The transcriptome of early compensatory kidney growth reveals cell and time specific responses.

Following kidney removal, the remaining kidney enlarges and increases its function. The mechanism and signals driving this compensatory kidney hypertrophy and the enlargement of its constituent kidney cells remains elusive. RNA-seq studies in mice undergoing hypertrophy 24, 48, and 72 h following nephrectomy were undertaken to understand the early transcriptional changes. This revealed substantial enhancement of cholesterol biosynthesis pathways, increases in mitochondrial gene expression and cell cycle perturbations. Single nuclei RNA-seq delineated cell specific changes at 24 h post nephrectomy and showed that sterol binding protein 2 (SREBP2) activity increases in medullary thick ascending limb cells in keeping with promotion of cholesterol synthesis. Cultured renal tubular cells were examined for insulin-like growth factor-1 (IGF-1) stimulated hypertrophy and SREBP2 was found to be required for increase in cell size. This work describes the early cell specific growth pathways mediating cellular and kidney hypertrophy with an intriguing role for cholesterol synthesis.

Digital health tools in nephrology: A comparative analysis of AI and professional opinions via online polls.

Background: Professional opinion polling has become a popular means of seeking advice for complex nephrology questions in the #AskRenal community on X. ChatGPT is a large language model with remarkable problem-solving capabilities, but its ability to provide solutions for real-world clinical scenarios remains unproven. This study seeks to evaluate how closely ChatGPT's responses align with current prevailing medical opinions in nephrology. Methods: Nephrology polls from X were submitted to ChatGPT-4, which generated answers without prior knowledge of the poll outcomes. Its responses were compared to the poll results (inter-rater) and a second set of responses given after a one-week interval (intra-rater) using Cohen's kappa statistic (κ). Subgroup analysis was performed based on question subject matter. Results: Our analysis comprised two rounds of testing ChatGPT on 271 nephrology-related questions. In the first round, ChatGPT's responses agreed with poll results for 163 of the 271 questions (60.2%; κ = 0.42, 95% CI: 0.38-0.46). In the second round, conducted to assess reproducibility, agreement improved slightly to 171 out of 271 questions (63.1%; κ = 0.46, 95% CI: 0.42-0.50). Comparison of ChatGPT's responses between the two rounds demonstrated high internal consistency, with agreement in 245 out of 271 responses (90.4%; κ = 0.86, 95% CI: 0.82-0.90). Subgroup analysis revealed stronger performance in the combined areas of homeostasis, nephrolithiasis, and pharmacology (κ = 0.53, 95% CI: 0.47-0.59 in both rounds), compared to other nephrology subfields. Conclusion: ChatGPT-4 demonstrates modest capability in replicating prevailing professional opinion in nephrology polls overall, with varying performance levels between question topics and excellent internal consistency. This study provides insights into the potential and limitations of using ChatGPT in medical decision making.

Feasibility and acceptability of the ShareD dEciSIon making for patients with kidney failuRE to improve end-of-life care intervention: A pilot multicentre randomised controlled trial.

Background: Kidney failure is associated with a high disease burden and high mortality rates. National and international guidelines recommend health professionals involve patients with kidney failure in making decisions about end-of-life care, but implementation of these conversations within kidney services varies. We developed the DESIRE (ShareD dEciSIon-making for patients with kidney failuRE to improve end-of-life care) intervention from our studies investigating multiple decision maker needs and experiences of end-of-life care in kidney services. The DESIRE intervention's three components are a training programme for health professionals, a patient decision aid, and a kidney service consultation held to facilitate shared decision-making conversations about planning end-of-life care. Objectives: To assess the feasibility and acceptability of integrating the DESIRE intervention within kidney services. Design: A pilot study using a multicentre randomised controlled design. Setting: Four Danish nephrology departments. Participants: Patients with kidney failure who were 75 years of age or above, their relatives, and health professionals. Methods: Patients were randomised to either the intervention or usual care. Feasibility data regarding delivering the intervention, the trial design, and outcome measures were collected through questionnaires and audio recordings at four points in time: before, during, post, and 3 months after the intervention. Acceptability data were collected through semi-structured interviews with patients and relatives, as well as a focus group with health professionals post the intervention. Results: Twenty-seven patients out of the 32 planned were randomised either to the intervention (n= 14) or usual care (n= 13). In addition, four relatives and 12 health professionals participated. Follow-up was completed by 81 % (n= 22) of patient participants. We found that both feasibility and acceptability data suggested health professionals improved their decision support and shared decision-making skills via the training. Patient and relative participants experienced the intervention as supporting a shared decision-making process; from audio recordings, we showed health professionals were able to support proactively decision-making about end-of-life care within these consultations. All stakeholders perceived the intervention to be effective in promoting shared decision-making and relevant for supporting end-of-life care planning. Conclusions: Participant feedback indicated that the DESIRE intervention can be integrated into practice to support patients, relatives, and health professionals in planning end-of-life care alongside the management of worsening kidney failure. Minimising exhaustion and enhancing engagement with the intervention should be a focus for subsequent refinement of the intervention. Registration: The study has been registered at ClinicalTrials.gov with the identifier: NCT05842772. Date of first recruitment: March 20, 2023.

Monoclonal Gammopathy of Renal Significance With Preexisting Connective Tissue Disease: A Case Report.

Monoclonal gammopathy of renal significance (MGRS) has lately drawn the interest of physicians and pathologists due to the ability of these monoclonal proteins to cause end-organ damage. The early detection of this monoclonal protein along with hematological studies and renal biopsy are essential to establish the associated nephropathological diagnosis. We herein describe the case of a patient with MGRS and the diagnostic entity involved. She responded well to the treatment as co-managed by a multidisciplinary team of nephrologists, hematologists, and renal pathologists.

Increased risk of kidney failure in patients with genetic kidney disorders.

BACKGROUNDIt is unknown whether the risk of kidney disease progression and failure differs between patients with and without genetic kidney disorders.METHODSThree cohorts were evaluated: the prospective Cure Glomerulonephropathy Network (CureGN) and 2 retrospective cohorts from Columbia University, including 5,727 adults and children with kidney disease from any etiology who underwent whole-genome or exome sequencing. The effects of monogenic kidney disorders and APOL1 kidney-risk genotypes on the risk of kidney failure, estimated glomerular filtration rate (eGFR) decline, and disease remission rates were evaluated along with diagnostic yields and the impact of American College of Medical Genetics secondary findings (ACMG SFs).RESULTSMonogenic kidney disorders were identified in 371 patients (6.5%), high-risk APOL1 genotypes in 318 (5.5%), and ACMG SFs in 100 (5.2%). Family history of kidney disease was the strongest predictor of monogenic disorders. After adjustment for traditional risk factors, monogenic kidney disorders were associated with an increased risk of kidney failure (hazard ratio [HR] = 1.72), higher rate of eGFR decline (-3.06 vs. 0.25 mL/min/1.73 m2/year), and lower risk of complete remission (odds ratioNot achieving CR = 5.25). High-risk APOL1 genotypes were associated with an increased risk of kidney failure (HR = 1.67) and faster eGFR decline (-2.28 vs. 0.25 mL/min/1.73 m2), replicating prior findings. ACMG SFs were not associated with personal or family history of associated diseases, but were predicted to impact care in 70% of cases.CONCLUSIONSMonogenic kidney disorders were associated with an increased risk of kidney failure, faster eGFR decline, and lower rates of complete remission, suggesting opportunities for early identification and intervention based on molecular diagnosis.TRIAL REGISTRATIONNA.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases grants U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), U01DK100867 (formerly UM1DK100867), U24DK100845, DK081943, RC2DK116690, 2U01DK100876, 1R01DK136765, 5R01DK082753, and RC2-DK122397; NephCure Kidney International; Department of Defense Research Awards PR201425, W81XWH-16-1-0451, and W81XWH-22-1-0966; National Center for Advancing Translational Sciences grant UL1TR001873; National Library of Medicine grant R01LM013061; National Human Genome Research Institute grant 2U01HG008680.

Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.

Adeno-associated virus (AAV) is a promising in vivo gene delivery platform showing advantages in delivering therapeutic molecules to difficult or undruggable cells. However, natural AAV serotypes have insufficient transduction specificity and efficiency in kidney cells. Here, we developed an evolution-directed selection protocol for renal glomeruli and identified what we believe to be a new vector termed AAV2-GEC that specifically and efficiently targets the glomerular endothelial cells (GEC) after systemic administration and maintains robust GEC tropism in healthy and diseased rodents. AAV2-GEC-mediated delivery of IdeS, a bacterial antibody-cleaving proteinase, provided sustained clearance of kidney-bound antibodies and successfully treated antiglomerular basement membrane glomerulonephritis in mice. Taken together, this study showcases the potential of AAV as a gene delivery platform for challenging cell types. The development of AAV2-GEC and its successful application in the treatment of antibody-mediated kidney disease represents a significant step forward and opens up promising avenues for kidney medicine.

Is there an editorial glass ceiling? Editorial leadership in nephrology and transplantation journals: A gender-based cross-sectional analysis.

AIM: Editors-in-Chief (EiC) play a key role as gatekeepers in academic medicine, often shaping research agendas. Women have historically been underrepresented in editorial leadership roles in academic medicine. The purpose of this study was to examine gender representation among EiC of contemporary transplantation and nephrology journals. METHODS: This cross-sectional study evaluated gender disparities among EiC of transplantation and nephrology medical journals. The study population was drawn from journals in two subject categories (1) 'Transplantation' and (2) 'Urology and Nephrology' in the 2023 Journal Citation Reports. Binary gender classification (woman/man) was determined by the names/pronouns used to describe the EiC on the journal or institutional webpage. The primary outcome was the proportion of women EiC. Secondary outcome was the proportion of women EiC based on journal topic, location and metrics. Descriptive statistics were used. Gender differences were compared using students t-test or Fisher's exact test. RESULTS: A total of 79 EiC were identified of which 16 (20%) were women and 63 (80%) were men (p < .001). Transplantation and nephrology journals had 21% and 20% women EiC, respectively. The proportion of women to men EiC was not impacted by journal category (p = .93), journal location (p = .61), journal impact factor (p = .71) or quartile (p = .59). CONCLUSION: There was a disparity in gender representation in EiC in nephrology and transplantation journals, with men holding 80% of all positions. These findings, among growing evidence of gender disparity, highlight a need for targeted efforts to promote gender equity in academic medicine.

Circadian blood pressure variability and associated factors among chronic kidney disease patients at Nekemte Town public Hospitals, West Oromia, Ethiopia: a comparative cross-sectional study.

OBJECTIVE: This study aimed to assess the pattern of circadian blood pressure variability (CBPV) and associated factors among chronic kidney disease (CKD) patients admitted to Nekemte Town public Hospitals. DESIGN: A hospital-based comparative cross-sectional study was conducted among 130 CKD patients from 01 October to 02 December 2022. Comparisons were performed between the groups using an independent t-test for CBPV (24-hour blood pressure (BP), daytime BP and night-time BP). The dipping pattern was compared by the χ2 test. Multiple logistic regression was used to determine the factors associated with non-dipping patterns in patients with hypertensive CKD (HCKD). SETTING: Two public hospitals in the Nekemte town, Western Ethiopia. PARTICIPANTS: The participants were two independent groups. Group I (HCKD=65) and group II (normotensive CKD (NCKD)=65). RESULTS: The mean 24-hour SD of systolic blood pressure (SBP) was significantly different between HCKD and NCKD patients, 10.17±6.12 mm Hg versus 0.5.4±2.7 mm Hg, respectively (95% CI 0.02 to 1.77, p=0.043). The prevalence of SBP non-dippers was greater among HCKD than NCKD patients (83% vs 63%). Mean 24-hour SBP (95% CI 1.50 (1.15 to 1.96), p=0.003) and estimated glomerular filtration rate (eGFR) (95% CI 2.92 (1.21 to 47.06), p=0.038) were independently associated with non-dipping SBP in HCKD patients. CONCLUSION: Compared with NCKD patients, HCKD patients had significantly greater CBPV. Compared with dippers, non-dippers had a lower mean eGFR.

Interventional nephrology in peritoneal dialysis: Best practice report of the Peritoneal Dialysis Project Group of the Italian Society of Nephrology.

The procedure of peritoneal dialysis (PD) catheter placement is of utmost importance for a good outcome of peritoneal dialysis. Currently, catheters are mainly placed by surgeons and interventional nephrologists. Still, there is a lack of trained personnel in many dialysis units, which can impair the efficiency of PD units and reduce the patients' possibility to enter a PD programme. The Italian Society of Nephrology has endorsed a practical core curriculum for interventional nephrology in PD available on the Society website, which is here reported for the wider nephrology community. The topics addressed are the hernias of the abdominal wall, catheter placement with standard surgical open technique, basic video-laparoscopy, advanced video-laparoscopy, video-laparoscopic cholecystectomy and catheter placement, cuff-shaving and video-laparoscopy in catheter malfunction.

Generating kidney organoids based on developmental nephrology.

Over the past decade, the induction protocols for the two types of kidney organoids (nephron organoids and ureteric bud organoids) from pluripotent stem cells (PSCs) have been established based on the knowledge gained in developmental nephrology. Kidney organoids are now used for disease modeling and drug screening, but they also have potential as tools for clinical transplantation therapy. One of the options to achieve this goal would be to assemble multiple renal progenitor cells (nephron progenitor, ureteric bud, stromal progenitor) to reproduce the organotypic kidney structure from PSCs. At least from mouse PSCs, all the three progenitors have been induced and assembled into such "higher order" kidney organoids. We will provide an overview of the developmental nephrology required for the induction of renal progenitors and discuss recent advances and remaining challenges of kidney organoids for clinical transplantation therapy.

Immune checkpoint inhibitor-associated nephritis - treatment standard.

Over the last 13 years, the use of immune checkpoint inhibitor (ICI) therapy has grown remarkably, owing to their unprecedented anti-tumor efficacy in certain tumor groups. With increased use of ICIs, we are seeing immune-related adverse events (irAE's) more frequently. Renal irAE's, such as ICI-associated acute kidney injury (ICI-AKI), are reported in 2-5% of patients treated with ICIs, with acute tubulointerstitial nephritis (ATIN) as the most common histopathologic lesion, though various forms of glomerulonephritis have also been reported. Modifiable risk factors for ICI-AKI include concurrent use of ATIN-associated drugs, like proton pump inhibitors, non-steroidal anti-inflammatory drugs and antibiotics, and dual ICI therapy with both CTLA-4 and PD1/PDL-1 blockade. Kidney biopsies remain the diagnostic modality of choice, though several promising non-invasive biomarkers, which have not yet been broadly clinically validated have emerged. The treatment of ICI-AKI involves holding ICIs, discontinuation of ATIN-associated drugs, and initiation of immunosuppression with corticosteroids as first-line therapy. With prompt treatment initiation, most patients achieve full or partial renal recovery, allowing for re-challenge with ICI. However, a subset of patients will require additional steroid-sparing therapies for corticosteroid-dependent or refractory ICI-AKI. Here we review developments in our understanding of the pathophysiology of ICI-AKI, the approach to diagnosis (with a focus on the emergence of novel diagnostic tools), prognostic factors and the current evidence for establishing treatment standards for ICI-AKI. As the evidence base remains largely retrospective, we identify questions that would benefit from future prospective studies in the diagnosis, management, and prognostication of ICI-AKI.

Interventions to support young adults and families with the healthcare transition between paediatric and adult nephrology health services: A systematic scoping review.

BACKGROUND: Healthcare transition can be challenging for young people and families living with chronic kidney conditions, including those with rare renal disorders who often have multi-systemic conditions, those who have undergone kidney transplantation, and those who face intense treatments like dialysis. Comprehensive, holistic healthcare transition interventions are required, encompassing physical, psychosocial, sexual, educational and vocational support. AIM: This manuscript presents a systematic scoping review synthesising the healthcare transition interventions to support youth and families within nephrology services. METHODS: This review followed Arksey and O'Malley's five-stage framework, updated by Levac, Colquhoun and O'Brien and the Joanna Briggs Institute. Six databases were systematically searched: CINAHL Plus with Full Text, Embase, PsycINFO, Web of Science, PubMed, and the Applied Social Sciences Index and Abstracts (ASSIA), locating 12,662 records. Following a systematic screening process, 28 articles met the inclusion criteria. Results were analysed systematically and presented using the PAGER framework developed by Bradbury-Jones et al. (2022). RESULTS: Various interventions were sourced. Three broad patterns emerged: 1. Contextual Factors, e.g. cultural differences between paediatric and adult services; 2. Major Intervention Components, e.g. parental/familial/peer-to-peer support, and 3. Personal factors, e.g., self-management ability. CONCLUSION: Few interventions are available to support youth with rare renal disorders, specifically. Future research must be directed at this cohort. Healthcare transition timing remains hotly contested, with additional guidance required to support decision-making. Finally, limited interventions have been evaluated for practice. IMPLICATIONS: This review has provided various considerations/recommendations that should be taken into account when designing, implementing or evaluating future healthcare transition supports.

Diagnostic performance of an albuminuria point-of-care test in screening for chronic kidney disease among young people living with HIV in Uganda: a cross-sectional study.

OBJECTIVES: The main aim was to determine the diagnostic performance of an albuminuria point-of-care test (POC) for diagnosis of chronic kidney disease among young people living with HIV (YPLHIV) in Uganda. DESIGN: We conducted a cross-sectional study comparing the diagnostic performance of MicroalbuPHAN (Erba Lachema, Czech Republic), an albuminuria POC test against the laboratory-measured albumin and creatinine as the reference standard. SETTING: The study was set in seven HIV clinics in Kampala, Uganda that provide antiretroviral therapy to adults and children living with HIV. The study took place from April to August 2023. PARTICIPANTS: 497 YPLHIV aged 10-24 years who were diagnosed with HIV before 10 years of age were randomly selected from the HIV clinics. Pregnant YPLHIV were excluded. PROCEDURES: Participants provided a spot urine sample that was tested for albumin and creatinine using the POC and in the laboratory and proteinuria using urine dipstick. The sensitivity, specificity, negative and positive predictive values (NPV, PPV) of the POC versus the laboratory test were calculated, and factors associated with having a positive POC test were estimated using logistic regression. OUTCOME MEASURES: The primary outcome was a diagnosis of albuminuria defined as an albumin creatinine ratio above 30 mg/g. RESULTS: Of the 497 participants enrolled, 278 (55.9%) were female and 331 (66.8%) were aged 10-17 years. The POC test had a sensitivity of 74.5% (95% CI 70.6% to 78.4%) and specificity of 68.1% (95% CI 63.9% to 72.3%). The PPV was 21.5% (95% CI 17.8% to 25.1%) and the NPV was 95.8% (95% CI 94.0% to 97.6%), with an accuracy of 68.8%. There was strong evidence that a positive POC test was associated with having proteinuria (OR 2.82; 95% CI 1.89 to 4.22, p<0.001); body mass index <19.5 (OR 1.69 95% CI 1.17 to 2.45, p=0.005) and being male (OR 1.48; 95% CI 1.02 to 2.14, p=0.04). CONCLUSIONS: The albuminuria POC test had low sensitivity and specificity. However, it can be used to exclude kidney disease given its high NPV. It should be validated against the 24-hour urinary excretion rate to further determine its diagnostic performance.

New triple therapy for the diagnosis of CKD-MBD: a cross-sectional study in Shanxi province.

OBJECTIVES: To seek a triple combination of biomarkers for early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and to explore the diagnostic efficacy of ß2-microglobulin, parathyroid hormone and blood urea nitrogen in chronic kidney disease-mineral and bone metabolic disorder. PARTICIPANTS: We collected medical records of 864 patients with chronic kidney disease (without direct contact with patients) and divided them into two groups based on the renal bone disease manifestations of all patients. PRIMARY AND SECONDARY OUTCOME MEASURES: There were 148 and 716 subjects in the Chronic kidney disease-mineral and bone metabolic disorder and the control groups, respectively. The aggregated data included basic information and various clinical laboratory indicators, such as blood lipid profile, antibody and electrolyte levels, along with renal function-related indicators. RESULTS: It was observed that most renal osteopathy occurs in the later stages of chronic kidney disease. In the comparison of two clinical laboratory indicators, 16 factors were selected for curve analysis and compared. We discovered that factors with high diagnostic values were ß2-microglobulin, parathyroid hormone and blood urea nitrogen. CONCLUSIONS: The triple combination of ß2-microglobulin+parathyroid hormone+blood urea nitrogen indicators can play the crucial role of a sensitive indicator for the early diagnosis of chronic kidney disease-mineral and bone metabolic disorder and in preventing or delaying the progress of chronic kidney disease-mineral and bone metabolic disorder.

Severe Granulomatosis With Polyangiitis Treated With Low-Dose Cyclophosphamide, Rituximab, Glucocorticoids, and Plasma Exchange: A Case Report.

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis that affects blood vessels and presents with vague constitutional symptoms, but more serious manifestations can develop, including pulmonary complications and glomerulonephritis. Currently, there are no definitive treatment guidelines. We present a case of a 66-year-old male with no previous medical history who was admitted for generalized constitutional symptoms for the past month. Imaging of the patient's brain revealed dural enhancement. Bronchoalveolar lavage was done and revealed diffuse alveolar hemorrhage (DAH). A kidney biopsy revealed granulomatosis with polyangiitis. The patient's hospital course was complicated by acute renal failure and required hemodialysis. Due to the patient's multi-organ involvement, the patient was treated aggressively with cyclophosphamide, rituximab, plasma exchange (PE), and steroids. GPA is a systemic vasculitis that can present with multi-organ involvement. A prompt diagnosis is necessary to initiate treatment and preserve organ function. More research is needed to determine which combination therapies are the best treatment modalities in cases of severe multi-organ system involvement.

Basal knowledge in the field of pediatric nephrology and its enhancement following specific training of ChatGPT-4 "omni" and Gemini 1.5 Flash.

BACKGROUND: We aimed to evaluate the baseline performance and improvement of ChatGPT-4 "omni" (ChatGPT-4o) and Gemini 1.5 Flash (Gemini 1.5) in answering multiple-choice questions related to pediatric nephrology after specific training. METHODS: Using questions from the "Educational Review" articles published by Pediatric Nephrology between January 2014 and April 2024, the models were tested both before and after specific training with Portable Data Format (PDF) and text (TXT) file formats of the Educational Review articles removing the last page containing the correct answers using a Python script. The number of correct answers was recorded. RESULTS: Before training, ChatGPT-4o correctly answered 75.2% of the 1395 questions, outperforming Gemini 1.5, which answered 64.9% correctly (p < 0.001). After training with PDF files, ChatGPT-4o's accuracy increased to 77.8%, while Gemini 1.5 improved significantly to 84.7% (p < 0.001). Training with TXT files showed similar results, with ChatGPT-4o maintaining 77.8% accuracy and Gemini 1.5 further improving to 87.6% (p < 0.001). CONCLUSIONS: The study highlights that while ChatGPT-4o has strong baseline performance, specific training does not significantly enhance its accuracy. Conversely, Gemini 1.5, despite its lower initial performance, shows substantial improvement with training, particularly with TXT files. These findings suggest Gemini 1.5's superior ability to store and retrieve information, making it potentially more effective in clinical applications, albeit with a dependency on additional data for optimal performance.

Artificial Intelligence and Machine Learning in Predicting Intradialytic Hypotension in Hemodialysis Patients: A Systematic Review.

Intradialytic hypotension (IDH) is a common and potentially life-threatening complication in hemodialysis patients. Traditional preventive measures have shown limited effectiveness in reducing IDH incidence. This systematic review evaluates the existing literature on the use of artificial intelligence (AI) and machine learning (ML) models for predicting IDH in hemodialysis patients. A comprehensive literature search identified five eligible studies employing diverse AI/ML algorithms, including artificial neural networks, decision trees, support vector machines, XGBoost, random forests, and LightGBM. These models utilized various features such as patient demographics, clinical data, laboratory findings, and dialysis-related parameters. The studies reported promising results, with several models achieving high prediction accuracies, sensitivities, specificities, and area under the receiver operating characteristic curve values for predicting IDH. However, limitations include variations in study populations, retrospective designs, and the need for prospective validation. Future research should focus on multicenter prospective studies, assessing clinical utility, and integrating interpretable AI/ML models into clinical decision support systems.

A variant of unknown significance in the COL4A5 gene-related renal disease: A novel case report.

In this case report, we report our findings of a variant of uncertain significance in the COL4A5 gene in four family members. Patient 0 is a 16-year-old female with no prior medical history referred to Pediatric Nephrology for the evaluation of microscopic hematuria. Upon further investigation, she was found to have a family history of both microscopic hematuria and kidney disease, prompting genetic testing and intimation of a possible cause and inheritance pattern for kidney disease and hematuria in the COL4A5 gene.