An enhanced machine learning approach for effective prediction of IgA nephropathy patients with severe proteinuria based on clinical data.

IgA Nephropathy (IgAN) is a disease of the glomeruli that may eventually lead to chronic kidney disease or kidney failure. The signs and symptoms of IgAN nephropathy are usually not specific enough and are similar to those of other glomerular or inflammatory diseases. This makes a correct diagnosis more difficult. This study collected data from a sample of adult patients diagnosed with primary IgAN at the First Affiliated Hospital of Wenzhou Medical University, with proteinuria ≥1 g/d at the time of diagnosis. Based on these samples, we propose a machine learning framework based on weIghted meaN oF vectOrs (INFO). An enhanced COINFO algorithm is proposed by merging INFO, Cauchy Mutation (CM) and Oppositional-based Learning (OBL) strategies. At the same time, COINFO and Support Vector Machine (SVM) were integrated to construct the BCOINFO-SVM framework for IgAN diagnosis and prediction. Initially, the proposed enhanced COINFO is evaluated using the IEEE CEC2017 benchmark problems, with the outcomes demonstrating its efficient optimization capability and accuracy in convergence. Furthermore, the feature selection capability of the proposed method is verified on the public medical datasets. Finally, the auxiliary diagnostic experiment was carried out through IgAN real sample data. The results demonstrate that the proposed BCOINFO-SVM can screen out essential features such as High-Density Lipoprotein (HDL), Uric Acid (UA), Cardiovascular Disease (CVD), Hypertension and Diabetes. Simultaneously, the BCOINFO-SVM model achieves an accuracy of 98.56%, with sensitivity at 96.08% and specificity at 97.73%, making it a potential auxiliary diagnostic model for IgAN.

Admission proteinuria predicts the incidence of acute kidney injury among patients with acute ST-segment elevation myocardial infarction: a retrospective cohort study.

BACKGROUND: Proteinuria indicates renal dysfunction and is associated with the development of acute kidney injury (AKI) in several conditions, but the association between proteinuria and AKI in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. This research aims to investigate the predictive value of proteinuria for the development of AKI in STEMI patients. METHODS: A total of 2735 STEMI patients were enrolled. The present study's endpoint was AKI incidence during hospitalization. AKI is defined according to the Kidney Disease: Improving Global Outcomes criteria. We defined proteinuria, measured with a dipstick, as mild (1+) or heavy (2+ to 4+). Multivariate logistic regression and subgroup analyses were used to testify to the association between proteinuria and AKI. RESULTS: Overall, proteinuria was observed in 634 (23.2%) patients. Multivariate logistic regression analyses revealed that proteinuria [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.25-2.00; P  < 0.001] was the independent predictive factor for AKI. Severe proteinuria was associated with a higher adjusted risk for AKI compared with the nonproteinuria group (mild proteinuria: OR, 1.35; 95% CI, 1.04-1.75; P  = 0.025; severe proteinuria: OR, 2.50; 95% CI, 1.70-3.68; P  < 0.001). The association was highly consistent across all studied subgroups. (all P for interaction >0.05). CONCLUSION: Admission proteinuria measured using a urine dipstick is an independent risk factor for the development of AKI in STEMI patients.

Population characteristics and diagnosis rate of chronic kidney disease by eGFR and proteinuria in Japanese clinical practice: an observational database study.

Chronic kidney disease (CKD) guidelines recommend early identification and intervention to delay the progression of CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) heatmap is widely used for risk evaluation in CKD management; however, real-world evidence on clinical characteristics based on the KDIGO heatmap remains limited worldwide including Japan. In order to understand the management of CKD including its diagnostic rates in a Japanese clinical setting on the basis of KDIGO heatmap, we utilized a medical record database that contains estimated glomerular filtration rate (eGFR) and urine protein data. Adult individuals (≥ 18 years) with two eGFR results of < 90 mL/min/1.73 m2, 90-360 days apart, were included. Approximately half of patients (452,996/788,059) had proteinuria test results and 6.9% (54,073) had quantitative results. CKD diagnosis rate in patients without proteinuria data was 5.9%, with a lower rate (2.9%) in stage G2; the corresponding rates with quantitative test results were 43.5% and 31.3%, respectively. The most frequent comorbidities were hypertension, diabetes, and cardiovascular disease, and their prevalence increased as the eGFR and proteinuria stages progressed. This study revealed a low rate of proteinuria assessment, especially using quantitative methods, and diagnosis in individuals with suspected CKD. With emerging treatment options to prevent CKD progression and complication onset, there is a need for early evaluation and diagnosis of CKD.

Development of a Quantitative Digital Urinalysis Tool for Detection of Nitrite, Protein, Creatinine, and pH.

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25-200 µM), protein (2-1024 mg/dL), creatinine (2-1024 mg/dL), and pH (5.0-8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter's secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.

Evaluation of a urine dipstick protein to urine specific gravity ratio for the detection of proteinuria in dogs and cats.

BACKGROUND: The utility of urine dipsticks for the quantification of proteinuria is limited because of the influence of urine specific gravity (USG). To circumvent the need for urine protein creatinine ratios (UPCR) some have proposed a calculated dipstick urine protein to USG ratio (DUR) for the detection of proteinuria. However, the performance of DUR has not been evaluated in veterinary patients. OBJECTIVES: Evaluate the correlation between DUR and UPCR, while also assessing the effect of urine characteristics on this relationship and evaluating the performance of DUR in detecting proteinuria. ANIMALS: Urine samples from 308 dogs and 70 cats. METHODS: Retrospective cohort study of urinalyses and UPCRs from dogs and cats collected between 2016 and 2021. RESULTS: Both canine and feline urine samples showed a positive moderate correlation between the UPCR and DUR. The correlation was not influenced by the presence of active urine sediment, glucosuria, or urine pH. In detecting canine urine samples with a UPCR >0.5, an optimal DUR of 1.4 had sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 89%, 83%, 96%, and 63%, respectively. In detecting feline urine samples with a UPCR >0.4, an optimal DUR of 2.1 had sensitivity, specificity, PPV, and NPV of 70%, 100%, 100%, and 75%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of the DUR can be a relatively reliable method for identification of proteinuria. However, given its poor NPV, the DUR cannot be recommended for exclusion of proteinuric patients.

Diagnostic value of renal biopsy in anti-phospholipase A2 receptor antibody-positive patients with proteinuria in China.

Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with "full house" and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Fractional excretion of total protein in patients with nephrotic syndrome.

BACKGROUND: The urine protein to creatinine ratio (UPCR) correlates well with the 24-h urine protein test (24-h UPT) and is a reliable indicator of proteinuria. However, in nephrotic syndrome, the correlation between the UPCR and the 24-h UPT tends to decrease. To address this, we introduced the fractional excretion of total protein (FETP), which reflects serum total protein and creatinine levels because severe hypoproteinemia and/or elevated serum creatinine levels tend to occur under these conditions. The 24-h UPT corrected for body surface area (BSA) (24-h UPT/BSA) was used to take body size into consideration. The correlation coefficients for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR were calculated. The statistical significance of the differences between these coefficients was also calculated. METHODS: Thirty-six pediatric patients with nephrotic syndrome were included in this study. The FETP was calculated as total protein clearance/creatinine clearance (%). Correlation coefficients were calculated for 24-h UPT/BSA and FETP and 24-h UPT/BSA and UPCR. The statistical significance of the differences between these coefficients was also calculated. RESULTS: The mean ± standard error of FETP was 0.11% ± 0.013%. The correlation coefficients of FETP and UPCR with 24-h UPT/BSA were 0.91 and 0.81, respectively. The FETP demonstrated a significantly stronger correlation with 24-h UPT/BSA than with UPCR (p = 0.01). CONCLUSIONS: The FETP correlated more strongly with 24-h UPT/BSA than with UPCR in patients with nephrotic syndrome. The FETP is a reliable indicator of proteinuria in nephrotic syndrome, especially in patients with severe hypoproteinemia or elevated serum creatinine levels.

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations.

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30-100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

Early-Stage Chronic Kidney Disease and Related Health Care Spending.

Importance: The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective: To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants: Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure: The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. Main Outcome and Measures: The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results: Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance: In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

The diagnostic Accuracy of Visual versus automated dipstick proteinuria testing in Pregnancy: A systematic review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE and EMBASE databases were searched from inception to 13 November 2020. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Included studies measured the sensitivity and specificity ofPOC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determinedheterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within thesubgroupstest brand, reference standard, and hypertension status. RESULTS: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively. CONCLUSION: Visual dipsticks have comparable accuracy to automated readers, yet are notadequate as a rule-out test for proteinuria. Proteinuria POC testing maybe beneficial inantenatal care when repeatfollow-up tests are performed. PROSPERO Registration Number: CRD42021231914.

Plasma neutrophil gelatinase-associated lipocalin predicts renal tubulointerstitial injury in patients with IgA nephropathy.

OBJECTIVE: To investigate the relationship of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) with clinical indicators and pathology in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: Clinical and pathological data of 36 patients with primary IgAN diagnosed by kidney biopsy were selected. The Oxford and Lee classifications were used to rank the pathology of IgAN patients and the particle-enhanced immunoturbidimetric method was adopted to measure pNGAL and uNGAL. Subsequently, the correlations of pNGAL and uNGAL levels with clinical indices and pathology were analyzed to evaluate the diagnostic value. RESULTS: Referring to the comparison group, pNGAL levels were elevated in the women, 24-hour proteinuria ≥ 1 g/day, Lee classification IV - V, and tubular atrophy/interstitial fibrosis (T) score of 1 subgroup of Oxford classification (p < 0.05). The pNGAL was positively correlated with 24-hour proteinuria, urine microalbumin, urine α1 microglobulin, and the score of T (p < 0.05), while uNGAL was negatively correlated with serum albumin (p < 0.05). The occurrence of T1 was evaluated by pNGAL, serum creatinine (Scr), 24-hour proteinuria, and estimated glomerular filtration rate (eGFR), and it was shown that the area under the curve of 24-hour proteinuria, pNGAL, Scr, and eGFR were 0.629, 0.817, 0.919, and 0.799, respectively; in addition, the sensitivity of both pNGAL and eGFR are 100%. CONCLUSION: The pNGAL levels in patients with IgAN are positively correlated with the Lee and Oxford classifications of T scores. The level of pNGAL in IgAN patients is found to be a prominent indicator for identification of renal tubulointerstitial injury and perhaps this feature may make it a non-invasive predictor for progression of IgAN.

IgA nephropathy in children: before and after the start of COVID-19.

BACKGROUND: We describe the clinical course of children with IgA nephropathy (IgAN), diagnosed before and after the emergence of COVID-19. We hypothesized that COVID-19 vaccination and/or infection resulted in more children with IgAN to present clinically. METHODS: We conducted a retrospective cohort study of children with IgAN diagnosed on kidney biopsy from 2014-2020 (Period 1) and 2021-2022 (Period 2). Baseline characteristics, clinical presentation, investigations and treatments were compared between patients diagnosed in Period 1 and Period 2, as well as between patients with and without chronic changes on kidney biopsy. Continuous variables were compared using the Wilcoxon rank sum test. Categorical variables were compared using χ2 or Fisher exact tests. RESULTS: Nineteen children with IgAN were diagnosed by kidney biopsy, with 10 during Period 1 and 9 patients during Period 2 (an average of 1-2 patients/year and 4-5 patients/year in Periods 1 and 2, respectively). The most common indication for kidney biopsy is proteinuria with urine protein/creatinine ratio 1.4 (interquartile range [IQR] 1.2-9.0) vs. 0.8 (IQR 0.6-1.5) g/g (p = 0.064) at time of kidney biopsy for patients in Period 1 and 2, respectively. Clinical course was similar in both periods. No patient required acute or chronic kidney replacement therapy. CONCLUSIONS: The rate of diagnosing children with IgAN was higher since the emergence of COVID-19, suggesting that COVID-19 may trigger an immune response responsible for IgAN, similar to other mucosal infections.

Proteinuria selectivity index in renal disease.

One of the main barriers to early detection and subsequent prevention of kidney diseases is the accessibility and feasibility of testing, especially in urine research. The proteinuria selectivity index (PSI or SI) is a method used to assess changes in glomerular permeability in glomerular diseases. It describes the pattern of proteinuria by comparing the clearance rates of large molecular proteins and transferrin, categorizing it as selective or non-selective. PSI is widely applied for kidney disease classification, prediction of corticosteroid efficacy, and prognosis. Herein, we reviewed the clinical applications and recent advancements of PSI in glomerular diseases, compared it with commonly used renal function biomarkers, and discussed the future research directions for PSI as a potential predictive marker for response to specific biologics.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Nutcracker syndrome in pediatrics: initial findings and long-term follow-up results.

BACKGROUND: Nutcracker syndrome (NCS) describes a set of symptoms and signs resulting from compression of the left renal vein (LRV). There is a lack of knowledge about its natural course, diagnosis, and management, especially in children. Herein, we present our single-center experience with a large number of patients who have long-term follow-up results. METHODS: All patients with NCS diagnosed between January 2011 and March 2021 were included and their data were obtained retrospectively. RESULTS: A total of 123 NCS patients (85 females) were included. The median age at the time of diagnosis was 12 (IQR 10-14) years, and BMI percentiles were below 5% in 38% of the cases. At the time of diagnosis, two-thirds of the patients were asymptomatic. The most common laboratory finding was nephritic proteinuria (98%), followed by microscopic hematuria (16%). Signs of LRV compression were significantly more evident in upright position Doppler ultrasonography (DUS) examination. All patients have been followed conservatively; hematuria and/or proteinuria resolved in 43 of the 108 patients (40%) within 35.8 ± 25.8 months of follow-up. Control DUS was performed in 52 patients after a mean period of 39.1 ± 21.3 months. The median peak velocity and diameter ratios of the LRV in the upright position were found to be decreased significantly when compared to the initial assessment (p < 0.05). Normal DUS findings were noted in 13 patients at the final evaluation. CONCLUSIONS: In unexplained proteinuria and/or hematuria, NCS should be considered, especially in asthenic adolescents. Our results support conservative management in children as the first-line treatment approach.

[Macrohematuria in children and adolescents]. / Makrohämaturie im Kindes- und Jugendalter.

Hematuria is usually only noticed early in the case of macrohematuria. In around half of affected children, macrohematuria is caused by a urinary tract infection. In all other cases, a careful diagnosis is required. In addition to a detailed medical history, this builds upon a precise examination of the urine (microscopy, quantitative determination of proteinuria [mg albumin/g creatinine in spontaneously voided urine]) and measurement of blood pressure. The work-up usually includes sonography as the primary imaging modality. Invasive diagnostic tests using cystoscopy are only necessary in exceptional cases. If there is evidence of glomerulonephritis, a kidney biopsy may be indicated. Careful attention should be given to persisting microhematuria (> 6 months) and Alport syndrome should be confirmed or ruled out. Heterozygotic Alport syndrome can also be a possible cause of chronic renal failure.