Persistent Hematuria Research Articles

A Rare Case of Acute Promyelocytic Leukemia with Concomitant PML-RARA Fusion and TP53 Loss/ider(17)(q10)t(15;17) Showing Complete Clinical and Molecular response: A Case Report

Abstract Introduction/Objective To report a case with rare cytogenetic abnormality: a patient with newly diagnosed acute promyelocytic leukemia (APL) with cytogenetic findings of t(15;17)(q24;q21), trisomy 8 and ider(17)(q10)t(15;17)-TP53 loss. The presence of isochromosome 17q may indicate the possibility of an unfavorable outcome. However, the case showed complete clinical and molecular response. Methods/Case Report A case of a 53-year-old female with history of ITP post-splenectomy presented with persistent hematuria, easy bruising, and worsening fatigue. She had mild microcytic anemia, moderate thrombocytopenia, 3% promyelocytes, and 14% blasts on differential CBC count. With increased PT, PTT, LDH, Uric acid and decreased fibrinogen level, APL was clinically suspected. The patient was initiated on all-trans retinoic acid (ATRA), allopurinol, and IV fluids. Bone marrow (BM) biopsy confirmed the diagnosis with unusual cytogenetic findings. The patient underwent induction and consolidation therapies (4 weeks each) with ATRA plus Arsenic Trioxide (ATO) and followed- up with a series of marrow biopsies, cytogenetic and molecular studies. Results (if a Case Study enter NA) The patient demonstrated complete clinical, histological, and molecular response. She tolerated the treatment without major side effects, showing improvement in CBC counts, coagulation profile and tumor lysis labs. Initial BM exam revealed hypercellularity with infiltrating sheets of atypical hypergranular promyelocytes (~80%) and minimal residual left trilineage hematopoiesis. Flow cytometry revealed a CD34 negative, CD117 variable abnormal promyelocyte population (~67% of total events). FISH was positive for PML/RARA translocation (15; 17) and TP53 loss. Karyotype showed 46,XX,der(15)t(15;17)(q24;q21),ider(17)(q10)t(15;17)[12]/47,idem,+8[9]. By the end of treatment, BM biopsy was normocellular with trilineage hematopoiesis and no definitive evidence of acute leukemia or increase in blasts. The Karyotype was normal. Quantitative PCR for PML-RARA was negative, indicating complete molecular remission. Conclusion In this unique case of APL with unusual cytogenetic abnormalities the literature demonstrates controversial data. The patient achieved complete clinical and molecular remission following standard treatment. This may indicate the limited prognostic significance of these additional cytogenetic abnormalities in this case.

Detection of Alport gene variants in children and young people with persistent haematuria.

Genetic kidney disease is an important cause of persistent microscopic haematuria in children and young people. We aimed to determine the frequency of variants in the Alport syndrome genes (COL4A3, COL4A4 or COL4A5) in individuals under 18 years of age presenting with persistent microscopic haematuria to a single specialist centre in the UK over a 10-year period. We conducted a retrospective longitudinal study of individuals referred to a tertiary paediatric nephrology service with persistent microscopic haematuria between April 2012 to 2022. A total of 224 individuals (female 51.8%) were evaluated with persistent microscopic haematuria of greater than 6 months duration. The age at presentation was 7.5 ± 4.3 years (mean ± SD) with a duration of follow-up of 6.8 ± 4.6 years (mean ± SD). Targeted exome sequencing was performed in 134 individuals and 91 (68%) had a pathogenic or likely pathogenic variant in COL4A3, COL4A4 or COL4A5. Only 49.5% of individuals with identified variants had a family history of microscopic haematuria documented and 37.4% (34/91) had additional proteinuria at presentation. COL4A5 was the most common gene affected and missense variants affecting glycine residues were the most common variant type. Over two-thirds of children and young people who underwent genetic testing had an identifiable genetic basis for their microscopic haematuria and over half did not have a documented family history. Genetic testing should be part of the evaluation of persistent microscopic haematuria despite a negative family history.

A comprehensive review of Alport syndrome: definition, pathophysiology, clinical manifestations, and diagnostic considerations.

Alport syndrome, a rare genetic disorder affecting around 1 in 50,000 individuals, primarily presents as microscopic hematuria and chronic kidney disease (CKD) with associated extrarenal complications. The Alport syndrome results from mutations in COL4A3, COL4A4, and COL4A5 genes, disrupting the formation of the α3-α4-α5 chain in the collagen IV network. The etiology involves X chromosome-related, autosomal dominant, autosomal recessive, and digenic inheritance patterns. The disease primarily manifests as kidney involvement, featuring persistent hematuria, proteinuria, and a progressive decline in renal function. Hearing loss, ocular abnormalities, and extrarenal manifestations further contribute to its complexity. Genotype-phenotype correlations are relatively evident, with distinct presentations in X-linked, autosomal recessive, and autosomal dominant cases. Diagnosis relies on urinalysis, histologic examination, and genetic testing with advancements in next-generation sequencing aiding identification. Although no specific treatment exists, early diagnosis improves outcomes, emphasizing the importance of genetic testing for prognosis and familial screening. The purpose of this review is to advance knowledge and enhance understanding of Alport syndrome.

EP118 - Chronic Vesicouterine Fistula (Youssef's syndrome) Complete Opening of Anterior Uterine Wall in the Urinary Bladder: A- very rare case

Abstract Background Vesicouterine fistula is an uncommon urogenital condition typically following Caesarean sections (C/S). Youssef syndrome, characterized by haematuria, amenorrhea, and urinary incontinence, poses a diagnostic challenge and demands comprehensive assessment. Case report We present a case of a 40-year-old woman with persistent urine incontinence and haematuria for three years post her fourth C/S. Clinical evaluation revealed periodic lower abdominal pain, haematuria, amenorrhea, and urine incontinence. sonography was normally reported, while cystoscopy revealed a complete 5x2 cm opening between the anterior uterine wall and the posterior bladder wall, confirming Youssef syndrome. After a course of antibiotic therapy, surgical intervention was planned. Transabdominal total hysterectomy, partial cystectomy, and repair were performed following meticulous anatomical delineation using cystoscopy. The procedure involved dissecting the vesicouterine attachment, performing partial cystectomy, and eventually total hysterectomy. Closure of the urinary bladder defect with absorbable sutures and a negative leak test concluded the surgery. The patient showed no postoperative complications, with follow-ups at 6 and 12 months indicating complete recovery without complaints.

Clinical evolution of bladder carcinosarcoma: A case report and literature review.

Bladder carcinosarcoma (BC) is a malignant tumor composed of a mixture of malignant epithelial and stromal components. Carcinosarcoma mostly occurs in the upper respiratory tract and upper gastrointestinal tract and is less common in the urinary system. The incidence of malignant tumors of the urinary system is <3%. It rarely occurs in the bladder and accounts for approximately 0.31% of all malignant bladder tumors. A literature review and this report will help to further improve our understanding, diagnosis, and treatment of bladder carcinosarcoma (BC). We describe the case of an 80-year-old female patient who was admitted to the hospital with a history of intermittent hematuria for 3 years. Furthermore, total cystectomy was refused when a BC was diagnosed. Palliative resection surgery was necessary because of the recurrent hematuria and abdominal pain. Pathologically confirmed BC after surgery. The patient's first transurethral resection of bladder tumor (TURBT) was diagnosed as BC. However, the patient refused a total cystectomy. Two months after intravesical treatment with epirubicin, bladder tumor recurrence was observed during follow-up cystoscopy. The patient underwent a second TURBT for hemostatic treatment due to persistent hematuria. Due to hematuria and abdominal pain, a third TURBT was performed to reduce tumor size and stop bleeding. Finally, tumor recurrence resulted in bilateral hydronephrosis, and the patient underwent bilateral renal catheter drainage guided by B-ultrasound. Bladder carcinosarcoma caused uremia, electrolyte imbalance, and sepsis. Approximately 19 months after the discovery of the tumor, the patient died. Radical bladder resection is recommended once a BC is diagnosed. By reporting the cases and reviewing the literature in the database, we will summarize the epidemiology, origin, etiology, clinical features, existing treatments, and prognostic factors of BC, and propose new prospects for BC therapy.

Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome

BackgroundAlport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient.MethodsWe screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R).ResultsWe identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same.ConclusionsOur research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.

Study of steroid-resistant nephrotic syndrome: a single center experience

BackgroundNephrotic syndrome (NS) is a disease with favorable outcomes in most cases. Failure to respond to steroids is one of the most important predictors of clinical outcome. We performed a retrospective study on 51 primary idiopathic SRNS cases presenting between January 2011 and June 2021 at Alexandria University Children’s Hospital (AUCH) by retrieving data from their clinic files. Cases with secondary causes of NS or suspected genetic causes were excluded from our study. Patients’ demographic data, clinical and laboratory findings at the time of presentation, complications occurring during the course of treatment, immunosuppressants used along with steroids, and outcomes at the last follow-up were recorded. The mean duration of follow-up was 5.67 ± 3.07 years.ResultsOur results showed that there was male predominance (2.9:1), the mean age at first presentation was 4.53 ± 3.03 years, and persistent hematuria and systemic hypertension were found in 41.6% and 57.1%, respectively.The most common biopsy finding was MesPGN (37.3%). The most utilized immunosuppressant was cyclosporine (80.4%). Complete remission was fortunately the most prevalent outcome among our cases (52.2%).ConclusionsOur study concluded that biopsy findings and thepresence of hematuria in SRNS cases are the most crucial factors in determining the final outcome. MCNS finding in biopsy is significantly correlated with complete remission (p value = 0.043). Persistent hematuria whether gross or microscopic was significantly correlated with unremitting disease (p value = 0.017).

#2533 Real-world challenges associated with the use of systemic glucocorticoids in a US IgAN cohort

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and up to 50% of patients progress to kidney failure within 10-20 years. Until early 2022, management of IgAN was primarily focused on supportive care. As outlined in the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, patients at high risk of progressive chronic kidney disease despite maximal supportive care can be considered for a 6-month course of systemic glucocorticoids (SGC), although important risks of toxicity and contraindications must be considered. There is currently limited real-world evidence describing the impact of the use of SGC on treatment‑emergent toxicity and healthcare resource utilization (HCRU) in patients with IgAN. We report the incidence of adverse events (AEs) commonly associated with SGC, as well as HCRU rates and costs, in a real-world cohort of IgAN patients, comparing new initiators of SGC with patients who have never initiated SGC. Method This non-interventional, retrospective cohort study was conducted in the TriNetX Dataworks - United States of America Network, a database of de-identified, patient-level electronic medical records (EMR) of approximately 100 million patients. The cohort was selected from a total of 19, 687 patients with IgAN, identified using proxy ICD‑10 codes N02.8 (recurrent and persistent hematuria with other morphologic changes) or N04.1 (nephrotic syndrome) between January 1, 2011, and May 4, 2022. Eligible patients were required to have: an incident diagnosis of IgAN with the same diagnosis within 30-180 days; at least 12 months of EMR history available prior to and after initial IgAN diagnosis; not experienced kidney failure prior to or on the initial date of IgAN diagnosis; and not received SGC prior to the date of diagnosis. Data assessed included demographic and clinical characteristics, IgAN-directed medications, AEs, and HCRU. To promote balance between cohorts, new initiators of SGC (dexamethasone, prednisone, prednisolone, methylprednisolone) were matched with patients who did not receive SGC using a propensity score (PS) approach based on their characteristics at diagnosis. To avoid immortal-time bias, the index date was set as the time of SGC initiation in patients in the SGC cohort; for the non-SGC cohort, a pseudo-index date was assigned using the same lag from diagnosis to index date as their 1:1 PS-matched patient in the SGC cohort. Differences in the cumulative incidence of individual AEs were analyzed using the chi-square test or Fisher's exact test, and differences in HCRU rates and costs were analyzed using the Kruskal-Wallis test. Results After implementing the PS approach, the final analysis included 802 patients (401 PS-matched pairs), with a mean age of 41.2 years and 55% being male. Median duration of follow-up was 3.5 and 3.1 years for the SGC and non-SGC cohorts, respectively. Of AEs that occurred in at least ten of the 802 patients, patients who received SGC experienced a significantly increased incidence of all AEs except for fractures, new onset of diabetes, and reported onset of glaucoma (Table 1). Patients who received SGC had a 12-fold increased incidence of severe infections requiring hospitalization compared with the non-SGC cohort. Annualized mean HCRU rates and costs were significantly greater across all HCRU types for patients who received SGC vs those who did not receive SGC, including an 8-fold increase in inpatient visits, a 4-fold increase in emergency department admissions, and twice as many ambulatory visits (Fig. 1). Results were consistent when the cohort was restricted to patients with IgAN identified using only the ICD-10 code N02.8 (recurrent and persistent hematuria with other morphologic changes). Conclusion The findings of this real-world analysis demonstrate significant side effects and costs for IgAN patients treated with SGC compared with patients not treated with SGC, underscoring the recommendation in the 2021 KDIGO guidelines to carefully consider treatment-emergent toxicity before treating IgAN patients with SGC.

#123 Impact of atacicept on hematuria in IGA nephropathy: post-hoc analysis of the phase 2b ORIGIN study

Abstract Background and Aims Patients with IgA nephropathy (IgAN) and persistent hematuria during follow up have a greater decline in renal function than those with minimal or no hematuria, while hematuria resolution has been independently associated with less decline in renal function [1, 2]. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks for atacicept vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and robust reduction of galactose-deficient IgA1 vs placebo, with similar safety to placebo. This post-hoc analysis evaluates changes in hematuria during treatment with atacicept vs placebo over 36 weeks. Method The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24h urine protein &amp;gt;0.75 g/day or UPCR &amp;gt;0.75 g/g, and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Participants were randomized to atacicept 150, 75, or 25 mg vs placebo (2:2:1:2) self-administered by subcutaneous injection once weekly for up to 36 weeks. Microscopic hematuria was evaluated at weeks 2, 4, 12, 24, and 36 via urine dipstick at a centralized lab, and hematuria levels were graded negative/trace, 1+, 2+, or 3+. Hematuria improvement was defined as a decrease by ≥1 grade, and resolution was defined as a decrease to negative/trace. Results In the intent-to-treat population, 15 of 33 (45%) participants who received atacicept 150 mg and 19 of 34 (56%) who received placebo had hematuria (1+ or greater) at baseline. Of these, 87% (n = 13/15) on atacicept 150 mg had improved hematuria at 36 weeks vs 32% (n = 6/19) on placebo (p = 0.002), with 80% (n = 12/15) on atacicept 150 mg achieving resolution to negative/trace hematuria vs 5% (n = 1/19) on placebo (p &amp;lt; 0.0001) (Figure). The atacicept 150 mg group steadily improved to lower hematuria grades over 36 weeks, with improvement occurring as early as 4 weeks, while the placebo group had no improvement in hematuria over time. The majority of participants without hematuria at baseline maintained negative or trace levels at 36 weeks. Conclusion In a post-hoc analysis, atacicept treatment was associated with hematuria resolution at 36 weeks in a substantially greater percentage of participants as compared with placebo, with improvements seen as early as 4 weeks. These results add to the growing body of evidence supporting atacicept as a potential disease-modifying treatment for IgAN. Atacicept 150 mg is currently being evaluated in a global Phase 3 randomized placebo-controlled trial.

#1312 Warfarin-related nephropathy in two patients with mechanical valves

Abstract Background and Aims Warfarin-related nephropathy (WRN) is defined as acute kidney injury subsequent to excessive anticoagulation with warfarin. Patients with mechanical valves required long-term anticoagulant therapy, and warfarin remains the sole available option for anticoagulant therapy. Consequently, patients with mechanical valves constitute a special group among the entire anticoagulant population. Method The present study recorded two patients receiving warfarin therapy for mechanical valve presented to the hospital with gross hematuria and progressive creatinine levels. Results The first patient was a 56-year-old female, who had previously undergone mechanical aortic valve replacement surgery nine months ago and was prescribed warfarin, was admitted to the hospital due to the occurrence of gross hematuria six days before hospitalization. Additionally, her creatinine levels exhibited a rapid increase from 120.5umol/L to 207.5 μmol/L within three days. Laboratory analysis revealed a creatinine level of 167.8 μmol/L, albumin level of 39.6 g/L, and an INR value of 2.08. The urinary test results indicated the presence of urinary protein (+) and urinary occult blood (3+). The quantification of urinary protein over a 24-hour period was measured at 0.69 g. The immunoglobulin, complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. The second patient was a 63-year-old male, who has been diagnosed with hypertension for the twenty years, underwent Bentall+Sun's surgery for type A aortic dissection five years ago. Following the surgery, the patient was prescribed warfarin. The patient was admitted to the hospital due to persistent gross hematuria for a duration of twenty days and an increase in creatinine levels. Upon admission, laboratory analysis revealed a creatinine level of 169.9μmol/L (which was within the normal range one year ago), and an INR of 2.69. The urinary test indicated the presence of urinary protein (2+) and urinary occult blood (3+). Urinary protein quantification was 3.06 g/24 hours. The serum IgA level was measured at 4.55 g/L (normal range: 1.0-4.2 g/L). The complements, ANA, ANCA, anti-GBM antibody, serum protein electrophoresis, serum light chains and PLAR2 were within normal range. Pathology of two patients all showed red blood casts and tubular injury consistent with ARN and underlying IgA nephropathy (Fig. 1). The two patients was administered a daily dosage of 20 mg of prednisolone and an oral dosage of 50 mg of cyclophosphamide every other day. During a subsequent follow-up after a two-month period, the first patient's creatinine had decreased to 109.2μmol/L, and the urine protein quantification was recorded as 119.7 mg/24 hours. The second patient's creatinine had decreased to 159.2 μmol/L, and the quantification of urine protein was recorded at 310 mg/24 hours. Conclusion Clinicians should maintain a state of increased alertness with regards to the potential occurrence of WRN who exhibit hematuria and elevated creatinine levels while on warfarin therapy, even if their INR remains within the normal range. Considering most patents of WRN have an underlying glomerular disease (mostly IgA nephropathy), the use of steroids and immunosuppressive drugs may appear to be an attractive option, particularly in patients who are unable to replace warfarin with direct oral anticoagulants (NOACs).

#817 Genetic analysis in a group of patients with persistent isolated microscopic hematuria

Abstract Background and Aims Autosomal dominant Alport syndrome (ADAS) is a genetic disease caused by pathogenic variants in COL4A3 and COL4A4 genes. ADAS is the main cause of isolated persistent microscopic hematuria (PMH). However, other diseases like IgA nephropathy (IgAN) can present with PMH. Establishing a precise genetic diagnosis in this type of patients would avoid invasive studies like kidney biopsies. In this study we performed a comprehensive genetic test in a cohort of patients with isolated PMH to evaluate the frequency of ADAS or other genetic abnormalities and compare the clinical characteristics of patients with or without ADAS Method Fifty-two patients with PMH were included in the study. PMH was defined by the presence of 3 or more dysmorphic red blood cells per field in at least 5 consecutive urine sediments and a time-averaged proteinuria &amp;lt;1 gr/day. Average proteinuria was determined for every 6 months of follow-up and time-averaged (TA) proteinuria represented an average of the mean proteinuria measurements in each 6-month period. A comprehensive genetic study using whole exome next-generation sequencing was performed. One hundred and one genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney diseases were analyzed. Patients with known secondary causes of hematuria were excluded. The baseline clinical characteristics of patients with and without ADAS were compared. Patients with pathogenic variants in COL4A5 gene were excluded of this analysis. Results Thirty-one (60%) patients were diagnosed with ADAS (16 patients with pathogenic variants in COL4A3, 15 in COL4A4), 3 (6%) patients (2 women, 1 man) presented pathogenic variant in COL4A5 gene, and the genetic study was negative in the remaining 18 patients (variants of unknown significance in COL4A3 or COL4A4 were found in 3 of the latter). No other genetic abnormalities were detected in the panel of 101 genes. Table 1 shows the baseline clinical characteristics of patients with and without ADAS. Patients with ADAS presented a higher TA proteinuria [0.23 (0.11-0.6) vs 0.08 (0.05-0.16), p = 0.01], and a more frequent familial history of isolated microscopic hematuria (76% vs 40%, p = 0.01) chronic kidney disease (CKD) (44% vs 0%, p = 0.01) or end stage kidney disease (32% vs 0%, p = 0.02). In the multivariate analysis, only a family history of microscopic hematuria was associated with ADAS: OR 5.62 (1.25-25.49, p = 0.02). Conclusion ADAS is the most common cause of PMH. A genetic study should be the first diagnostic step in order to obtain a precise cause of the disease and avoid invasive procedures. A family history of microscopic hematuria and of CKD increases the likelihood of ADAS prior to the performance of genetic test.

#1063 Presentation, treatment, and outcome of IgA nephropathy in children: comprehensive characterization of a Croatian single centre cohort

Abstract Background and Aims IgA nephropathy (IgAN) is a complex disease diagnosed only upon evaluation of a kidney biopsy. Since the threshold to perform this invasive procedure is higher and symptoms usually more indolent in children, the true prevalence might be underestimated, with fewer studies examining the presentation, treatment, and outcome of IgAN in paediatric population. Moreover, there is a substantial heterogeneity of clinical presentation and pathological features between geographical locations, with fewer data available for region of central and southern Europe. We therefore aim to provide a conscientious description of a paediatric IgAN cohort followed for an extended period of time in a centre caring for most of the Croatian paediatric patients. Method Single centre retrospective study of children newly diagnosed as IgAN since 2011 and followed for &amp;gt;2 years in a tertiary referral centre for paediatric nephrology of the Republic of Croatia. Results Total of 15 paediatric (&amp;lt;18 years) patients were included, of which 11 (73%) were male, 14 Caucasians and 1 of Roma origin. All the patients had proteinuria (&amp;gt;150 mg/day) and hematuria (&amp;gt;5 RBC/mm3 in uncentrifuged urine) at the time of the biopsy, with the mean age of 12.2 ± 3.6 years. The median eGFR was 87 (69 – 111) mL/min/1.73m2 and the median value of proteinuria 260 (150 – 370) mg/day. More specifically, 2 patients had mild proteinuria (&amp;lt;20 mg/kg/day), 12 had moderate (20 – 50 mg/kg/day) and 1 had nephrotic range (&amp;gt;50 mg/kg/day). The results of biopsy in terms of MEST-C score showed M1 in 4, E1 in none, S1 in 3, T1 in 4, T2 in 0, C1 in 2 and C2 in none of the patients. The IF was positive for IgA and C3 in all patients, and in 1 for C1q. There was no significant correlation between C3 intensity values (0-4+) and 24 h proteinuria (r = 0.49, p = 0.06) or eGFR (r = −0.22, p = 0.43). Hypertension (≥95 percentile for age) was present in 2 (13%) patients. The median risk of a 30% decline in eGFR or progression to end-stage renal disease 5 years after renal biopsy calculated by International IgAN prediction tool for use in paediatric patents was 8.03% (4.58 – 11.27). Initial presenting episode was treated with ACEi in 7 (47%) and with glucocorticoids in 4 (27%) patients. There was no significant difference in proteinuria (p = 0.19) or risk of decline in eGFR or progression to ESRD (p = 0.16) among treated and untreated patients. In all of the treated patients proteinuria reached a target of &amp;lt;20 mg/kg during the median time of 11 (6 – 21) months. The median follow up was 6.5 (2.8 – 11.1) years. During the follow up 5 patients experienced first relapse of proteinuria, 3 had second and none had third relapse. None of the patients had adverse event related to medications. None were treated with renal replacement therapy or other immunomodulatory drugs. Tonsillectomy was performed in two patients with a substantial improvement of haematuria episodes reported by caregivers. Omega-3 polyunsaturated fatty acid was used in 1 patient. While none of the patients developed CKD during the follow up, none have reached complete renal remission defined as eGFR &amp;gt;90 ml/min/1.73m2, proteinuria &amp;lt;150 mg/day and RBC &amp;lt; 5/mm3 in urinalysis. Conclusion All the patients in our cohort had indolent disease with proteinuria, along with low risk of decline in eGFR or progression to ESRD after biopsy. Almost half of them were treated with ACEi, and a quarter with glucocorticoids, all with beneficial response. Nevertheless, none of the patients in the cohort achieved full renal remission due to the persistent hematuria. While there are few well performed studies on the treatment of IgAN in adult patients, to date, there are no high-quality randomised studies on immunosuppressing and other drugs, as well as nutritional and other interventions in children with IgAN, prompting a case-to-case decision regarding the use of various therapeutic modalities. Therefore, well characterized cohorts from around the globe might provide further reassurance for physicians taking care of children with this intricating disease, support when deciding to commence the intervention and inform while selecting the most appropriate form.

Surgical treatment of Nutcracker Syndrome

The objective of this paper is to report early and mid-term outcomes of the surgical treatment Nutcracker Syndrome (NCS) in a single-center prospective study. Between January 2019 and September 2023, five patients with symptomatic NCS were treated at our center using left renal vein caudal transposition on the inferior vena cava, conducted through a midline incision of approximately 12 cm and a transperitoneal technique. Patient characteristics, presentation, length of hospital stay, and complications were analyzed. All diagnoses were established after clinical evaluation, ultrasound scanning, and radiological investigations, which confirmed left renal vein compression between the aorta and the Superior Mesenteric Artery (SMA). The average operating time was 159 minutes, with an average blood loss of 205 mL. There was no need for blood transfusions. Intensive care stay was not required and there were no early complications. The mean length of stay was 3.5 days. At a mean follow-up of 18.8 months, one patient reported persistent hematuria, and therefore underwent a secondary procedure, which incorporated patch venoplasty using the great saphenous vein. In our experience, left renal vein transposition appears to be a safe and effective procedure for the surgical management of severe NCS.

Spontaneous Large Renal Pelvis Haematoma in Ureteropelvic Junction Obstruction: A Rare Case Report

Spontaneous renal haemorrhage is a rare occurrence with potentially serious consequences. This presented case was an even rarer form of ureteropelvic obstruction (UPJO), which was spontaneous bleeding into the renal pelvis in a patient who was not previously investigated for UPJO. We presented a 17-year-old gentleman who presented with lower abdominal pain for one week and painless haematuria for two days. Initial computed tomography angiography (CTA) renal revealed haematoma with a grossly dilated pelvicalyceal system. The patient was initially treated conservatively. However, in the ward, he suddenly developed severe left-sided back pain, decreased haemoglobin level and persistent gross haematuria. Repeated CTA renal revealed worsening left renal haematoma with a grossly dilated pelvicalyceal system, and he was panned for nephrectomy. A review of the literature followed with a discussion of the case were done in this study.

Nephrology referral slows the progression of chronic kidney disease, especially among patients with anaemia, diabetes mellitus, or hypoalbuminemia: A single-centre, retrospective cohort study.

The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion-based and which patients with CKD benefit more from nephrology referral has not been elucidated. In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m2). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated. The eGFR slope significantly improved from -2.05 (-2.39 to -1.72) to -0.96 (-1.36 to -0.56) mL/min/1.73 m2/year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p-values for three-way interaction <.001 after adjustment for covariates). Further adjustments for time-dependent haemoglobin levels, the use of erythropoiesis-stimulating agents, iron supplementation, anti-hypertensives and anti-diabetic medications did not change the significance of the interactions. Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered.

One-Year Outcomes of Transurethral Treatment of Bladder Neck Stenosis Following Transurethral Resection of the Prostate. Results from a Large, Multicenter Series.

To assess management and outcomes of bladder neck stenosis (BNS) post-transurethral resection of the prostate (TURP) in 12 centers. A retrospective analysis of patients who underwent transurethral BN incision for stenosis following TURP from January 2015 and January 2023 was performed. Inclusion criteria included endoscopic diagnosis of BNS associated with obstruction and/or lower urinary tract symptoms. Data are presented as median and interquartile range. Two distinct univariable logistic regression analyses were performed to identify factors associated with overall urinary incontinence and recurrent stenosis. Three hundred and seventy-two men were included. 95.2% of patients developed BNS following bipolar TURP. 21.0% of patients were on an indwelling catheter before BNS incision. Bipolar electrocautery was the most commonly employed energy for incision (66.5%). Collings knife was the most commonly employed (61.2%) instrument for incision, followed by end-firing holmium lasering (35.3%). Median operation time was 30 (25-45) minutes. The overall complication rate was 12.4%, with 19 (5.1%) patients suffering from acute urinary retention, 6 (1.6%) patients requiring prolonged irrigation due to persistent hematuria, and a surgical hemostasis was necessary in 8 cases (2.2%). Overall postoperative incontinence rate was 17.2%, with urge incontinence accounting for the most common type (45.3%). Incontinence lasted more than 3 months in 9/46 (14.3%) patients. Recurrent BNS occurred in 29 (7.8%) patients and was managed by re-endoscopic incision in 21 (5.6%) patients and dilatation only in 6 (1.6%) patients. Two (0.5%) patients underwent urethroplasty for recalcitrant stenosis. Logistic regression analysis showed that Collings knife was associated with higher odds of having postoperative incontinence (OR 3.93 95% CI 1.45-11.13, p=0.008) and BN recurrence (OR 3.589 95% CI 1.157-15.7, p=0.047). Transurethral BN incision provides satisfactory short-term results with an acceptable rate of complications.

The Impact of SARS-CoV-2 on Patients With Lower Urinary Tract Symptoms (LUTS).

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the management of patients with lower urinary tract symptoms (LUTS) underwent dynamic adjustments in response to an evolving understanding of the virus's impact on different patient populations. Healthcare practitioners reevaluated therapeutic approaches for conditions like benign prostatic hyperplasia (BPH), considering the potential implications of this condition on the severity and progression of coronavirus disease 2019 (COVID-19). This study aims to investigate potential correlations between SARS-CoV-2 infection severity, exacerbation of LUTS, and BPH progression. This retrospective study includes patients hospitalized in our Urology Department between January 2021 and January 2023, presenting with both SARS-CoV-2 and BPH. Their ages ranged from 57 to 88 years, with a mean age of 65.4 years. The diagnosis of BPH relied on a diagnostic triad consisting of digital rectal examination, biological markers (including prostate-specific antigen (PSA) and free PSA, and ultrasound examination, with both conditions confirmed based on test results. Transurethral resection of the prostate (TURP) procedures utilized monopolar Karl Storz resection equipment, using sorbitol and bipolar Olympus devices for transurethral resection of the prostate in saline (TURPis). Haemostasia was performed using roller balls. Anticoagulation followed a prescribed scheme by cardiologists and infectious disease specialists. Statistical analysis was conducted using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Among the 138 hospitalized patients affected by both BPH and COVID-19, 18 required emergency endoscopic procedures (specifically TURP or TURPis) to achieve hemostasis (Figures 1, 2). These individuals presented persistent hematuria despite conservative treatments. The mean duration of surgery was 57.9 minutes. Patients who underwent surgery had a longer average hospital stay compared to those who did not, with durations of 10.5 days versus 7.5 days, respectively. Additionally, urethrovesical catheter insertion was necessary in 29 cases due to acute urinary retention or worsening voiding symptoms during hospitalization. These patients are scheduled for further urological evaluation following the resolution of the COVID-19 episode. In a cohort of 53 patients for whom data were accessible, comparisons were made between the pre-COVID status and the levels of the International Prostate Symptom Score (IPSS), post-voiding residue (PVR), and quality of life (QoL). The findings revealed a mean pre-COVID IPSS value of 11.6 and a COVID-related value of 14.2, with a statistically significant difference noted (p < 0.05). The mean pre-COVID PVR was 42.3 cm2, whereas during the COVID-19 period, it measured 62.5 cm2, also exhibiting a significant difference (p < 0.05). Additionally, the QoL showed a mean pre-COVID-19 score of 2.4 and a COVID-19-associated score of 2.9, again demonstrating statistical significance (p < 0.05). The onset of the SARS-CoV-2 pandemic posed novel challenges in the medical realm, impacting the approach to BPH management. A common practice was delaying treatment for chronic BPH until viral infection remission to reduce associated risks. Additionally, our study revealed a worse evolution in LUTS among individuals with severe COVID-19 symptoms.

Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome.

Autosomal dominant Alport Syndrome (ADAS), also known as thin basement membrane disease (TBMD), is caused by pathogenic variants in the COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies have been performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with chronic kidney disease (CKD). This was a retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4±9.6years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an estimated glomerular filtration rate (eGFR) <45mL/min/1.73 m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7±5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR <45mL/min/1.73 m2 (63% vs 7%, P=.006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06mL/min/1.73 m2/year (P=.009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (P=.002) and MKD (P=.02). MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.

Late Arteriovenous Fistula after transurethral resection of the prostate: case report

This study describes a case of symptomatic arteriovenous fistula after Transurethral Resection of the Prostate diagnosed by urethrocystoscopy and confirmed by imaging tests. The patient presented lower urinary tract symptoms associated with hematuria twenty years after being submitted to a TURP. Arterial and venous tomography angiography of the pelvis visualized a hypervascularized lesion involving the membranous urethra and aneurysm of the right external iliac artery. The patient underwent embolization of bilateral prostatic arteries with good post-embolization recovery and complete remission of urinary symptoms. Arteriovenous fistula after transurethral resection of the prostate is a rare pathology that must be considered in the differential diagnosis of persistent hematuria and infravesical obstruction without significant prostatic enlargement. In cases like this, embolization has become a new therapeutic option with excellent obliteration rates and minimal morbidity.

Immune Thrombocytopenic Purpura: An uncommon manifestation of Hepatitis A with acute liver failure

&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Hepatitis A Virus (HAV) infection is a benign, self-limited gastrointestinal infection of children. Autoimmune hematological manifestation is very rare in children. Here, we report an 11-year-old male child having HAV infection with acute liver failure, complicated with persistent thrombocytopenia and haematuria during the course of illness and eventually diagnosed as a case of HAV infection associated with immune thrombocytopenic purpura. The child was treated successfully with a short course of steroid therapy.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;