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Podocytic infolding glomerulopathy (PIG) is a rare glomerular abnormality involving glomerular basement membrane (GBM) bubbling viewable by light microscopy, extensive invagination of the podocytic cytoplasm, and the presence of microstructures viewable by electron microscopy. PIG was proposed as a new disease entity in 2008. However, cases have been reported exclusively in Japan and no case reports outside Japan have been published. Here, we report a case of PIG in a 44-year-old Korean female. The patient showed mild proteinuria without renal functional impairment or other systemic diseases. Glomeruli were normocellular, but GBMs were diffusely and mildly thickened and showed a bubbly appearance with periodic acid methenamine silver (PAMS) staining. Immunofluorescence microscopy showed minimal mesangial IgM deposition, but staining was negative for IgG, IgA, C3, C4, C1q, and fibrinogen. Electron microscopy showed diffuse distribution of microtubules and microspherules within thickened GBM (620–1180 nm). Additional serologic tests revealed positive antinuclear antibodies, but other autoimmune markers were normal or negative. The patient was treated with steroids for three months, after which proteinuria decreased to the normal range. [ABSTRACT FROM PUBLISHER]

Objective: To analyze the factors indicating renal injury in patients with bilateral ureteropelvic-junction obstruction (UPJO). Methods: We investigated 26 patients, 35 kidney units (KUs), who were diagnosed with bilateral UPJO and underwent unilateral or bilateral pyeloplasty between January 2000 and December 2011. During pyeloplasty, ipsilateral kidney biopsy was performed. Kidney biopsy results were divided into 3 categories. Hydronephrosis was analyzed using both the Society of Fetal Urology (SFU) and Onen''s grading system. We investigated factors related with the renal histopathologic results of 29 KUs. We additionally analyzed whether there were factors predicting contralateral pyeloplasty after initial unilateral pyeloplasty. Results: Ten KUs (34.5%) showed grade 1 histopathologic change, whereas 10 KUs (34.5%) and 9 KUs (31.0%) showed grade 2 and 3 change, respectively. Preoperative differential renal function (DRF) and serum creatinine levels were not different among groups (P = .697 and .516, respectively). Hydronephrosis grade was not different when graded by SFU system (P = .100) while significantly different by Onen''s system (P <.001). Among 23 patients with initial unilateral pyeloplasty, additional contralateral pyeloplasty was required in 6 patients (26.1%). There were no significant preoperative factors predicting the need for additional operations. Conclusion: In bilateral UPJO, DRF, and SFU grade of hydronephrosis did not correctly reflect renal injury. Onen''s hydronephrosis grade showed a significant relationship with renal histopathologic grade and could be an indicator for renal injury in bilateral UPJO. [Copyright &y& Elsevier]

Information is limited regarding the histological features related to chronic graft dysfunction and failure in patients with IgA nephropathy developing after renal transplantation. The prevalence and significance of glomerular crescents in post-transplant IgAN including recurrent,de novoand transmitted forms (TxIgAN), were studied. Renal morphology was evaluated in 71 patients of TxIgAN, obtained at more than 6 months post-transplant, and compared with regard to the presence (C-TxIgAN) or absence (N-TxIgAN) of glomerular crescents. Crescents were demonstrated in 12 samples of 10 patients (14.1%). The percentages of crescents were from 4.8% to 83.3% (median, 28.6%) in each sample. Ten samples of C-TxIgAN had cellular to fibrocellular crescents, and four of these were associated with diffuse mesangial proliferation. Serum creatinine levels and the frequency of nephrotic range proteinuria at the time of biopsy and the degree of interstitial inflammation were significantly different in the two groups. Graft survival after allograft biopsies was significantly lower in C-TxIgAN (P = 0.0017). Chronic rejection was a major cause of graft loss in N-TxIgAN (31.8%), whereas TxIgAN was the major cause in C-TxIgAN (66.7%). In conclusion, the current study suggests that glomerular crescents are not rare and that they are responsible for chronic graft dysfunction in TxIgAN patients. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril. Materials and methods: Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology. Results: No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of ≥1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance. Conclusions: Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes. [ABSTRACT FROM AUTHOR]

SUMMARY: The long-term outcome was evaluated, in terms of recurrence and graft survival, after live donor renal transplantation in 90 grafts in 89 patients with biopsy-proven IgA nephropathy (IgAN) as a primary diagnosis of end-stage renal disease. Additionally, histological assessment including glomerular morphometry was performed in 19 grafts having recurrent IgAN. The 10-year graft survival for IgAN patients was 66%, which was comparable with that of 84% for 107 reference recipients having other kinds of glomerulonephritis (GN) or 69% for 90 other recipients having non-GN renal failure (P = 0.27). In 43 grafts, 54 event graft biopsies were performed, and mesangial IgA deposits were documented in 19 grafts. In eight grafts, lesions were accompanied by chronic rejection (CR). Ten-year cumulative recurrence was 44%. In total, 10 grafts were lost: this was due to CR (n = 3) or acute rejection (n = 1) in 24 recurrence-free recipients; CR (n = 2) or recurrence (n = 2) in 19 patients with recurrence; and patient death (n = 2) in 46 patients who did not have graft biopsy. No difference in 10-year graft survival between the patients with and without recurrence (63%vs 74%; P = 0.98), or the proportion of related donors was found (68%vs 83%; P = 0.25). In the grafts with recurrence, renal histological damage was relatively mild and had no uniform pattern. The percentage of global and segmental sclerosis were 11.9% and 3.7%, respectively. Non-sclerotic glomeruli were ischaemic or hypertrophied. Mesangium showed lysis or focal and mild expansion by matrix and cellular increase. Glomerular morphometry was performed in seven patients, in whom glomerular hypertrophy was found as demonstrated by increases of Bowman's and glomerular tuft areas (1.4 and 1.3 times the control, respectively) and concomitant decrease of total glomerular and mesangial cells per glomerular cross-section (71.2% and 84.9% of the control, respectively). In conclusion, recurrence increased to 44% with... [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs. [ABSTRACT FROM AUTHOR]

Background Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. Methods This nested case–control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. Results A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P  <  0.001). In the nested case–control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30–0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. Conclusions Bisphosphonates may improve long-term graft survival in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. Methods We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. Results Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1–2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1–2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1–2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. Conclusions Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy. [ABSTRACT FROM AUTHOR]

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and renal involvement (HSP nephritis, HSPN) is a severe manifestation. HSPN is histologically classified by the International Study of Kidney Disease in Children (ISKDC) based on mesangial hypercellularity and the extent of glomerular crescents. Macrophages, categorized as M1 or M2, frequently infiltrate in various glomerular and tubulointerstitial diseases and infiltration of specific subtypes is associated with disease progression. Therefore, to identify whether infiltration of M1 or M2 macrophages has clinical significance, we quantified the subtypes of macrophages in 49 HSPN specimens and correlated the counts with histologic features and clinical parameters. Higher tubulointerstitial M2 counts were associated with chronic renal failure (CRF), ISKDC classes III-IV, and crescents (P<0.001, 0.002, 0.001). Glomerular M2 counts were significantly related to ISKDC classes III-IV and crescents (area under curve, AUC 0.804, 0.833). Tubulointerstitial M2 counts were associated with CRF, ISKDC classes III-IV, and crescents (AUC 0.872, 0.778, 0.830). Tubulointerstitial M2 counts also revealed higher AUC than tubulointerstitial M1 counts for CRF (P=0.036) and ISKDC classes III-IV (P=0.047). Glomerular M2 counts revealed higher AUC than glomerular M1 counts for ISKDC classes III–IV (P=0.024). Tubulointerstitial M2 counts were the most powerful parameter for CRF (AUC 0.872) and revealed even higher AUC than ISKDC classification (AUC 0.716) with borderline significance (P=0.086) for CRF. In summary, tubulointerstitial M2 counts were a superior parameter to tubulointerstitial M1 counts and even to ISKDC classification indicating the presence of CRF. [ABSTRACT FROM AUTHOR]

Background Tubuloreticular inclusions (TRIs) are anastomosing networks of microtubules that are frequently found in autoimmune diseases and viral infections. In renal allografts, TRIs have been reported in glomerular endothelial cells in association with viral infections and donor specific antibodies (DSAs), but their presence in peritubular capillaries has not been explored. Methods We collected seven cases with TRIs out of 148 consecutive renal allograft biopsies taken from Dec. 2015 to Dec. 2016. Results TRIs were present in peritubular capillaries in seven cases and were concomitantly present in glomerular endothelial cells in two cases. The diagnoses included polyomavirus nephropathy (n = 2), acute T cell-mediated rejection (ACR) (n = 1), combined ACR and antibody-mediated rejection (AMR) (n = 1), suspicious for ACR (n = 1), chronic active AMR (n = 1), and moderate tubular atrophy and interstitial fibrosis (n = 1). Six patients had recent or current viral infections (BK polyomavirus, hepatitis B virus, herpes simplex virus, and cytomegalovirus in two, two, one, and one case, respectively). DSA was positive in one case. Five cases had moderate to severe interstitial inflammation and four cases had peritubular capillaritis. Conclusion TRIs are not rare in peritubular capillaries. They are associated with various viral infections and their appearance seems to be related to peritubular capillary injury. [ABSTRACT FROM AUTHOR]

Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated LOXL2 and tubulointerstitial fibrosis. The present study evaluated the effect of LOXL2 inhibition using an inhibitory monoclonal antibody (AB0023) on tubulointerstitial fibrosis in a folic acid-induced tubulointerstitial fibrosis mouse model. The association of LOXL2 with epithelial-mesenchymal transformation-related molecules was also evaluated in vitro using HK-2 cells. The present data demonstrated that AB0023 prevented the progression of tubulointerstitial fibrosis significantly, as determined by trichrome and picro-sirius red staining, as well as the total collagen assay. The mean expression of phosphorylated Smad2 and Smad4 was lower in the AB0023-treated group although it was not statistically significant. Following transforming growth factor-β (TGF-β) challenge, LOXL2-deficient HK-2 cells exhibited significantly lower expression of the mesenchymal markers vimentin and fibronectin than control HK-2 cells. In conclusion, LOXL2 inhibition ameliorates renal fibrosis through the TGF-β/Smad signalling pathway. [ABSTRACT FROM AUTHOR]

The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change. We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria. According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases. The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase. • The diagnostic criteria for ABMR has been changed significantly. • The microvascular inflammation is the most frequent histology in C4d-negative ABMR. [ABSTRACT FROM AUTHOR]

C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case ofde novoC3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident. [ABSTRACT FROM PUBLISHER]

Background: Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown. Methods: We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR. Results: During a median follow-up duration of 65 (12–154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3–0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0–2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0–2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3–0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (−0.41±1.68 vs. −0.73±2.82 ml/min/1.73 m2/year, P = 0.03). Conclusion: In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3–0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN. [ABSTRACT FROM AUTHOR]

Background To date, there has been much controversy about the role of crescentic lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN). This study evaluated whether crescentic lesions predict adverse renal outcomes in IgAN patients. Methods A total of 430 patients with biopsy-proven IgAN between January 2000 and December 2009 were included. Histological variables of the Oxford classification (Oxford-MEST) and the presence of crescents were assessed. The primary endpoint was a 50% decline in estimated glomerular filtration rate. Results Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with crescents compared with 40 (11.5%) patients without crescents (P = 0.01). A Kaplan–Meier plot showed that the 10-year renal survival rate was significantly lower in patients with crescents than patients without crescents (P = 0.01). However, in a multivariable Cox analysis which included clinical factors and the Oxford-MEST, crescents were not significantly associated with an increased risk of developing the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36–1.41, P = 0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the discriminative ability for the prediction of renal outcomes [c-statistic: 0.86 (0.81–0.91) vs. 0.86 (0.80–0.91), P = 0.21]. Conclusion Crescentic lesion was not an independent prognostic factor, suggesting that crescents have limited value in predicting renal outcomes of IgAN. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the location of interstitial cells of Cajal-like cells and the ureteral aspect using histopathologic studies of obstructive and refluxing megaureters to reveal the different pathogenesis of megaureters in the human urinary tract. The underlying pathophysiology of obstructive megaureter and refluxing megaureter is poorly understood. Methods: The data from 14 patients with obstructive megaureter (7 boys and 7 girls), with a mean age of 12 months (range 2-84), and 9 patients with refluxing megaureter (7 boys and 2 girls), with a mean age of 11 months (range 4-24), were compared. We investigated the difference in the histopathologic aspects using Masson''s trichrome, terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (for apoptosis), and human c-kit antibody (CD117 for interstitial cells of Cajal-like cells) between the obstructive and refluxing megaureters. Results: The proportion of smooth muscle was significantly lower in segments of refluxing megaureter (32.04% ± 4.96%) than in the segments of obstructive megaureter (52.48% ± 3.46%; P < .01). The number of apoptotic cells was significantly increased in the obstructive megaureter (mean 1661 ± 135.1 cells) compared with the refluxing megaureter (mean 375.2 ± 65.14 cells; P < .0001). The number of c-kit positive cells was significantly lower in the refluxing megaureter (mean 83.60 ± 48.84 cells) than in the obstructive megaureter (mean 463.6 ± 100.4 cells; P < .05). Conclusions: The differences in the histopathologic aspects can provide information on the possible pathophysiology of obstructive and refluxing megaureters. Ureteral peristalsis can be affected by the increased myocyte apoptosis in the obstructive megaureter and by the decreased number of interstitial cells of Cajal-like cells and smooth muscle content in refluxing megaureters. Additional research is warranted to elucidate the exact pathophysiology. [Copyright &y& Elsevier]

Abstract: PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT−/− mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT+/− mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT+/− mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT+/− mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT+/− mice. Cardiomyocytes from PICOT+/− mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator. [Copyright &y& Elsevier]

Immune dysregulation, polyendocrinopathy, enteropathy, X-linked ( IPEX) syndrome ( OMIM 304790) is a rare hereditary disorder of the immune regulatory system caused by FOXP3 mutations. The clinical features of this syndrome include a wide spectrum of severe autoimmune diseases and renal involvement, mostly due to tubulointerstitial diseases, in some patients. Glomerulopathy of membranous nephropathy ( MN) and minimal change nephrotic syndrome ( MCNS), however, have also been reported. We encountered two children with IPEX syndrome from the same family. Interestingly, they had different glomerular lesions: one had MN and the other had MCNS. Herein we describe the cases of these siblings and review the possible mechanisms for the development of two different renal lesions. [ABSTRACT FROM AUTHOR]

We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value. [ABSTRACT FROM AUTHOR]

Background. Nephrotic syndrome (NS) is rarely associated with ovarian tumor. Only five cases of NS with pathologic diagnosis have been reported in patients with ovarian tumors. However, the association between minimal change disease (MCD) and ovarian tumor has not been previously reported.Case. A 55-year-old woman presented with abdominal mass and edema. Radiologic studies revealed a 10 × 10 × 11 cm-sized mass and multiple enlarged lymph nodes, suggesting a malignant ovarian tumor. Urinalysis showed heavy proteinuria (4+) with decreased serum albumin and increased cholesterol levels, suggesting NS. She underwent operation and renal biopsy. Histopathology of the mass and the kidney revealed papillary serous carcinoma of the ovary and MCD, respectively. Oral prednisolone and adjuvant chemotherapy resulted in remission of NS.Conclusion. We herein report a case of MCD associated with ovarian carcinoma. [Copyright &y& Elsevier]

Several experimental studies implicate uric acid in renal injury and fibrosis. The objective of this study was to examine the association between uric acid level and allograft fibrosis after kidney transplantation. 241 adult patients who underwent kidney transplantation between 2003 and 2014 were divided into three groups according to the sex specific tertiles of mean uric acid level within the first post-transplant year. The renal biopsies performed during 1 to 5 post-transplant year were analyzed to compare the degree of interstitial fibrosis and tubular atrophy (IF/TA). Mean interval between kidney transplantation and biopsy was similar between groups (23.7 ± 15.3 vs. 30.0 ± 18.6 vs. 27.5 ± 18.5 months, P = 0.072). The higher tertile uric acid level was, the more advanced grade of IF/TA was shown (P = 0.001). Multivariate analysis identified uric acid tertile was independent risk factor for severe IF/TA (odds ratio [95% confidence interval] was 3.16 [1.13-8.82] for tertile 2 and 3.70 [1.25-10.93] for tertile 3, versus tertile 1, respectively). Other independent factors were estimated glomerular filtration rate at 1year post-transplant (0.80 [CI 0.65-0.98]) and biopsy-proven rejection (2.34 [1.05-5.21]). Graft survival over 10 years was significantly lower in tertile 3 (P = 0.041). The results showed that higher uric acid level after kidney transplantation was associated with more severe IF/TA. [ABSTRACT FROM AUTHOR]