Periostin Attenuates Cyclophosphamide-induced Bladder Injury by Promoting Urothelial Stem Cell Proliferation and Macrophage Polarization.

Interstitial cystitis (IC) is a bladder syndrome of unclear etiology with no generally accepted treatment. Growing evidence suggest that periostin (POSTN) is an important homeostatic component in the tissue repair and regeneration in adulthood, but its function in urinary bladder regeneration is still unknown. Here we investigate whether POSTN is involved in bladder tissue repair in a cyclophosphamide (CYP)-induced interstitial cystitis model. POSTN is primarily expressed in bladder stroma (detrusor smooth muscle and lamina propria) and upregulated in response to CYP-induced injury. POSTN deficiency resulted in more severe hematuria, aggravated edema of the bladder, and delayed umbrella cell recovery. Besides, less proliferative urothelial cells (labeled by pHH3, Ki67, and EdU) and lower expression of Krt14 (a urothelial stem cell marker) were detected in POSTN-/- mice post CYP exposure, indicating a limited urothelial regeneration. Further investigations revealed that POSTN could induce Wnt4 upregulation and activate AKT signaling, which together activates ß-catenin signaling to drive urothelial stem cell proliferation. In addition, POSTN can promote resident macrophage proliferation and polarization to a pro-regenerative (M2) phenotype, which favors urothelial regeneration. Furthermore, we generated injectable P-GelMA granular hydrogel as a biomaterial carrier to deliver recombinant POSTN into the bladder, which could increase urothelial stem cells number, decrease umbrella cells exfoliation, and hence alleviate hematuria in a CYP-induced interstitial cystitis model. In summary, our findings identify a pivotal role of POSTN in bladder urothelial regeneration and suggest that intravesical biomaterials-assisted POSTN delivery may be an efficacious treatment for interstitial cystitis.

Prognosis and acute complications at the first onset of idiopathic nephrotic syndrome in children: a nationwide survey in Japan (JP-SHINE study).

BACKGROUND: Information on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce. METHODS: The Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients' prognosis in this cohort. RESULTS: We obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8-9.4] and a median follow-up period of 4.1 years (IQR 2.5-5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin <1.0 g/dL) and severe bacterial infection were not independent factors, but female sex {hazard ratio [HR] 1.5 [95% confidence interval (CI) 1.1-1.7]} and hypertension [HR 4.0 (95% CI 2.6-6.0)] were significantly related to AKI. During the observation period, ocular hypertension requiring treatment occurred in 17.4% of patients, among which 0.4% received surgical treatment. Progression to frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome in 3 years was seen in 44.2% of the patients and was shown by the Cox regression analysis to be significantly related to younger age and days until remission at the first episode, but not to sex, hematuria, the minimum serum albumin level or AKI. Two patients died during the observation period. One patient showed progression to end-stage kidney disease. CONCLUSION: Based on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.

Immunoglobulin-Negative DNAJB9-Associated Fibrillary Glomerulonephritis: A Report of 9 Cases.

Fibrillary glomerulonephritis (FGN) was previously defined by glomerular deposition of haphazardly oriented fibrils that stain with antisera to immunoglobulins but do not stain with Congo red. We report what is to our knowledge the first series of immunoglobulin-negative FGN, consisting of 9 adults (7 women and 2 men) with a mean age at diagnosis of 66 years. Patients presented with proteinuria (100%; mean protein excretion, 3g/d), hematuria (100%), and elevated serum creatinine level (100%). Comorbid conditions included carcinoma in 3 and hepatitis C virus infection in 2; no patient had hypocomplementemia or monoclonal gammopathy. Histologically, glomeruli were positive for DNAJB9, showed mostly mild mesangial hypercellularity and/or sclerosis, and were negative for immunoglobulins by immunofluorescence on frozen and paraffin tissue. Ultrastructurally, randomly oriented fibrils measuring 13 to 20nm in diameter were seen intermingling with mesangial matrix in all and infiltrating glomerular basement membranes in 5. On follow-up (mean duration, 21 months), 2 had disease remission, 4 had persistently elevated serum creatinine levels and proteinuria, and 3 required kidney replacement therapy. Thus, rare cases of FGN are not associated with glomerular immunoglobulin deposition, and the diagnosis of FGN in these cases can be confirmed by DNAJB9 immunostaining. Pathogenesis remains to be elucidated.

A case report of a young girl with recurrent hematuria: a missed diagnosis - renal nutcracker syndrome.

BACKGROUND: Nutcracker syndrome is an easily missed cause of hematuria in children. It is characterized by left renal vein entrapment between the abdominal aorta and the superior mesenteric artery causing renal venous hypertension. Intermittent hematuria and orthostatic proteinuria with or without abdominal or flank pain are the common clinical manifestations. Presence of variable non-specific symptoms and non-significant physical findings results in a delayed diagnosis. CASE PRESENTATION: We present a ten -year -old girl with four episodes of painless gross hematuria and recurrent microscopic hematuria since the age of two years. Doppler ultrasound showed left renal vein compression while 3 D computerized tomography angiography confirmed the diagnosis of an anterior nutcracker. The patient was conservatively treated with nutritional support (pediasure complete formula and high calorie food), iron supplements and followed up, monitored for anemia, hypertension and renal insufficiency. CONCLUSION: Nutcracker syndrome is a rare cause of recurrent gross hematuria in children. A high index of suspicion and proper imaging is needed to reach a proper diagnosis and avoid the psychological and financial stress on the family.

Urinary metabolic abnormalities in children with idiopathic hematuria.

BACKGROUND: Hematuria, either macroscopic or microscopic, is an incidental finding of multiple nephrologic or urologic disorders. Disturbances of urine inhibitors or promotors have been suggested as the potential causes of isolated idiopathic hematuria in children and its recurrence. Meanwhile, appropriate treatment of these risk factors might improve secondary asymptomatic or macroscopic hematuria. OBJECTIVES: The aim of this study was to identify contribution of urinary biochemical abnormalities in children with isolated idiopathic hematuria. METHODS: About 522 children with isolated hematuria were evaluated in a prospective cross-sectional study. Data such as clinical manifestations, family history, laboratory examinations, structural anomalies, and urine biochemistry were obtained. Patients with nephrolithiasis, nephrocalcinosis, tubulointerstitial disorder, genitourinary abnormality, urinary tract infection, and glomerular disorder were excluded from the study. Variables such as calcium, citrate, oxalate, phosphate, uric acid, cystine, and magnesium were measured in 24-h urine collection. In addition, serum levels of electrolytes, urea, creatinine, parathyroid hormone, and bicarbonate were identified. RESULTS: Mean age at diagnosis was 5.9 years, and females outnumbered males (2/1). Of those, 88.5% had microscopic hematuria, and 12.6% experienced episodes of gross hematuria. Abdominal pain was the most common clinical manifestations. Urinary tract infection occurred in 30% of cases. Totally, 94% of patients had single or multiple metabolic abnormalities in 24-h urine excretion including hypocitraturia, 60.7%; hypomagnesuria, 58.2%; hyperuricosuria, 35.8%; hypercalciuria, 33.7%; hyperoxaluria, 33.7%; and cystinuria, 0.76%, respectively. About 8% of cases had mixed urine metabolic disturbances. Most patients had mild hematuria (red blood cell <10/high power field (hpf)), and 18% had significant hematuria (>30/hpf), with no statistical correlation to urine metabolic abnormalities. About 80% of patients had a history of nephrolithiasis in their relatives. DISCUSSION: Decreased urinary inhibitor concentration followed by increased stimulator concentration were the most common abnormalities in patients with idiopathic hematuria. Accordingly, measurement of urinary biochemical concentration is highly recommended in children with isolated hematuria. In addition, investigating the therapeutic effect of potassium citrate supplements is highly recommended in these patients to prevent future stone formation and treatment of hematuria.

Activated natural killer T cells in mice induce acute kidney injury with hematuria through possibly common mechanisms shared by human CD56+ T cells.

Although activation of mouse natural killer T (NKT) cells by α-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, the precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. The perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas the TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells. Kidney injury in young mice was mild but could be significantly exacerbated if NKT cells were strongly activated by NK cell depletion alone or in combination with IL-12 pretreatment. When stimulated by a combination of IL-2 and IL-12, human CD56+ T cells, a functional counterpart of mouse NKT cells, also damaged both glomerular endothelial cells and tubular epithelial cells, with the former being affected in a perforin-dependent manner. These data suggest that both mouse NKT cells and human CD56+ T cells are integral to the processes that mediate AKI. Targeting CD56+ T cells may, therefore, be a promising approach to treat AKI.

Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes.

Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.

Hypocomplementemic Urticarial Vasculitis Syndrome With Crescentic Glomerulonephritis.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up.

Neuropilin1 regulates glomerular function and basement membrane composition through pericytes in the mouse kidney.

Neuropilin1 (Nrp1) is a co-receptor best known to regulate the development of endothelial cells and is a target of anticancer therapies. However, its role in other vascular cells including pericytes is emergent. The kidney is an organ with high pericyte density and cancer patients develop severe proteinuria following administration of NRP1B-neutralizing antibody combined with bevacizumab. Therefore, we investigated whether Nrp1 regulates glomerular capillary integrity after completion of renal development using two mouse models; tamoxifen-inducible NG2Cre to delete Nrp1 specifically in pericytes and administration of Nrp1-neutralizing antibodies. Specific Nrp1 deletion in pericytes did not affect pericyte number but mutant mice developed hematuria with glomerular basement membrane defects. Despite foot process effacement, albuminuria was absent and expression of podocyte proteins remained unchanged upon Nrp1 deletion. Additionally, these mice displayed dilation of the afferent arteriole and glomerular capillaries leading to glomerular hyperfiltration. Nidogen-1 mRNA was downregulated and collagen4α3 mRNA was upregulated with no significant effect on the expression of other basement membrane genes in the mutant mice. These features were phenocopied by treating wild-type mice with Nrp1-neutralizing antibodies. Thus, our results reveal a postdevelopmental role of Nrp1 in renal pericytes as an important regulator of glomerular basement membrane integrity. Furthermore, our study offers novel mechanistic insights into renal side effects of Nrp1 targeting cancer therapies.

Plasma and urine DNA levels are related to microscopic hematuria in patients with bladder urothelial carcinoma.

a) Objective: An increase in cell-free DNA was observed in the plasma of many cancer patients. This major biomarker can be used to differentiate patients with malignant neoplasms from those with benign neoplasms or healthy patients. Depending on the characteristic of the tumor, there are qualitative variations in the circulating cell-free DNA. Today, studies on the concentration of fragments of circulating cell-free DNA and their respective sizes in patients with bladder cancer are not plentiful in the literature. A 100% effective plasma tumor marker, which would help in the diagnosis and follow-up of bladder cancer, is yet to be developed; therefore, cell-free DNA levels in the plasma may represent a valuable biomarker for the diagnosis, prognosis and follow-up of patients with this type of tumor. b) Design and methods: In this study we analyze the kinetics of plasma and urine DNA concentrations in patients with bladder cancer, relating them to the other clinical laboratory variables. c) Results: Patients with hematuria showed a positive correlation with urine DNA. d) Conclusion: An increase in plasma and urine DNA was unprecedentedly reported over time, a fact that may come in handy in the prognosis of patients. Furthermore, microscopic haematuria is correlated with plasma and urinary DNA levels.

Metabolic risk factors in children with asymptomatic hematuria.

BACKGROUND: Idiopathic or benign hematuria is diagnosed in children after all other possible causes have been ruled out and test results for renal or urologic pathologies are negative. METHODS: To identify possible urinary risk factors for hematuria in children, we retrospectively evaluated clinical onset, family history, and metabolic risk factors of 60 children with idiopathic hematuria but without renal stones or other pathologic conditions that could explain the hematuria. All patients followed the same ambulatory protocol at that used to evaluate kidney stone-formers. RESULTS: Seven patients had microhematuria, three patients each had microhematuria and gross hematuria, and the remaining 50 patients had gross hematuria onset. A family history of stone disease was found in 63 % of the children. At least one urinary metabolic abnormality was present in 49 patients, while 11 patients had no metabolic abnormality. The most common urinary risk factor was idiopathic hypercalciuria (single or associated), which was found in 43.5 % of patients, followed by hypocitraturia (single or associated), present in 31.7 %. Unduly acidic urine pH as a single abnormality was found in 10 % of this pediatric patient population. We also found hyperoxaluria and, less frequently, hypomagnesuria, and hyperuricosuria. CONCLUSIONS: Asymptomatic idiopathic hematuria in pediatric patients may often be associated to different urinary biochemical abnormalities, similar to what is observed in pediatric kidney stone-formers.

Absence of mesangial C1q deposition is associated with resolution of proteinuria and hematuria after tonsillectomy plus steroid pulse therapy for immunoglobulin a nephropathy.

INTRODUCTION AND AIMS: Deposition of C1q occurs in 0 to 45% of patients with IgAN. In order to identify whether mesangial C1q deposition in IgAN is a novel marker for the response to tonsillectomy plus steroid pulse therapy (TSP), we studied the association between mesangial C1q deposition in IgAN and the remission rate after TSP therapy for IgAN. METHODS: We conducted a retrospective cohort study at a single Japanese center. We analyzed data on 110 patients diagnosed with IgA nephropathy who received TSP between January 2003 and December 2012. Positive C1q findings were defined as diffuse mesangial C1q deposition. The study outcome was the resolution of abnormal urinary findings and was defined as negative proteinuria and negative occult blood 1 year after steroid pulse therapy. RESULTS: In all enrolled cases, 69 patients (62.7%) went into remission. Ten out of 24 (41.7%) C1q-positive patients experienced remission, and 59 out of 86 (68.6%) C1q-negative patients experienced remission. Multiple logistic regression model analysis showed that the absence of C1q deposition increased the odds ratio for remission (odds ratio 4.41; 95% confidence interval 1.33-15.75, p = 0.017). CONCLUSIONS: These results suggest that the absence of diffuse C1q deposition in the mesangial area of the glomerulus in patients with IgA nephropathy is a positive predictive sign for a response to TSP and is associated with the resolution of urinary abnormalities 1 year after TSP.

Infarto de nervio óptico asociado a síndrome de Sneddon / Optic nerve infarction in Sneddon's syndrome

CASO CLÍNICO: Se expone el caso de una mujer de 26 años con fenómeno de Raynaud y livedo reticularis de 2 años de evolución que se presentó con alteraciones del campo visual acompañadas de hipertensión arterial, hematuria y cefalea. En la exploración se objetivaron múltiples infartos retinianos y de cabeza del nervio óptico bilateral. DISCUSIÓN: El síndrome de Sneddon es una vasculitis que cursa con livedo reticularis, clinica neurológica y, menos frecuentemente, con infartos de miocardio, renales y retinianos. Revisando la literatura podemos decir que se trata del primer caso de síndrome de Sneddon descrito que se inició con infartos del nervio óptico

CLINICAL CASE: We report a case of a 26 year old woman with Raynaud's phenomenon and livedo reticularis 2 years onset, who presented with visual field defects accompanied by hypertension, hematuria, and headache. The examination revealed multiple retinal and optic nerve head infarcts in both eyes. DISCUSSION: Sneddon's syndrome is a vasculitis that produces livedo reticularis, neurological symptoms, and less frequently myocardial, renal and retinal infarction. After reviewing the literature, this is the first case described of Sneddon's syndrome presenting with optic nerve infarction

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Protective effects of lipoic acid and mesna on cyclophosphamide-induced haemorrhagic cystitis in mice.

The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.

The use of molecular analyses in voided urine for the assessment of patients with hematuria.

INTRODUCTION: Patients presenting with painless hematuria form a large part of the urological patient population. In many cases, especially in younger patients, the cause of hematuria is harmless. Nonetheless, hematuria could be a symptom of malignant disease and hence most patients will be subject to cystoscopy. In this study, we aimed to develop a prediction model based on methylation markers in combination with clinical variables, in order to stratify patients with high risk for bladder cancer. MATERIAL AND METHODS: Patients (n=169) presenting with painless hematuria were included. 54 patients were diagnosed with bladder cancer. In the remaining 115 patients, the cause of hematuria was non-malignant. Urine samples were collected prior to cystoscopy. Urine DNA was analyzed for methylation of OSR1, SIM2, OTX1, MEIS1 and ONECUT2. Methylation percentages were calculated and were combined with clinical variables into a logistic regression model. RESULTS: Logistic regression analysis based on the five methylation markers, age, gender and type of hematuria resulted in an area under the curve (AUC) of 0.88 and an optimism corrected AUC of 0.84 after internal validation by bootstrapping. Using a cut-off value of 0.307 allowed stratification of patients in a low-risk and high-risk group, resulting in a sensitivity of 82% (44/54) and a specificity of 82% (94/115). Most aggressive tumors were found in patients in the high-risk group. The addition of cytology to the prediction model, improved the AUC from 0.88 to 0.89, with a sensitivity and specificity of 85% (39/46) and 87% (80/92), retrospectively. CONCLUSIONS: This newly developed prediction model could be a helpful tool in risk stratification of patients presenting with painless hematuria. Accurate risk prediction might result in less extensive examination of low risk patients and thereby, reducing patient burden and costs. Further validation in a large prospective patient cohort is necessary to prove the true clinical value of this model.

Temporal and spatial expression of podocyte-associated molecules are accompanied by proteinuria in IgA nephropathy rat model.

We used a rat model to assess the role of nephrin, podocin, and desmin in the pathogenesis of IgA nephropathy (IgAN). A rat IgAN model was established by administration of BSA, CCl(4), and lipopolysaccharide (LPS) and compared with healthy control rats. Urinary protein, urine red blood cells, and biochemical parameters were measured for 12 weeks. Renal morphology and ultrastructure were examined by light and electron microscopy. Immunofluorescence was used to assess IgA deposition in the glomeruli and to measure expression of nephrin, podocin, and desmin. Real-time quantitative PCR was used to measure expression of nephrin, podocin, and desmin mRNAs. IgAN rats developed proteinuria at week-6 and this worsened over time. Pathological changes were evident under light microscopy at week-8 and under electron microscopy at week-4. Immunofluorescence analysis showed deposition of IgA in the kidneys of IgAN rats, but not control rats. IgAN rats had increased expression of glomerular podocin, nephrin, and desmin mRNAs and proteins at week-4. The expression of nephrin, podocin and desmin proteins and the expression of podocin and desmin mRNAs preceded the increase in urinary protein. Taken together, our study of a rat model of IgAN indicates that changes in the expression and distribution of nephrin, podocin, and desmin precede and may cause foot process fusion and proteinuria.

Unusual presentations of BK virus infections in pediatric renal transplant recipients.

BKV has emerged as a significant pathogen in the field of transplantation, predominantly causing BKV nephropathy in renal transplant recipients and hemorrhagic cystitis in HSCT recipients. However, case reports describe more diverse complications, and we too present three unusual cases of BKV infections in pediatric renal transplant recipients. First, we describe a case of biopsy-proven renal damage secondary to BKV prior to the onset of viremia, demonstrating that BKV nephropathy can occur without preceding viremia. We also present two renal transplant recipients with persistent BK viruria, one with BKV-associated hemorrhagic cystitis and the other with microscopic hematuria. Therefore, we conclude that BKV manifestations may be more diverse than previously thought and suggest clinical utility in urine BKV qPCR testing in specific transplant recipients.

Mesangial IgA deposits indicate pathogenesis of anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (anti-GBM) disease is characterized by crescentic glomerulonephritis with immunoglobulin G (IgG) autoantibodies to the non-collagenous (NC1) domain of α3(IV) collagen presenting along the GBM. The patient clinically manifests with rapidly progressive glomerulonephritis (RPGN) with pulmonary hemorrhage (Goodpasture syndrome). In rare cases, other immunocomplexes of IgA or IgM are involved, but their specificities have not been determined. We report a rare case of a 31-year-old female who was diagnosed as having anti-GBM disease with extensive IgA deposits in the mesangium. This patient presented heavy hematuria, proteinuria with increasing creatinine, but no lung hemorrhage. Renal biopsy showed crescentic glomerulonephritis (type Ⅰ) with strong IgA (3+) as lump and branch shape. Therapies with pulse methylprednisolone, plasmapheresis and cyclophosphamide administration were less effective. This case is different from the present type Ⅰ crescentic glomerulonephritis and the specificity of IgA deposits may implicate the pathogenesis of anti-GBM disease.