Crescents in primary glomerulonephritis: a pattern of injury with dissimilar actors. A pathophysiologic perspective.

Cellular crescents are defined as two or more layers of proliferating cells in Bowman's space and are a hallmark of inflammatory active glomerulonephritis and a histologic marker of severe glomerular injury. In general, the percentage of glomeruli that exhibit crescents correlates with the severity of kidney failure and other clinical manifestations of nephritic syndrome. In general, a predominance of active crescents is associated with rapidly progressive glomerulonephritis and a poor outcome. The duration and potential reversibility of the underlying disease correspond with the relative predominance of cellular or fibrous components in the crescents, the initial location of the immunologic insult inside the glomerulus, and the sort of involved cells and inflammatory mediators. However, the presence of active crescents may not have the same degree of significance in the different types of glomerulopathies. The pathophysiology of parietal cell proliferation may have dissimilar origins, underscoring the fact that the resultant crescents are a non-specific morphological pattern of glomerular injury with different implications in clinical prognosis in the scope of glomerular diseases.

The association of microhematuria with mesangial hypercellularity, endocapillary hypercellularity, crescent score and renal outcomes in immunoglobulin A nephropathy.

BACKGROUND: Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores. METHODS: In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf). RESULTS: Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P < 0.05 for all) compared with patients without microhematuria. Of the 125 patients, 72 had follow-up data available. An increase in the degree of microhematuria was significantly associated with an eGFR decline of -0.81 mL/min/1.73 m2 [95% confidence interval (CI) -1.44 to -0.19, P = 0.01], after adjusting for follow-up time, proteinuria and T score. Severe microhematuria (≥21 RBCs/hpf) was associated with an even larger decline in eGFR (-3.99 mL/min/1.73 m2; 95% CI -6.9411 to -1.0552, P = 0.008), after similar adjustments. CONCLUSION: Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.

Assessment of the correlation of commonly used laboratory tests with clinical activity, renal involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies.

BACKGROUND: The aim of the study was to assess the correlation of commonly used laboratory tests with clinical activity, degree of kidney involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies. METHODS: The study included 28 patients with active AAV (BVAS ≥ 3). The following tests were performed: MPO-ANCA, PR3-ANCA, peripheral blood count, ESR, CRP, procalcitonin, creatinine, GFR, urea, albumin, fibrinogen, d-dimer, components of the C3 and C4 complement systems, urinalysis with sediment evaluation and diurnal proteinuria. The assessments were conducted twice: at study entry (A0) and after 6 months (A6) (BVAS = 0). RESULTS: At the time of inclusion in the study, the mean creatinine concentration was 3.39 mg/dl (GFR 33.17 ml/min/1.73 m²), after achieving remission in 11 patients (39.3 %) GFR remained below 30 ml/min/1.73 m², 4 patients (14.3 %) continued renal replacement therapy, and 3 patients (10.7 %) with advanced renal failure died. Microscopic hematuria occurred in 80.9 % of the studied population, withdrew in most patients, strongly correlated with renal involvement p < 0.001 and was not related to disease severity p = 0.147. CRP, ESR, fibrinogen, d-dimer, albumin and hemoglobin in the peripheral blood showed a strong correlation with the clinical activity of AAV and well identified severe patients. High procalcitonin concentrations correlated with a severe form of the disease, pulmonary involvement with respiratory failure and alveolar hemorrhage (mean 3.41 ng/ml, median 0.91 ng/ml, SD 7.62, p = 0.000), and were associated with the occurrence of infectious complications and the need to administer antibiotic therapy. ANCA antibodies were useful in the evaluation of patients with AAV, the amount of antibodies did not correlate with the severity of vasculitis (p = 0.685) and the results in many patients did not match the expected assumptions. CONCLUSIONS: CRP, ESR, fibrinogen, d-dimers, albumin and hemoglobin in the peripheral blood correlate well with the activity of vasculitis and identify severe patients. The resolution of microscopic hematuria suggests remission of the disease in the renal area. Procalcitonin may be slightly increased in patients with active AAV without infection, high concentrations are strongly associated with infectious complications. ANCA antibodies should always be interpreted in the context of the observed clinical symptoms.

[The asymptomatic microhematuria in the physician's practice].

The review article presents data on: a) definition of microhematuria and diagnosis; b) prevalence estimation and causes of the asymptomatic microscopic hematuria; c) diagnostic approaches for the first time identified of microhematuria; d) follow-up monitoring of patients with asymptomatic hematuria; e) feasibility of medical screening for microhematuria. The analysis includes recommendations of Russian and foreign urological associations, the results of cohort and observational studies, previous study reviews. The identification of 3 or more red blood cells during microscopic examination should be considered microhematuria. There is no uniform examination algorithm for all patients. The basic principle is an individual diagnostic tactic, taking into account the anamnesis, age, concomitant diseases and risk factors. The purpose of a comprehensive examination is to exclude life-threatening conditions (malignant neoplasms and/or glomerular kidney damage). In some cases, after research, the cause of microhematuria remains unclear and monitoring is required. Routine screening of the population in order to detect microhematuria is currently not justified.

Prevalence of microhematuria in renal colic and urolithiasis: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aims to investigate the prevalence of microhematuria in patients presenting with suspected acute renal colic and/or confirmed urolithiasis at the emergency department. METHODS: A comprehensive literature search was conducted to find relevant data on prevalence of microhematuria in patients with suspected acute renal colic and/or confirmed urolithiasis. Data from each study regarding study design, patient characteristics and prevalence of microhematuria were retrieved. A random effect-model was used for the pooled analyses. RESULTS: Forty-nine articles including 15'860 patients were selected through the literature search. The pooled microhematuria prevalence was 77% (95%CI: 73-80%) and 84% (95%CI: 80-87%) for suspected acute renal colic and confirmed urolithiasis, respectively. This proportion was much higher when the dipstick was used as diagnostic test (80 and 90% for acute renal colic and urolithiasis, respectively) compared to the microscopic urinalysis (74 and 78% for acute renal colic and urolithiasis, respectively). CONCLUSIONS: This meta-analysis revealed a high prevalence of microhematuria in patients with acute renal colic (77%), including those with confirmed urolithiasis (84%). Intending this prevalence as sensitivity, we reached moderate values, which make microhematuria alone a poor diagnostic test for acute renal colic or urolithiasis. Microhematuria could possibly still important to assess the risk in patients with renal colic.

Clinical Characteristics of Ratborne Seoul Hantavirus Disease.

Although Seoul orthohantavirus is the only globally spread hantavirus pathogen, few confirmed human infections with this virus have been reported in Western countries, suggesting lower medical awareness of the milder, transient, and often chameleon-like symptoms of this zoonosis. We describe lesser known clinical and laboratory characteristics to help improve underreporting of this virus.

An overlap of Alport syndrome and rheumatoid arthritis in a patient and literature review.

BACKGROUND: Alport syndrome is a rare genetic kidney disease, and rheumatoid arthritis as a common autoimmune disease also causes renal lesions in addition to arthritis. The overlap of them has rarely been reported. CASE PRESENTATION: A 44-year-old man had a history of multi-joint swelling and pain for more than half a year. His laboratory data with double positive for rheumatoid factor and anticitrullinated protein antibodies further supported the diagnosis of early rheumatoid arthritis. His previous medical history including progressive hearing loss for several years and microhematuria for one year attracted our attention. Renal biopsy showed thin basement membrane nephropathy and lymphocytes infiltration of interstitium. To make a precise diagnosis, targeted Next Generation Sequencing (NGS) of an inherited renal disease panel including Alport syndrome genes was performed, which revealed the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Further in silico analyses predicted that the p. Cys451Arg mutation is functionally "damaging", so the diagnosis of Alport syndrome was finally proved. The patient has been receiving the treatment of total glucosides of paeony and leflunomide for rheumatoid arthritis, and Cozaar 50 mg for the protection of kidney so far. During the 10-months follow-up, swelling and tenderness of the joints in this patient had been generally relieved, with no obvious improvement in microhematuria and a slight increase in proteinuria. CONCLUSION: we reported an adult man with the coexistence of rheumatoid arthritis and Alport syndrome with the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Whether the overlap of them is occasional or has a common pathophysiological mechanism is still unclear.

Phenotype variability in a large Spanish family with Alport syndrome associated with novel mutations in COL4A3 gene.

BACKGROUND: Alport syndrome is an inherited renal disorder characterized by glomerular basement membrane lesions with hematuria, proteinuria and frequent hearing defects and ocular abnormalities. The disease is associated with mutations in genes encoding α3, α4, or α5 chains of type IV collagen, namely COL4A3 and COL4A4 in chromosome 2 and COL4A5 in chromosome X. In contrast to the well-known X-linked and autosomal recessive phenotypes, there is very little information about the autosomal dominant. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. METHODS: We investigated a Spanish family with variable phenotype of autosomal dominant Alport syndrome using clinical, histological, and genetic analysis. RESULTS: Mutational analysis of COL4A3 and COL4A4 genes showed a novel heterozygous mutation (c. 998G > A; p.G333E) in exon 18 of the COL4A3 gene. Among relatives carrying the novel mutation, the clinical phenotype was variable. Two additional COL4A3 mutations were found, a Pro-Leu substitution in exon 48 (p.P1461L) and a Ser-Cys substitution in exon 49 (p.S1492C), non-pathogenics alone. CONCLUSION: Carriers of p.G333E and p.P1461L or p.S1492C mutations in COL4A3 gene appear to be more severely affected than carriers of only p.G333E mutation, and the clinical findings has an earlier onset. In this way, we could speculate on a synergistic effect of compound heterozygosity that could explain the different phenotype observed in this family.

Comparison of frequency of asymptomatic microhematuria in patients with stage 2-4 versus stage 0-1 pelvic organ prolapse.

OBJECTIVE: To compare the frequency of asymptomatic microhematuria (AMH) in patients with stage 2-4 and stage 0-1 pelvic organ prolapse (POP). METHODS: The hospital database was searched for women diagnosed with pelvic floor disorders and all medical records were reviewed retrospectively for the presence of AMH. An additional search was conducted for women with other benign gynecological conditions such as myoma uteri, endometrial hyperplasia or adnexal masses without evidence of pelvic organ prolapse (control group). The control group was created using 1:1 matching for age and menopausal status. The frequency of AMH in these patients were compared. The degree of hematuria was categorized as reported by the laboratory as 3 to 25 (low grade hematuria), 26 to 50 (intermediate grade hematuria) and 51 or more (high grade hematuria) red blood cell/high powered field. RESULTS: AMH is statistically significant more often seen in study group than in control group (p:0.016). In the prolapse group 20 women (13.7%) had AMH compared with 9 (6.2%) in the control group. All of 29 patients with AMH had low grade hematuria defined as < 25 red blood cell/high powered field. Patients were followed up for 22 ± 7 (12 to 33) months. No bladder cancer and no cancer of the upper urinary tract has been detected in these 29 patients with AMH during follow-up. CONCLUSIONS: Women with stage 2-4 POP are more likely to be diagnosed with AMH than those with stage 0-1 prolapse.

Potential of an mRNA-Based Urine Assay (Xpert® Bladder Cancer Detection1) in Hematuria Patients - Results from a Cohort Study.

BACKGROUND AND OBJECTIVE: Assessment of patients with hematuria (aH) remains a challenge in urological practice, balancing the benefits of diagnosing a potentially underlying bladder cancer (UCa) against the risks of possibly unnecessary diagnostic interventions. This study analyzes the potential of an mRNA-based urine assay, the Xpert® Bladder Cancer Detection- CE-IVD (Xpert BC-D), in patients with hematuria. MATERIALS AND METHODS: Overall, 368 patients with newly observed painless hematuria and no history of UCa were included in this observational study. Patients received urological workup, including urethrocystoscopy (WLC), upper tract imaging, urine cytology and Xpert BC-D. Patients with positive WLC were recommended to undergo tumor resection (TUR-B). RESULTS: After excluding non-assessable cases, 324 patients were considered for analysis (188 males, 136 females; median age: 61 years). Eight of twenty-eight patients with a positive TUR-B had Ta low grade (LG) tumors; the others were diagnosed with high grade (HG) lesions (Ta: 4, CIS: 2, T1:11, > T1:3). The Xpert BC-D was more sensitive than urine cytology (96% vs. 61%) (p = 0.002). Increased risk ratios (RR) were observed for gross hematuria, gender, urine cytology, and positive Xpert BC-D (all p < 0.05). Age and positive Xpert BC-D remained independent predictors of UCa in multivariate analysis. Simulating a triage with WLC restricted to patients with positive Xpert BC-D could have saved 240 (74.1%) assessments at the cost of missing one pTa LG tumor. CONCLUSIONS: The results suggest a potential role for Xpert BC-D in preselecting patients with hematuria for either further invasive diagnosis or an alternate diagnostic procedure.

Evaluating the Duke Criteria for infectious endocarditis in a single-center retrospective study.

The Duke Criteria have shaped the way infectious endocarditis (IE) is diagnosed in the last 30 years. This study aims to evaluate their current validity and importance in the diagnostic of IE. A retrospective cohort study was conducted on 163 consecutive patients who presented at the University Hospital in Ulm (Germany) with clinical suspicion of IE between 2009 and 2019. With patients' medical records we differentiated between definitive endocarditis (DIE), possible endocarditis (PIE) and rejected endocarditis (RIE) and assessed the validity of the Duke Criteria in comparison to the final discharge diagnosis. We then tried to identify new potential parameters as an addition to the current valid Duke Criteria. The validity of the Duke Criteria improves with the length of hospitalization (especially cardiac imaging criterion, RIE 33.3%, PIE 31.6% and DIE 41.9%, p = 0.622 at admission and RIE 53.3%, PIE 68.4%, DIE 92.2%, p < 0.001 at discharge). At admission, overall sensitivity and specificity were respectively 29.5 and 91.2% in the DIE group. At discharge, sensitivity in the DIE group rose to 77.5% and specificity decreased to 79.4%. Of all screened metrics, microhematuria (p = 0.124), leukocyturia, (p = 0.075), younger age (p = 0.042) and the lack of rheumatoid disease (p = 0.011) showed a difference in incidence (p < 0.2) when comparing DIE and RIE group. In multivariate regression only microhematuria qualified as a potential sixth minor criterion at admission. Even with the latest technological breakthroughs our findings suggest that the Duke Criteria continue to hold value in the accurate assessment of IE. Future efforts must shorten the time until diagnosis.

Comparison of six microscopic methods and two operators for estimation of white and red blood cells in canine urine sediment.

BACKGROUND: Little information is currently available about the analytical variability of urinalysis. OBJECTIVE: We aimed to compare results obtained by two operators using six microscopic methods in the quantification of urinary leukocytes (WBC) and erythrocytes (RBC). METHODS: Forty urine samples (10 mL) were centrifuged (450g, 5 minutes) and resuspended in 0.5 mL of supernatant. Two operators with different expertise in urinalysis interpreted sediment results using the six methods, obtained by combining the use of microscope slides (Slide) or counting chambers (Chamber) with three different techniques: bright-field (BF) microscopy, phase-contrast (PC) microscopy, and stained sediment (SS) evaluations. The mean WBC and RBC counts from 10 fields (Slide) or squares (Chamber) observed at 400× were used to calculate the difference and agreement between operators and methods. We also estimated the concordance between methods in classifying microhematuric or pyuric samples. RESULTS: Operator 2 counted significantly lower WBC counts using Slide+BF (P = 0.009) and Slide+PC (P = 0.001) than Operator 1, whereas no inter-operator differences were recorded for RBC counts. The concordance between the operators ranged from "good" to "very good." No differences or biases were found for WBC counts among the methods, and concordances were "good" to "very good"; proportional biases were found for RBC counts between Slide+BF vs Slide+SS and Slide+PC vs Slide+SS. Concordance measurements for RBC counts ranged from "good" to "very good." CONCLUSIONS: All methods yielded good reproducibility among operators, although stained SS evaluations allowed better identification of WBC by the inexperienced operator. However, we suspected that the SS preparations affected RBC counts. All other methods yielded reproducible WBC and RBC counts.

Microscopic hematuria as a risk factor for IgAN progression: considering this biomarker in selecting and monitoring patients.

Hematuria-either macroscopic hematuria or asymptomatic microscopic hematuria-is a clinical feature typical but not specific for immunoglobulin A nephropathy (IgAN). The only biomarker supported by the Kidney Disease: Improving Global Outcomes group as a predictor of progression, identifying patients needing treatment, is proteinuria >1 g/day persistent despite maximized supportive care. However, proteinuria can occur in the setting of active glomerulonephritis or secondary to sclerotic renal lesions. Microscopic hematuria is observed in experimental models of IgAN after IgA-IgG immunocomplex deposition, activation of inflammation and complement pathways. Oxidative damage, triggered by hemoglobin release, is thought to contribute to the development of proteinuria and progression. Despite being a clinical hallmark of IgAN and having a rational relationship with its pathophysiology, the value of microscopic hematuria in assessing activity and predicting outcomes in patients with IgAN is still debated. This was partly due to a lack of standardization and day-to-day variability of microhematuria, which discouraged the inclusion of microhematuria in large multicenter studies. More recently, several studies from Asia, Europe and the USA have highlighted the importance of microhematuria assessment over longitudinal follow-up, using a systematic approach with either experienced personnel or automated techniques. We report lights and shadows of microhematuria evaluation in IgAN, looking for evidence for a more consistent consensus on its value as a marker of clinical and histological activity, risk assessment and prediction of treatment response. We propose that hematuria should be included as part of the clinical decision-making process when considering when to use immunosuppressive therapy and as part of criteria for enrollment into clinical trials to test drugs targeting the inflammatory reaction elicited by immune pathway activation in IgAN.

Discriminative capacity of guideline recommendations in the assessment of patients with asymptomatic microhematuria.

BACKGROUND & OBJECTIVE: Asymptomatic microhematuria (aMh) remains a diagnostic challenge in urological practice: while aMh is a risk factor of urothelial carcinoma (UC), prevalence of aMh is high. Guidelines were developed to permit risk stratification and reduce diagnostic workload. This study investigates the efficacy of several recommendations. MATERIAL & METHODS: Sixty hundred eight patients with newly diagnosed aMh without previous UC from an academic referral center (A; n = 320) and a private outpatient clinic (B; n = 288) were included. All patients underwent clinical workup including medical history, urine cytology, upper tract imaging and cystoscopy. Eleven former and current guidelines were applied to each patient individually; every patient was classified as either low risk (no further workup recommended) or high risk. Furthermore, a recently developed nomogram for hematuria assessment was included. RESULTS: The cohort comprised 142 females and 466 males (mean age 62 [range 18-92] years). Sixty-one patients (10.0%) were diagnosed with UC. Excluding the Swedish and recent NICE guideline generally advising against urologic workup, application of 9 other recommendations would have diagnosed all UCs and saved 1.6% to 16.1% of patients from workup. For the 2020 US guideline, solely applied to cohort B, 10.6% of patients were classified as low risk. The use of the nomogram would have saved 17.1% to 25% of patients from workup. CONCLUSIONS: Practical relevance of current guidelines is limited as they do not sufficiently identify patients not requiring clinical work up. Thus, guideline adherence may trigger overdiagnosis and even overtreatment. New ways of risk stratification are needed to improve aMh assessment.

Urinary Diagnostic Cytology Beyond the Research of Neoplastic Cells: Usefulness of Erythrocyte Morphology Evaluation to Recognize Microhematuria Source.

Background: Urine cytology is useful to diagnose urinary neoplasms, whereas its role in the study of microhematuria is debatable. Usually, standard urinalysis (dipstick test and sediment examination with bright field microscope) detects the presence of microhematuria, but only urinalysis with phase-contrast microscopy (PCM) (dipstick test and sediment examination with PCM) allows the observation of red blood cell (RBC) morphology and identify their source. Usually glomerular diseases show RBCs with morphological alterations in high percentages, whereas on urologic bleeding, RBCs are rather homogeneous without morphological alterations. Aims: We compare, for the first time, RBC morphology observed in urine cytology and in urinalysis with PCM, to verify whether urinary cytology allows the recognition of the source of bleeding. Methods and Material: A total of 60 patients who had performed both urine cytology and urinalysis with PCM for microhematuria, detected with standard urinalysis, were investigated. Urine cytology showed RBCs and were negative for neoplastic cells or for inflammatory events. Urine samples were processed with the automated method ThinPrep®. RBCs with abnormal and variable shapes were defined as deformed. RBCs of the same spherical shape were defined as non-deformed. Results: Fifty-six urine cytology with RBCs deformed were confirmed in 55 urinalysis with PCM. One case showed RBCs non deformed in urine cytology and in urine sediment. Overall, agreement, between RBC morphology in urine cytology and urinalysis with PCM, was found in 56/60 cases (93%). Conclusions: Therefore, since sediment examination with PCM is available in only few laboratories, we propose that cytopathologist always reports, in urine cytology, any morphological abnormalities of RBCs in order to provide information of the hematuria origin and correctly refer the patient to a nephrologist rather than a urologist.

Phenotyping of a novel COL4A4 and novel GLA variant in a patient presenting with microhematuria and mildly impaired kidney function: a case report.

We describe the case of a 44-year-old male patient with a longstanding history of microhematuria and mildly impaired kidney function (CKD G2A1). The family history disclosed three females who also had microhematuria. Genetic testing by whole exome sequencing revealed two novel variants in COL4A4 (NM_000092.5: c.1181G>T, NP_000083.3: p.Gly394Val, heterozygous, likely pathogenic; Alport syndrome, OMIM# 141200, 203780) and GLA (NM_000169.3: c.460A>G, NP_000160.1: p.Ile154Val, hemizygous, variant of uncertain significance; Fabry disease, OMIM# 301500), respectively. Extensive phenotyping revealed no biochemical or clinical evidence for the presence of Fabry disease. Thus, the GLA c.460A>G, p.Ile154Val, is to be classified as a benign variant, whereas the COL4A4 c.1181G>T, p.Gly394Val confirms the diagnosis of autosomal dominant Alport syndrome in this patient.

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

BACKGROUND: Patients 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. METHODS: A 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 6.9), aligning with the clinical significance of urine pH. RESULTS: Overall, 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. CONCLUSIONS: Approximately 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.

Raman Spectroscopic Detection and Quantification of Macro- and Microhematuria in Human Urine.

Hematuria refers to the presence of blood in urine. Even in small amounts, it may be indicative of disease, ranging from urinary tract infection to cancer. Here, Raman spectroscopy was used to detect and quantify macro- and microhematuria in human urine samples. Anticoagulated whole blood was mixed with freshly collected urine to achieve concentrations of 0, 0.25, 0.5, 1, 2, 6, 10, and 20% blood/urine (v/v). Raman spectra were obtained at 785 nm and data analyzed using chemometric methods and statistical tests with the Rametrix toolboxes for Matlab. Goldindec and iterative smoothing splines with root error adjustment (ISREA) baselining algorithms were used in processing and normalization of Raman spectra. Rametrix was used to apply principal component analysis (PCA), develop discriminate analysis of principal component (DAPC) models, and to validate these models using external leave-one-out cross-validation (LOOCV). Discriminate analysis of principal component models were capable of detecting various levels of microhematuria in unknown urine samples, with prediction accuracies of 91% (using Goldindec spectral baselining) and 94% (using ISREA baselining). Partial least squares regression (PLSR) was then used to estimate/quantify the amount of blood (v/v) in a urine sample, based on its Raman spectrum. Comparing actual and predicted (from Raman spectral computations) hematuria levels, a coefficient of determination (R2) of 0.91 was obtained over all hematuria levels (0-20% v/v), and an R2 of 0.92 was obtained for microhematuria (0-1% v/v) specifically. Overall, the results of this preliminary study suggest that Raman spectroscopy and chemometric analyses can be used to detect and quantify macro- and microhematuria in unprocessed, clinically relevant urine specimens.

Mutation Analysis of Thin Basement Membrane Nephropathy.

Thin basement membrane nephropathy (TBMN) is characterized by the observation of microhematuria and a thin glomerular basement membrane on kidney biopsy specimens. Its main cause is heterozygous mutations of COL4A3 or COL4A4, which also cause late-onset focal segmental glomerulosclerosis (FSGS) or autosomal dominant Alport syndrome (ADAS). Thirteen TBMN cases were analyzed using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and exome sequencing. Ten heterozygous variants were detected in COL4A3 or COL4A4 in nine patients via Sanger sequencing, three of which were novel variants. The diagnostic rate of "likely pathogenic" or "pathogenic" under the American College of Medical Genetics and Genomics guidelines was 53.8% (7 out of 13 patients). There were eight single nucleotide variants, seven of which were glycine substitutions in the collagenous domain, one of which was a splice-site single nucleotide variant, and two of which were deletion variants. One patient had digenic variants in COL4A3 and COL4A4. While MLPA analyses showed negative results, exome sequencing identified three heterozygous variants in causative genes of FSGS in four patients with no apparent variants on Sanger sequencing. Since patients with heterozygous mutations of COL4A3 or COL4A4 showed a wide spectrum of disease from TBMN to ADAS, careful follow-up will be necessary for these patients.