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Гематурия — это наличие пяти или более эритроцитов в трех последовательных анализах мочи, полученных с интервалом в одну неделю. На уровне первичной медицинской помощи врач должен уметь распо­знать и подтвердить наличие гематурии, предположить ее возможные причины, провести отбор пациентов, которые потенциально могут иметь тяжелое заболевание мочевой системы. Алгоритм оказания первичной медицинской помощи при гематурии у детей зависит от ее клинического варианта: макрогематурия, симптоматическая микрогематурия, асимптоматическая микрогематурия с протеинурией, асимптоматическая изолированная микрогематурия. Детям с макрогематурией показано следующее обследование: общий анализ мочи, общий анализ крови, креатинин сыворотки, соотношение кальций/креатинин в разовой моче, УЗИ почек и мочевого пузыря. Если в результате уточнения жалоб, анамнеза, объективного и дополнительного обследования причина макрогематурии не установлена, ребенка следует направить к детскому нефрологу. Оценка детей с симптоматической микрогематурией направлена на выявление общих (лихорадка, недомогание, боль в животе и др.), неспецифических (сыпь, артрит, желтуха, респираторные, желудочно-кишечные симптомы и др.) и специфических для мочевой системы (дизурия, поллакиурия, недержание мочи, энурез, отеки, артериальная гипертензия) симптомов. Наличие гематурии в сочетании с протеинурией у детей чаще всего предполагает гломерулярное происхождение гематурии. Бессимптомные пациенты, у которых сохраняются гематурия и протеинурия в течение 2–3 недель, должны быть направлены к детскому нефрологу для дальнейшего обследования. Бессимптомная изолированная микрогематурия является наиболее распространенным вариантом гематурии у детей, обычно кратковременным и, как правило, не связанным с тяжелым почечным заболеванием. Наиболее распространенными причинами персистирующей более шести месяцев асимптоматической микрогематурии являются IgA-нефропатия, болезнь тонких базальных мембран, менее частыми — наследственный нефрит (синдром Альпорта), гиперкальциурия, инфекция мочевых путей. На этапе дообследования и дальнейшего наблюдения детей с асимптоматической изолированной микрогематурией оптимальным лекарственным средством является фитониринговый препарат Канефрон® Н.

The extracellular matrix (ECM) is a complex network of collagens, elastin, and interconnecting glycoproteins and proteoglycans that surround cells and provide structural support. The ECM is a dynamic structure, undergoing constant remodeling, and providing services beyond a simple barrier or scaffold (1). Recent studies have demonstrated that the ECM and the broad complement of interacting proteins ( e.g. the matrisome) play significant roles in inflammation and cell-to-cell interactions (2). Low-grade inflammation, a common feature of many kidney diseases, often contributes to aberrant ECM deposition and fibrosis. Significantly, renal fibrosis is a hallmark of renal dysfunction progression and CKD, leading to end-organ failure. Many of the proteins making up the renal ECM are spatially resolved into the glomerular (glomerular basement membrane, the mesangial matrix, and Bowman’s capsule) and tubulointerstitial (tubular basement membranes, tubular capillaries, and interstitial space) compartments. The most abundant proteins in the ECM are collagens, accounting for almost one third of ECM proteins (3). Type IV collagen is the most well described ECM protein in terms of kidney disease. Type IV collagen has six alpha chains that form three different trimer combinations, and the α3.α4.α5 heterotrimer is the most predominant in the glomerular basement membrane (3). Mutations in COL4A3 , COL4A4 , or COL4A5 genes are associated with Alport Syndrome, thin basement membrane disease, and familial FSGS (4,5). Proteomic analysis has identified collagens I, III, VI, VII, XII, XV, and XVIII within the glomerular ECM (6,7). Collagens I, II, III, V, VI, VII, and XV are normally expressed in the tubulointerstitium and increased expression have been associated with fibrosis (3). A recent proteomic analysis of kidneys across different age groups demonstrated consistent increases in collagen VI with aging kidneys (8). Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE), …

BACKGROUND: Autosomal recessive Alport syndrome (ARAS) is an inherited renal disorder caused by homozygous and compound heterozygous mutations in COL4A3 or COL4A4, but the prognostic predictors for this disorder are not yet fully understood. Recently, the magnitude of the clinical spectrum of the COL4A3 and COL4A4 heterozygous state has attracted attention. This spectrum includes asymptomatic carriers of ARAS, benign familial hematuria, thin basement membrane disease, and autosomal dominant Alport syndrome. METHODS: We retrospectively analyzed 49 patients with ARAS from 41 families with a median age of 19 years to examine the clinical features and prognostic factors of ARAS, including the associated genotypes. RESULTS: The median age of patients with ARAS at ESKD onset was 27 years. There was no significant association between the presence or absence of hearing loss or truncating mutations and renal prognosis. However, there was a statistically significant correlation between renal prognosis and heterozygous variants that cause urinary abnormalities. Where the urinary abnormality–causing variant was absent or present in only one allele, the median age of ESKD onset was 45 years, whereas the same variant present on both alleles was associated with an age of onset of 15 years (P

BackgroundPatients heterozygous for COL4A3 or COL4A4 mutations show a wide spectrum of disease, extending from familial isolated microscopic haematuria, as a result of thin basement membranes (TBMs), to autosomal dominant Alport syndrome (ADAS) and end-stage renal disease (ESRD). Many patients are mentioned in the literature under the descriptive diagnosis of TBM nephropathy (TBMN), in which case it actually describes a histological finding that represents the carriers of autosomal recessive Alport syndrome (ARAS), a severe glomerulopathy, as most patients reach ESRD at a mean age of 25 years.MethodsWe performed a systematic literature review for patients with heterozygous COL4A3/A4 mutations with the aim of recording the spectrum and frequency of pathological features. We searched three databases (PubMed, Embase and Scopus) using the keywords ‘Autosomal Dominant Alport Syndrome’ OR ‘Thin Basement Membrane Disease’ OR ‘Thin Basement Membrane Nephropathy’. We identified 48 publications reporting on 777 patients from 258 families.ResultsIn total, 29% of the patients developed chronic kidney disease (CKD) and 15.1% reached ESRD at a mean age of 52.8 years. Extrarenal features and typical Alport syndrome (AS) findings had a low prevalence in patients as follows: hearing loss, 16%; ocular lesions, 3%; basement membrane thickening, 18.4%; and podocyte foot process effacement, 6.9%. Data for 76 patients from 54 families emphasize extensive inter- and intrafamilial heterogeneity, with age at onset of ESRD ranging between 21 and 84 years (mean 52.8).ConclusionsThe analysis enabled a comparison of the clinical course of patients with typical ARAS or X-linked AS with those with heterozygous COL4A mutations diagnosed with TBMN or ADAS. Despite the consequence of a potential ascertainment bias, an important outcome is that TBM poses a global high risk of developing severe CKD, over a long follow-up, with a variable spectrum of other findings. The results are useful to practicing nephrologists for better evaluation of patients.

Background Oculocerebrorenal syndrome of Lowe is a rare X-linked disorder characterized by congenital cataracts, mental retardation, and proximal tubulopathy. This condition is caused by a mutation of OCRL gene (located at chromosome Xq26.1), which encodes an inositol polyphosphate 5-phosphatase. Case presentation We identified two novel OCRL mutations in two unrelated Chinese boys, each with a severe phenotype of Lowe syndrome. A novel de novo deletion (hemizygous c.659_662delAGGG, p.E220Vfs*29) was present in patient 1 and a novel splicing mutation (hemizygous c.2257-2A > T) that was maternally inherited was present in patient 2. A renal biopsy in patient 2 indicated mild mesangial proliferative glomerulonephritis, mild focal mononuclear cells infiltration, and interstitial focal fibrosis. Moreover, renal expression of OCRL-1 protein in patient 2 was significantly reduced compared to a control patient with thin basement membrane disease. Conclusions This study reports two novel OCRL variants associated with severe ocular and neurologic deficiency, despite only mild renal dysfunction. Based on our two patients and a literature review, the genotype–phenotype correlation of OCRL mutations with this severe phenotype of Lowe syndrome suggest a possible clustering of missense, deletion, and nonsense mutations in the 5-phosphatase domain and Rho-GAP domain in the Chinese population.

Introduction Routine C4d staining in renal transplantation has stimulated its use in kidney biopsies with glomerulonephritis (GN). Methodical description on staining patterns in the native kidney is not available. Methods We retrospectively evaluated C4d staining in formalin-fixed paraffin-embedded sections from 519 native kidney biopsies (bx) with and without glomerular disease. Results Strong C4d staining was consistently present in immune-complex GN, including lupus nephritis (LN) (n = 68), membranous GN (n = 24), membranoproliferative glomerulonephritis (MPGN) pattern (n = 22), fibrillary GN (n = 3), and proliferative GN with monoclonal IgG (n = 3). C4d stained all cases of postinfectious GN (n = 7) amyloidosis (n = 20) and C1q GN (n = 3). In contrast, IgA nephropathy (IgAN) (n = 34), was negative in 62% of bx, with the rest staining variably. The E1 Oxford classification score correlated with capillary wall C4d staining (P = 0.05). C4d marked the glomerular and arteriolar lesions in thrombotic microangiopathy (TMA; n = 16), the glomerular sclerotic segments in focal segmental glomerulosclerosis (FSGS; n = 77), and marked areas of necrosis in crescentic GN (n = 21). In diabetic glomerulopathy (n = 70), C4d marked advanced insudative lesions but was negative otherwise. C4d weakly stained the mesangium, or was negative in normal biopsies (n = 13), minimal change disease (MCD; n = 21), thin basement membrane disease (n = 20), Alport (n = 3), IgM nephropathy (n = 2), C3 glomerulopathy (n = 5), acute interstitial nephritis (n = 12), acute tubular necrosis (n = 22), ischemic glomerulopathy/nephrosclerosis (n = 23), and other miscellaneous processes (n = 14). Staining in tubular basement membranes and peritubular capillaries was most common in lupus. Conclusion Based on reliable staining in lupus and membranous GN, C4d staining is potentially useful as a screening and diagnostic tool, if only paraffin-embedded tissue is available. Knowledge of C4d staining patterns in normal and pathological tissues enhances its diagnostic value., Graphical abstract

A 21-year-old woman was referred to our hospital because of proteinuria and hematuria. She had occasional flank pain. A renal biopsy was performed and revealed a thin basement membrane. Therefore, she was diagnosed with thin basement membrane disease. However, the frequency of her flank pain increased. Since her left kidney was slightly larger than the right, nutcracker syndrome (NCS) was suspected. Renal vein ultrasonography and venography were performed, and NCS was confirmed. Her hematuria was multifactorial, and NCS can go unnoticed if there is a comorbidity that also causes hematuria.

Artificial intelligence (AI) is a new frontier and often enigmatic for medical professionals. Cloud computing could open up the field of computer vision to a wider medical audience and deep learning on the cloud allows one to design, develop, train and deploy applications with ease. In the field of histopathology, the implementation of various applications in AI has been successful for whole slide images rich in biological diversity. However, the analysis of other tissue medias, including electron microscopy, is yet to be explored. The present study aims to evaluate deep learning for the classification of medical kidney disease on electron microscopy images: amyloidosis, diabetic glomerulosclerosis, membranous nephropathy, membranoproliferative glomerulonephritis (MPGN), and thin basement membrane disease (TBMD). We found good overall classification with the MedKidneyEM-v1 Classifier and when looking at normal and diseased kidneys, the average area under the curve for precision and recall was 0.841. The average area under the curve for precision and recall on the disease only cohort was 0.909. Digital pathology will shape a new era for medical kidney disease and the present study demonstrates the feasibility of deep learning for electron microscopy. Future approaches could be used by renal pathologists to improve diagnostic concordance, determine therapeutic strategies, and optimize patient outcomes in a true clinical environment.

Altres ajuts: The author's research is funded by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (FEDER) funds, RETIC REDINREN RD16/0009 FIS FEDER FUNDS. In this issue, Matthews et al. provide a comprehensive review of published cohorts with heterozygous pathogenic variants in COL4A3 or COL4A4, documenting the wide spectrum of the disease. Due to the extreme phenotypes that patients with heterozygous pathogenic variants in COL4A3 or COL4A4 may show, the disease has been referred to in a variety of ways, including 'autosomal dominant Alport syndrome', 'thin basement membrane disease', 'thin basement membrane nephropathy', 'familial benign hematuria' and 'carriers of autosomal dominant Alport syndrome'. This confusion over terminology has prevented nephrologists from being sufficiently aware of the relevance of the entity. Nowadays, however, next-generation sequencing facilitates the diagnosis and it is becoming a relatively frequent finding in haematuric-proteinuric nephropathies of unknown origin, even in non-familial cases. There is a need to raise awareness among nephrologists about the disease in order to improve diagnosis and provide better management for these patients.

Rationale & Objective: Alport syndrome is a common genetic kidney disease accounting for approximately 2% of patients receiving kidney replacement therapy (KRT). It is caused by pathogenic variants in the gene COL4A3, COL4A4, or COL4A5. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome (ADAS). Study Design: Retrospective cohort study. Setting & Participants: 82 families (252 patients) with ADAS were studied. Clinical, genetic, laboratory, and pathology data were collected. Observations: A pathogenic DNA variant in COL4A3 was identified in 107 patients (35 families), whereas 133 harbored a pathogenic variant in COL4A4 (43 families). Digenic/complex inheritance was observed in 12 patients. Overall, the median kidney survival was 67 (95% CI, 58-73) years, without significant differences across sex (P = 0.8), causative genes (P = 0.6), or type of variant (P = 0.9). Microhematuria was the most common kidney manifestation (92.1%), and extrarenal features were rare. Findings on kidney biopsies ranged from normal to focal segmental glomerulosclerosis. The slope of estimated glomerular filtration rate change was -1.46 (-1.66 to -1.26) mL/min/1.73 m(2) per year for the overall group, with no significant differences between ADAS genes (P = 0.2). Limitations: The relatively small size of this series from a single country, potentially limiting generalizability. Conclusions: Patients with ADAS have a wide spectrum of clinical presentations, ranging from asymptomatic to kidney failure, a pattern not clearly related to the causative gene or type of variant. The diversity of ADAS phenotypes contributes to its underdiagnosis in clinical practice.

Akiko Inoue-Torii,1 Shinji Kitamura,1 Jun Wada,1 Kenji Tsuji,2 Hirofumi Makino1 1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Center for Systems Biology, Program in Membrane Biology, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, MA, USA Abstract: Semaphorin3A is a secreted protein known to be involved in organogenesis, immune responses and cancer. In the kidney, semaphorin3A is expressed in the glomerular podocytes, distal tubules and collecting tubules, and believed to play a role in the regulation of the kidney development and function. We examined the serum and urinary semaphorin3A levels in 72 patients with renal disease and 5 healthy volunteers. The patients had been diagnosed with thin basement membrane disease (n=4), minimal change nephrotic syndrome (MCNS; n=22), IgA nephritis (n=21), membranous nephropathy (n=16) and focal segmental glomerular sclerosis (n=9). The level of urinary semaphorin3A in MCNS patients tended to be relatively high among all disease groups. We also investigated the urinary semaphorin3A level in 7 patients with MCNS from disease onset to remission during the drug therapy. MCNS patients in pre-remission states had higher urinary semaphorin3A levels than those in post-remission states receiving immunosuppressive therapies. These results suggested that the urinary semaphorin3A level correlates with the MCNS activity. Semaphorin3A has the potential as a biomarker for MCNS to clarify the reactivity for therapy and may be useful in examining other glomerular diseases with proteinuria as well. Keywords: semaphorin3A, biomarker, minimal change nephrotic syndrome

Hematuria is a common problem in pediatric practice and necessitates exhausting studies to detect etiology and establish proper management and counselling. We reviewed the clinical and pathological findings in 95 children presented between 2013 and 2019 with gross or microscopic hematuria with or without proteinuria in whom non-glomerular causes were excluded. In addition, a reference range for normal glomerular basement membrane thickness (GBMT) is introduced based on the assessment of biopsies of 20 steroid-resistant nephrotic syndrome cases aged 3–15 years, and with minimal change pathology. Fifty-seven males and 38 females with a mean age of 7.72 ± 3.27 years were included. Recurrent gross hematuria was the most frequent presentation (42%) while accidentally discovered hematuria was reported in 34.7% of patients. Alport syndrome (AS) was the most frequent diagnosis (66.3%) followed by thin basement membrane disease (TBMD) (29.5%) and Immunoglobulin A nephropathy (IgAN) (4%). A reference for normal GBMT was 360.3 ± 87.5 nm which is comparable to published references. Males with AS had a higher incidence of progression to renal failure and requirement for dialysis (p = 0.006 and 0.03, respectively) compared to females. Persistent proteinuria and lower glomerular filtration rate at diagnosis were associated with poor outcomes (p

Background: Electron microscopy (EM) provides another diagnostic assessment of glomerular lesions in addition to light and fluorescent microscopy. Objectives: We evaluated the contribution of diagnostic EM in childhood glomerular diseases. Patients and methods: Forty-eight renal biopsies which were assessed by EM between 2000 and 2014 were evaluated. Results: There were 21 (44%) females and 27 (56%) males, ages ranged between 6 and 204 months. EM findings were compatible with light and immunofluorescence microscopy in 65%, made additional contributions to diagnosis in 31% (especially in focal segmental glomerulosclerosis, Alport disease, membranoproliferative glomerulonephritis, dense deposit disease, thin basement membrane disease, and nephronophthisis), and was non-contributory in 4%. Conclusion: Electron microscopic evaluation supports other histopathological diagnoses in most cases, contributes additional diagnostic information in pediatric glomerular disease, especially in FSGS, thin glomerular basement membrane nephropathy, Alport disease, MPGN, and dense deposit disease, and its utilization should clinically justify the increase in cost and testing time.

We report a case of a 48-year-old male who presented with hematuria of at least 10 years, and has a daughter with hematuria as well. The patient has a history of degenerative hearing loss, decreased vision and cataract formation, but no diabetes, hypertension or proteinuria. A full serology and urology workup was negative for any abnormality. A kidney biopsy for the patient revealed a diagnosis of Alport syndrome but was unable to rule out thin basement membrane disease. The biopsy was inconclusive in making the diagnosis but the patient's clinical presentation led to the diagnosis of Alport syndrome. The patient's 10-year-old daughter also has hematuria with no clear etiology but now can subsequently be anticipatorily managed for Alport syndrome progression. Due to the rarity of the disease, diagnosis is often missed or delayed by primary care providers especially when no associated proteinuria has yet developed. This can lead to confusion and misdiagnosis with thin basement membrane disease, a generally benign hematuria without kidney failure progression. Additionally, biopsy can be inconclusive in these patients, relying on the physician's history and physical examination findings to diagnose. It is important to appropriately diagnose Alport syndrome not only to manage the patient's rate of kidney failure progression but also allow for a higher degree of suspicion, screening and intervention in the patient's family members. Both the inconclusive nature of kidney biopsies and the usefulness of diagnosis for family member screening are often overlooked in medical literature but are explored in this case.

Patients with autosomal or X-linked Alport syndrome (AS) with heterozygous mutations in type IV collagen genes have a 1-20 % risk of progressing to end-stage renal disease during their lifetime. We evaluated the long-term renal outcome of patients at risk of progressive disease (chronic kidney disease stages 1-4) with/without nephroprotective therapy.This was a prospective, non-interventional, observational study which included data from a 4-year follow-up of AS patients with heterozygous mutations whose datasets had been included in an analysis of the 2010 database of the European Alport Registry. Using Kaplan-Meier estimates and logrank tests, we prospectively analyzed the updated datasets of 52 of these patients and 13 new datasets (patients added to the Registry after 2011). The effects of therapy, extrarenal symptoms and inheritance pattern on renal outcome were analyzed.The mean prospective follow-up was 46 ± 10 months, and the mean time on therapy was 8.4 ± 4.4 (median 7; range 2-18) years. The time from the appearance of the first symptom to diagnosis was 8.1 ± 14.2 (range 0-52) years. At the time of starting therapy, 5.4 % of patients had an estimated glomerular filtration rate of60 ml/min, 67.6 % had proteinuria and 27.0 % had microalbuminuria. Therapeutic strategies included angiotensin-converting enzymer inhibitors (97.1 %), angiotensin receptor antagonists (1 patient), dual therapy (11.8 %) and statins (8.8 %). Among patients included in the prospective dataset, prevented the need for dialysis. Among new patients, no patient at risk for renal failure progressed to the next disease stage after 4 years follow-up; three patients even regressed to a lower stage during therapy.Treatment with blockers of the renin-angiotensin-aldosterone system prevents progressive renal failure in AS patients with heterozygous mutations in the genes causing AS. Considerable numbers of aging AS patients on dialysis may have heterozygous mutations in these genes (present in 1 % of total population) as underlying disease. Hence, greater alertness towards timely diagnosis and therapy has the potential to prevent progressive renal failure in most-if not all-AS patients with heterozygous mutations in the causal genes.

In the literature of recent years there are few publications on the importance of research in electron-microscopic pathomorphological diagnosis of kidney disease. The most important, which is diagnosed only on the basis of these studies are: minimal change disease, assessment of mesangial cell proliferation as well as the differentiation of the types of membranoproliferative glomerulonephritis, fibrillary glomerulonephritis, lupus nephritis, thin basement membrane disease, Alport syndrome, hemolytic-uremic syndrome. This report presents the most characteristic features of the ultrastructure allowing for diagnosis of these diseases.

Based on their studies and the data available in the literature, the authors consider current views on hereditary nephropathies running with hematuria, such as Alport syndrome, thin basement membrane disease, C3 glomerulonephritis, etc.).

Thin basement membrane disease is more common than IgA nephropathy or Alport syndrome, which are also associated with the presence of erythrocyturia. Very few reports on the disorder are available in the Polish literature. The objective of this work was to analyze the results from 83 patients with thin basement membrane syndrome as well as to formulate a proposal of strict morphological assessment criteria for the disorder. Attention was drawn to the requirement of thickness of the lamina densa rather than the entire basement membrane thickness and a sufficiently high number of loops featuring thinned lamina densa, namely at least 80% of loops, being taken into account. Occurrence of other morphological changes associated with the disorder and clinical symptoms other than erythrocyturia was also highlighted.

Introduction: Hereditary nephritis is an umbrella term for a group of congenital childhood diseases including but not limited to Alport syndrome, thin basement membrane disease, and Fabry disease. Objectives: The purpose of this study was a clinicopathologic investigation of Alport syndrome, thin basement membrane disease, and Fabry disease with a focus on the role of electron microscopy and toluidine blue staining in diagnosis. Patients and Methods: In this cross-sectional study, we investigated kidney biopsies with a final diagnosis of either Alport syndrome, thin basement membrane disease or Fabry disease from 2001 to 2016. Electron microscopy and light microscopy were done and the clinical and paraclinical data were extracted from the patients’ medical charts. Electron microscopy role was assessed in terms of necessary, helpful or non-necessary, while correlations between clinical and para-clinical data were determined using appropriate statistical tests. Results: Among the 2865 kidney biopsies, there were 22 patients of hereditary nephritis including 15 (0.52%) Alport syndrome, 5 (0.17%) thin basement membrane disease and 2 (0.07%) Fabry disease diagnosed by electron microscopy. Electron microscopy was essential for the diagnosis of 19 (86.4%) cases, helpful for 3(13.6%) and there was no case for which electron microscopy was non-necessary. The patients’ mean age was 16.1 ± 9.0 years. The most common finding in Alport syndrome was proteinuria (86.7%) followed by hematuria (60.0%). Conclusion: Considering the rate of misdiagnosis of hereditary nephritis using light microscopy and clinical findings alone, electron microscopy study and toluidine blue staining has an essential role in the precise diagnosis in these patients. With regard to the progressive nature of these diseases, prompt diagnosis using electron microscopy is pertinent for therapeutic decisions.

Background Although the renal toxicity of Deferasirox, an oral iron chelator, has been reported to be mild, there have been reports of acute interstitial nephritis or Fanconi syndrome due to this agent. Thin basement membrane disease (TBMD) is a hereditary disease characterized primarily by hematuria, with gross hematuria also observed in about 7% of cases. We herein report a case of TBMD that presented with acute kidney injury and gross hematuria during treatment with Deferasirox. Case presentation The patient was a 63-year-old man who had been diagnosed with myelodysplastic syndrome 6 years ago. He had started taking Deferasirox at 125 mg due to post-transfusion iron overload 6 months ago. Deferasirox was then increased to 1000 mg three months ago. When the serum creatinine level increased, Deferasirox was reduced to 500 mg three weeks before hospitalization. Although the serum creatinine level decreased once, he developed a fever and macroscopic hematuria one week before hospitalization. The serum creatinine level increased again, and Deferasirox was stopped four days before hospitalization. He was admitted for the evaluation of acute kidney injury and gross hematuria. Treatment with temporary hemodialysis was required, and a kidney biopsy was performed on the eighth day of admission. Although there was no major abnormality in the glomeruli, the leakage of red blood cells into the Bowman’s space was observed. Erythrocyte cast formation was observed in the tubular lumen, which was associated with acute tubular necrosis. The results of an electron microscopic study were compatible with TBMD. Conclusion Although Deferasirox is known to be nephrotoxic, gross hematuria is relatively rare. When we encounter a case of acute kidney injury with gross hematuria during treatment with Deferasirox, TBMD should be considered as a possible cause of gross hematuria.

Aim It has been reported that the innate immune system plays a pivotal role in the pathogenesis of immunoglobulin A nephropathy (IgAN). To explore non-invasive monitoring of disease activity in children with IgAN, we examined whether expressions of mRNA for innate immunity-associated functional molecules: CC ligand chemokine 5 (CCL5), fractalkine/CX3CL1, interferon-γ-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), retinoic acid-inducible gene-I (RIG-I), and toll-like receptor 3 (TLR3) in urinary sediment from patients with IgAN correlate with histologic parameters. Methods Twenty consecutive children with IgAN and four children with thin basement membrane disease (serving as a non-inflammatory control) were enrolled in this pilot study. Urinary mRNA expressions of target genes were examined real-time quantitative polymerase chain reaction. Results The expressions of CCL5, fractalkine and RIG-I were significantly increased in IgAN (all P

Background Hereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts. Methods We used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses. Results We identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested. Conclusions Missense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans.