pre-discharge UACR ≥ 46.5 mg/gram creatinine was independently associated with an increased risk of MACEs within 60 days post-hospitalization due to AHF (adjusted HR 4.76; 95% CI 1,455-15,622; p=0.010). Conclusion: Pre-discharge UACR ≥ 46.5 mg/gram creatinine was independently associated as a predictor of MACEs within 60 days post-hospitalization due to AHF.

A comparison of the utility of the urine dipstick and urine protein-to-creatinine ratio for predicting microalbuminuria in patients with non-diabetic lifestyle-related diseases -a comparison with diabetes

BackgroundThe utility of dipstick proteinuria for predicting microalbuminuria in non-diabetic lifestyle-related diseases compared with the urine protein-to-creatinine ratio (uPCR) and the effect of dipstick proteinuria on the cut-off value (CO) and accuracy of uPCR are unclear.MethodsThe subjects included Japanese patients ≥ 18 years old with lifestyle-related diseases who had an estimated glomerular filtration rate of ≥ 15 ml/min/1.73 m2 and uPCR of < 0.5 g/gCr at initiation. Urine dipstick, uPCR and urine albumin-to-creatinine ratio (uACR) were measured three times per case. Microalbuminuria was defined as uACR of 30–299 mg/gCr for at least 2 of 3 measurements. Youden’s Index was used as the optimal CO. Factors associated with microalbuminuria were analyzed using a logistic regression model.ResultsIn 313 non-diabetic cases (median 70.8 years old), 3 dipstick proteinuria measurements were independently useful for detecting microalbuminuria, and the CO was set when a trace finding was obtained at least 1 of 3 times (sensitivity 0.56, specificity 0.80, positive predictive value [PPV] 0.73, negative predictive value [NPV] 0.65). A single uPCR measurement was more useful than 3 dipstick measurements, and was useful for detecting microalbuminuria even in cases with three consecutive negative proteinuria findings, indicating that the CO of the second uPCR with G1-3a (n = 136) was 0.06 g/gCr (sensitivity 0.76, specificity 0.84. PPV 0.68, NPV 0.89), while that with G3-b4 (n = 59) was 0.10 g/gCr (sensitivity 0.56, specificity 0.91. PPV 0.83, NPV 0.71). The sum of 3 uPCRs was useful for detecting microalbuminuria in cases with G1-3a (sensitivity 0.67, specificity 0.94, PPV 0.82, NPV 0.86) and G3b-4 (sensitivity 0.78, specificity 0.94, PPV 0.91 NPV 0.83), with both COs being 0.23 g/gCr. These COs of microalbuminuria did not change when trace or more proteinuria was included, although the sensitivity increased. A high uPCR and low urine specific gravity or creatinine level were independent factors for uACR ≥ 30 mg/gCr in cases with negative proteinuria, although the uPCR was a major predictive factor of a uACR ≥ 30 mg/gCr.ConclusionsThe uPCR (preferably determined using early-morning urine), including in dipstick-negative proteinuria cases with non-diabetic lifestyle-related diseases, can aid in the early detection of microalbuminuria.Trial registrationRetrospectively registered.

TUBERCULAR TESTICULAR ABSCESS: A CASE REPORT

Objective: This study aims to provide fellow physicians a better insight in diagnosing and managing similar cases. Case(s) Presentation: A 36 year old male presented to the emergency department with a chief complaint of red, painful, and progressively enlarging swelling of the left scrotal pouch since 1 week ago. The patient had a history of similar complaint and recurrent cloudy urine which were left untreated 1 year before. Based on physical examination and ultrasonography findings, the patient was diagnosed with left scrotal abscess and was treated by incisional drainage of abscess and necrotomy debridement under spinal anesthesia. Discussion: Tuberculosis infection of scrotal contents is rare and occurs in approximately 7% of the patients with tuberculosis, although tuberculosis itself is a global epidemic with more than 2 billion of the world population infected. In patients with genital tuberculosis, pulmonary and renal tuberculosis can be documented in 50% and 80-85% respectively. It is often secondary to the pre-existing tuberculosis of the urinary tract, which may be confirmed by the culture of early morning urine specimens. Conclusion: Treatment of testicular abscess is administration of appropriate antibiotics according to its causative organism accompanied by surgical drainage. Early diagnosis and prompt treatment of testicular abscess is necessary, since chronic and severe cases, as happened in this patient, usually resulted in nonviable testicular tissue and necessitate orchidectomy. This may be due to cumulative ischemia of the testicles from multiple mechanisms: inflammatory infiltration causing compression of the spermatic cord, thrombosis secondary to venous congestion and/or bacterial exotoxins.&#x0D;

P-026: FACTORS ASSOCIATED WITH RENAL DYSFUNCTION AMONG CHILDREN WITH SICKLE CELL DISEASE

Purpose: Sickle cell nephropathy is a major complication of sickle cell disease and microalbuminuria is an early predictor of renal damage. Hence it is important to study the prevalence of renal dysfunction and its associated clinical, biochemical, and nutritional factors, benefitting patients in early identification and appropriate intervention thus, preventing the renal complications and associated morbidity. Materials and methods: A cross sectional study was conducted considering a total of 163 patients between 5-20 years, with SCD (homozygous) of either sex, diagnosed using HPLC attending outpatient clinic in their steady state for routine clinical care at a tertiary care hospital. Patients with history of blood transfusion within 2 weeks or in acute crisis or febrile illness were excluded from the study. Random spot urine sample was used for estimation of microalbuminuria by immunoturbidimetry method. Demographic details, clinical, biochemical, and nutritional parameters of each were recorded, analysed and compared. Microalbuminuria was said to be present if urine albumin creatinine ratio was between 30-300 mg/gm urine creatinine and value more than 300 mg/gm of urine creatinine was labelled as macroalbuminuria. A positive screening test was repeated twice with an early morning urine sample before labelling patient as having microalbuminuria. eGFR estimation was done using modified schwartz formula. Results: Out of total 163 patients (5-20 years), majority (32.52%) were in the age group of 6.1-9 years followed by 5-6 years (31.29%). Male female ratio was 1.3:1. Mean BMI was 14.67 ± 2.32. Mean VOC episodes and mean number of blood transfusions were 3.25 ± 2.91 and 3.23 ± 4.39 respectively. 3 patients had macroalbuminuria (1.84%), microalbuminuria was found in 24 patients (14.72%) while 83.44% patients were normal. 71.8% patients had normal eGFR, 18.4% had hyperfiltration while 9.8% had mild decrease in eGFR. The mean age was significantly higher in children with microalbuminuria than in those without microalbuminuria (11.69 ± 3.86 vs 8.55 ± 3.59 years; P=0.001), youngest patient being 6-year-old. Amongst positive patients, 66.67% were males and 33.33% were females. However, no significant correlation was found between gender and microalbuminuria (P= 0.293). 70.8% of positive patients had ≥3 episodes of vaso-occlusive crisis during their lifetime (P= 0.028) which was found to be statistically significant. Blood pressure taken at first visit were within normal limits for all the patients. 75% patients were already on hydroxyurea at the time of enrolment. 16.67% patients with microalbuminuria had hyperfiltration, 12.5% had mild decrease in eGFR while 70.83% had normal eGFR. No significant correlation was found between patient’s eGFR, nutritional status, blood transfusion frequencies, acute febrile illness episodes or any laboratory parameters with microalbuminuria. Conclusion: Age and frequent episodes of vaso-occlusive crises were found to be major factors associated with occurrence of microalbuminuria. These results confirm the need for early screening of microalbuminuria in patients with sickle cell disease and will be helpful in designing target strategy for early identification and introduction of appropriate timely intervention (drugs like ACE inhibitors) so that long term renal complications can be prevented. The authors do not declare any conflict of interest

Diagnostic toolkit for tuberculosis: should we include urine lipoarabinomannan (LAM) detection in the WHO European Region?

Diagnostic toolkit for tuberculosis: should we include urine lipoarabinomannan (LAM) detection in the WHO European Region?

Proteomic analysis of urinary exosomes from patients with lithium‐induced nephrogenic diabetes insipidus

Lithium (Li)‐induced Nephrogenic Diabetes Insipidus (NDI) is a large healthcare problem, which affect around 40% of patients with bipolar disorder undergoing Li treatment. NDI is characterized by the inability in the kidney to concentrate urine in response to vasopressin in the kidney collecting duct (CD). In animals, Li causes a downregulation of aquaporin‐2 and a cellular remodeling of the CD in rats resulting in a reduced fraction of principal cells relative to intercalated cells. Whether Li has similar effects in the human kidney is, however, not known. Urinary exosomes are extracellular nanovesicles derived from intracellular multivesicular bodies fused with the plasma membrane of epithelial cells lining the kidney tubular system and the urinary tract. The purpose of the first part of this study is to analyze whether the urinary rat proteome reflects the Li‐induced changes in the kidney. This is followed by proteomic analyses of urinary exosomes isolated from Li‐NDI patients.Rats were divided in three groups; controls (n=8), 2‐week Li treatment (40 mmol/kg/food, n=8) and 4‐week Li treatment (40 mmol/kg/food, n=8). Treatment with Li showed a significant increase in urine output after 2‐weeks (P&lt;0.01) and 4‐weeks (P&lt;0.05). Additionally, the rats developed severe polydipsia, with water intake significantly increased after 2‐weeks Li treatment (P&lt;0.001) and 4‐weeks Li treatment (P&lt;0.0001).Early morning urine samples from the placebo group in a previous published 12‐week placebo‐controlled pilot trial (Fotso Soh et al, 2021. A double‐blind, randomized, placebo‐controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users. Bipolar Disorders 23, 66–75) involving Li‐NDI patients (n=9) were collected. The Li‐NDI participants have been on a stable dose of Li (˃2 months) and determined to have a urinary osmolality &lt;600 mOsm/kg at baseline. In addition, urine from random healthy controls (n=6) were collected. Urine samples from the rodent study and human study were subjected to ultracentrifugation for exosome isolation and will be further processed for mass spectrometry analysis (MS/MS).

Diagnostic Accuracy of Urine Lipoarabinomannan Testing in Early Morning Urine versus Spot Urine for Diagnosis of Tuberculosis among People with HIV.

ABSTRACTThe Fujifilm SILVAMP TB LAM (FujiLAM) assay offers improved sensitivity compared to Determine TB LAM Ag (AlereLAM) for detecting tuberculosis (TB) among people with HIV. Here, we examined the diagnostic value of FujiLAM testing on early morning urine versus spot urine and the added value of a two-sample strategy. We assessed the diagnostic accuracy of FujiLAM on cryopreserved urine samples collected and stored as part of a prospective cohort of adults with HIV presenting for antiretroviral treatment in Ghana. We compared FujiLAM sensitivity and specificity in spontaneously voided urine samples collected at inclusion (spot urine) versus in the first voided early morning urine (morning urine) and for a one (spot urine) versus two samples (spot and morning urine) strategy. Diagnostic accuracy was determined against both microbiological (using sputum culture and Xpert MTB/RIF testing of sputum and urine to confirm TB) and composite reference standards (including microbiologically confirmed and probable TB cases). Paired urine samples of spot and morning urine were available for 389 patients. Patients had a median CD4 cell count of 176 cells/μL (interquartile range [IQR], 52 to 361). Forty-three (11.0%) had confirmed TB, and 19 (4.9%) had probable TB. Overall agreement for spot versus morning urine test results was 94.6% (kappa, 0.81). Compared to a microbiological reference standard, the FujiLAM sensitivity (95% confidence interval [CI]) was 67.4% (51.5 to 80.9) for spot and 69.8% (53.9 to 82.8) for morning urine, an absolute difference (95% CI) of 2.4% (−10.2 to 14.8). Specificity was 90.2% (86.5 to 93.1) versus 89.0% (85.2 to 92.1) for spot and morning urine, respectively, a difference of 1.2% (−3.7 to 1.4). A two-sample strategy increased FujiLAM sensitivity from 67.4% (51.5 to 80.9) to 74.4% (58.8 to 86.5), a difference of 7.0% (−3.0 to 16.9), while specificity decreased from 90.2% (86.5 to 93.1) to 87.3% (83.3 to 90.6), a difference of −2.9% (−4.9 to −0.8). This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice.IMPORTANCE This study indicates that FujiLAM testing performs equivalently on spot and early morning urine samples for detecting tuberculosis among people with HIV. Sensitivity could be increased with a two-sample strategy but at the risk of lower specificity. These data can inform future guidelines and clinical practice around FujiLAM.

Effect of diuretics on kidney stone-forming risk – an investigation using multiple timed urine collections

Introduction: Thiazide diuretics can lower urinary calcium excretion, helping to prevent recurrent calcium kidney stones. As dietary intake and urine chemistry varies throughout the day, a 24-h urine collection may not provide sufficient information to guide the optimal management in individual patients. Using multiple timed urine collections, we sought to identify times during the day when stone-forming risk is higher, allowing for therapy to be more accurately targeted. Methods: In a prospective study, healthy adult volunteers took a 4-week course of either hydrochlorothiazide (HCTZ) 25 mg/d or indapamide 2.5 mg/d. They were assessed at baseline, and at days 7, 14 and 28. At each time point, blood samples were taken for analysis and multiple timed urine samples were collected throughout the day, together with one overnight sample. Results: Diuretic treatment was well tolerated. Daily calcium and citrate excretion decreased, while ionized calcium and phosphate excretion were unchanged. Ionized calcium-divalent phosphate and ionized calcium-oxalate products were unchanged. In the timed urine samples, calcium excretion was decreased, particularly by indapamide, in the morning. Indapamide, but not HCTZ, decreased urinary citrate excretion, most obviously in overnight and early morning urines. No changes in ionized calcium were observed. Decreased divalent phosphate excretion was observed at several time points in the indapamide group. The ionized calcium-divalent phosphate product tended to decrease at most time points in both groups but no significant changes were observed in the ionized calcium-oxalate product. Conclusions: Indapamide 2.5 mg/d has a stronger protective effect against forming calcium kidney stones than HCTZ 25 mg/d. Most of the benefits appear to be achieved during the daytime and it may therefore be beneficial to prescribe medication twice daily or in the evening to maximize the protective effects of these agents. The benefits of indapamide treatment were attenuated by a reduction in urinary citrate excretion, an effect which has not been previously described. Keywords: hydrochlorothiazide, indapamide, kidney stones, urine collection

Excretion Patterns of Urinary Sediment and Supernatant Podocyte Biomarkers in Patients with CKD.

Podocyte depletion causes glomerulosclerosis, and persistent podocyte loss drives progression to ESKD. Urinary sediment podocin (u-sed Pod) mRNA excretion and urinary supernatant podocalyxin (u-sup PCX) protein have been used to monitor disease activity in glomerular diseases. However, the differences in these markers among pathologies have not been investigated. We examined the roles of these markers in kidney diseases. From January 2013 to March 2016, early morning urine samples were collected from 12 healthy controls and 172 patients with kidney disease (n=15 patients with minor glomerular abnormality with mild proteinuria and/or microscopic hematuria, n=15 with minimal change nephrotic syndrome [MCNS], n=15 with membranous nephropathy [MN], n=60 with IgA nephropathy [IgAN], n=19 with crescentic GN [Cres GN], n=10 with lupus nephritis [LN], and n=38 with other kidney diseases). We examined u-sed Pod mRNA excretion, u-sup PCX protein, and the urinary protein-creatinine ratio (u-PCR). u-sed Pod mRNA excretion was significantly correlated with u-sup PCX protein (r=0.37, P<0.001). Both u-sed Pod mRNA excretion and u-sup PCX protein were significantly correlated with u-PCR (r=0.53, P<0.001 and r=0.35, P<0.001, respectively). Interestingly, u-sed Pod mRNA excretion was significantly increased in proliferative-type GN-including IgAN with extracapillary proliferative lesions, Cres GN, and LN class IV-and significantly correlated with the rate of crescent formation, whereas u-sup PCX protein was significantly increased only in those with MN and subepithelial dense deposit-type LN compared with controls. Higher u-sed Pod mRNA excretion and u-sup PCX protein were associated with proliferative-type GN, indicating podocyte detachment and subepithelial dense deposit-type GN, respectively. The results suggest that u-sed Pod mRNA excretion and u-sup PCX protein have usefulness for the diagnosis and measurement of disease activity with regard to glomerular diseases.

Relationship Between Microalbuminuria and Risk Factors for Cardiovascular Diseases Among Secondary School Student in Ilorin, Nigeria

Introduction: Globally, cardiovascular diseases (CVDs) are the leading causes of deaths with more than half due to coronary heart disease linked with the development of atherosclerosis. Hypertension (HTN) and obesity are leading risk factors for atherosclerotic CVDs, presence of which is predicted by microalbuminuria (MA). We wanted to evaluate the relationship between microalbuminuria and risk factors for CVDs (obesity, overweight, pre-hypertension and hypertension) among secondary school students in Ilorin, North central Nigeria. Methods: We conducted a descriptive, cross-sectional study from December 2017 to March 2018 among secondary school students. We recruited 584 students, aged 10 to 18 years from 14 schools across the three Local Government Areas (LGAs) in Ilorin. We measured their blood pressure and anthropometrics following standard protocols and determined microalbuminuria in their early morning urine using Microalbumin 2-1 Combo strip and spot urinary albumin - creatinine ratio. Results: The prevalence of MA was 30.1%. MA was more common in obese and hypertensive adolescents (p &lt; 0.001 and p &lt; 0.01 respectively). Occurrence of MA correlated strongly with subject’s weight (r = 0.790, p = 0.004, p &lt; 0.01); systolic blood pressure (r = 0.884, p = 0.001, p &lt; 0.01) and body mass index (r = 0.710, p = 0.001, p &lt; 0.01). Independent predictors of MA were obesity, adjusted odds ratio (aOR) 4.9, (95% CI 1.124, 20.913), overweight (aOR 3.6, 95% CI 1.184, 10.174), older age (aOR 1.1, 95% CI 1.007, 1.219) and presence of systolic hypertension (aOR 3.1, 95% CI 1.903, 5.042). Conclusions: This study shows a high prevalence of MA among the adolescents. CVDs risk factors predictive of MA are overweight, obesity, systolic hypertension and older age.

The associations of nitrated polycyclic aromatic hydrocarbon exposures with plasma glucose and amino acids

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) have been widely studied for their mutagenic and carcinogenic effects. This study aims to investigate whether exposure to nitro-PAHs is associated with biomarkers of carbohydrate metabolism, an underlying risk factor for metabolic disorder. Early morning urine and blood samples were longitudinally collected two times with a four-week interval from 43 healthy adults. Five urinary amino-PAHs (1-aminonaphthalene, 2-aminonaphthalene, 9-aminophenanthrene, 2-aminofluorene, and 1-aminopyrene) were measured as biomarkers of nitro-PAH exposures. We measured plasma concentrations of glucose and six amino acids that can regulate insulin secretion, including aspartate (Asp), glutamate (Glu), glutamine (Gln), alanine (Ala), Arginine (Arg), and ornithine (Orn). We found that increasing concentrations of 9-aminophenanthrene were significantly associated with increasing glucose levels and with decreasing Asp, Glu, Ala, and Orn levels. We estimated that 26.4 %–43.8 % of the 9-aminophenanthrene-associated increase in glucose level was mediated by Asp, Glu, and Orn. These results suggest that exposure to certain nitro-PAHs affects glucose homeostasis, partly resulting from the depletion of insulin-stimulating amino acids (Asp, Glu, and Orn).