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Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Vijftig procent van de Nederlanders is te zwaar. De overheid wil dit percentage in 2040 terugdringen naar 38 procent. Dat staat in het Nationaal Preventieakkoord (NPA). Een van de afspraken is om het aantal calorieën in frisdranken in 2025 verlaagd te hebben met 30 procent. Nietalcoholische dranken leveren 24 procent van het toegevoegde suiker en 7 procent van de dagelijkse hoeveelheid energie die we binnenkrijgen. In diverse landen lijkt de belasting op suikerhoudende dranken ervoor te zorgen dat mensen minder frisdrank kopen en drinken. Het RIVM heeft in kaart gebracht hoe de suikertaks in het Verenigd Koninkrijk, Frankrijk en Noorwegen is vormgegeven. Vervolgens is bekeken wat de effecten van de belasting zijn op het aanbod, de samenstelling, de verkoop en consumptie van frisdrank, en op de mate waarin overgewicht voorkomt. Het doel van de belastingmaatregelen verschilt per land. Ook zijn het type belasting, de tarieven en de dranken die worden belast in elk land anders. Uit de beperkt beschikbare gegevens uit deze landen blijkt dat de verkoop van belaste frisdrank is afgenomen. In het Verenigd Koninkrijk en Noorwegen worden meer gezondere alternatieven verkocht. Het is alleen niet duidelijk in hoeverre deze veranderingen in de verkoop het directe gevolg zijn van de belasting. Er zijn aanwijzingen vanuit het Verenigd Koninkrijk dat de suikertaks ook de herformulering van frisdrank kan stimuleren. De suikertaks is een van de mogelijke maatregelen tegen overgewicht. Het is belangrijk consumenten een gezonder alternatief te bieden. Om te kunnen achterhalen of de suikertaks effectief is, moeten de effecten ervan op korte en lange termijn goed worden gemonitord.

Objective & Methods: The VALIGA study investigated the utility of the Oxford Classification of IgA nephropathy (IgAN) in 1147 patients from 13 European countries. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive treatments (CS/IS), and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present-central absent, local absent-central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results: All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy whilst the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity), and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. By contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes compared to central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion: We conclude that differences in the scoring of MEST-C criteria between local pathologists and central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

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Item does not contain fulltext Antiangiogenic therapy targeting vascular endothelial growth factor (VEGF) or its receptor (VEGFR) has proven its effect in the treatment of several types of cancer, including renal cell carcinoma (RCC). However, treatment can be accompanied by notable adverse effects. Mild proteinuria and hypertension are often seen, but sometimes nephrotic range proteinuria and/or renal insufficiency develop. In recent years insight into the toxic effects of anti-VEGF therapy in the kidney has increased. A few biopsies have been done and thrombotic microangiopathy is reported in the majority of cases. However, other patterns of kidney injury have been described as illustrated by the case of a 62-year-old patient who presented two years after initiation of the VEGFR inhibitor cediranib with a nephrotic syndrome and acute renal failure. Kidney biopsy disclosed focal segmental glomerulosclerosis (FS GS) and interstitial nephritis. Partial remission was achieved after stopping the cediranib and a short course of prednisone. We review the different forms of kidney injury that could be caused by anti-VEGF therapy. 01 augustus 2012

Item does not contain fulltext Focal segmental glomerulosclerosis (FSGS) is one the most important causes of the nephrotic syndrome in adult patients. FSGS is not a disease entity. The identification of underlying causes of FSGS (secondary FSGS) has increased our insight into the pathogenesis of FSGS. Moreover, differentiating between primary (idiopathic) and secondary forms of FSGS is important to allow appropriate treatment. Recently a new pathological classification of FSGS was proposed, expanding FSGS to include nonsclerotic lesions. In this review we discuss the current diagnostic and therapeutic options in patients with FSGS.

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

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Item does not contain fulltext Immunotactoid glomerulopathy (ITG ) is a rare cause of nephrotic syndrome, occurring in approximately 0.1% of native kidney biopsies. We describe a 43-year-old woman who presented with a nephrotic syndrome. Renal biopsy revealed a membranous pattern of glomerular injury. In electron microscopy the subepithelial deposits were comprised of 40 nm wide tubular structures, confirming ITG . During follow-up the patient developed a remission of proteinuria with only supportive treatment.

Routine chemical monitoring gives insight in the presence of contaminants in surface waters, but not in their joint ecological effects. Therefore ecological water quality is assessed with bioassays. Recently, a new bioassay using the chydorid Chydorus sphaericus has been developed. Working with smaller volumes, materials and being less time consuming than the traditional Daphnia magna test regarding the culture and experimental design, the 'Chydotox-test' shows a comparable sensitivity. The new Chydotox-test is a promising alternative for the existing Daphnia sp. acute immobilisation test (OECD 1984).

Item does not contain fulltext We present a patient with Morbus Wegener and crescentic glomerulonephritis. Treatment with cyclophosphamide and prednisolone resulted in the disappearance of signs and symptoms of systemic inflammation. However, renal function deteriorated. Renal biopsy showed evidence of continuing capillary necrosis. Renal function improved with added plasmapheresis treatment. This case report illustrates that in patients with vasculitis necrotizing glomerulonephritis may remain active despite immunosuppressive therapy, even in the absence of extrarenal disease activity.

Contains fulltext : 50733.pdf (Publisher’s version ) (Closed access) Glomerular diseases are caused by multiple mechanisms. Progressive glomerular injury is characterized by the development of segmental or global glomerulosclerosis independent of the nature of the underlying renal disease. Most studies on glomerular disease focus on the constituents of the filtration barrier (podocytes, glomerular basement membrane (GBM), endothelial cells) or the mesangial cells. Little attention is given to the epithelial cells lining Bowman's capsule, the so called parietal epithelial cells (PECs). This 'lack of attention' is partly explained by the presumed 'passive' function of PECs, which are large, flattened cells that cover Bowman's capsule in a single cell layer and form a barrier between the ultrafiltrate and the periglomerular interstitium, in normal glomerular physiology. A more important reason has been the lack of an established primary role for the parietal epithelium in glomerular diseases. However, in recent years, several studies have demonstrated that PECs are involved in extracapillary proliferation. In addition, PECs can become highly active, proliferating cells, expressing many growth factors, chemokines, cytokines, and their receptors. It was recently demonstrated that PECs also play a part in the development of focal segmental glomerulosclerosis (FSGS). This review summarises current knowledge of the PEC, with emphasis on the role of PECs in the development of FSGS.

Item does not contain fulltext We report a 62-year-old man with documented type 2 diabetes mellitus and hypertension, who presented with a rapid deterioration in renal function. The sudden decrease in renal function in this well-controlled diabetic patient prompted us to consider a nondiabetic and nonhypertensive cause. The urinary sediment showed a glomerular haematuria suggestive of glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary glomerulonephritis is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of renal function. A diagnosis of fibrillary glomerulonephritis can only be made by electronmicroscopy of the renal tissue. In this case report the spectrum of this disease is reviewed.

Contains fulltext : 47572.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently diagnosed idiopathic FSGS. METHODS: This was a retrospective study of patients with a diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria >3.5 g/day, normal renal function, duration of proteinuria or hypertension of less than one year, normal-sized kidneys, no underlying renal disease, and a negative family history. Renal biopsies were reviewed without knowledge of the clinical course. RESULTS: Twenty patients (13 male, 7 female) fulfilled the study criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/- 20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l. After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in remission of proteinuria. Renal function deterioration occurred in seven patients, and prompted treatment in four of them. The ten-year death-censored renal survival was 89%. Renal function deterioration and remission rate could be predicted by selectivity index, serum albumin at three months after renal biopsy and the percentage of glomeruli with segmental sclerosis. CONCLUSION: Focal glomerulosclerosis is not a single disease. Case definition using strict clinical criteria identifies a subgroup of patients with idiopathic FSGS who have a good prognosis. In the majority of these patients immunosuppressive therapy is not warranted.

Item does not contain fulltext BACKGROUND: The reported outcome of renal transplantation in patients with the hemolytic uremic syndrome (HUS) varies greatly, probably related to the diverse causes of HUS. In this single-center retrospective study, we have analyzed the recurrence rate, the incidence of acute rejections, and graft survival in patients suffering from adult-onset and childhood-onset HUS. METHODS: The medical records of 35 patients with end-stage renal disease caused by HUS, who received 50 renal allografts, were reviewed. A definite recurrence of HUS was diagnosed if both clinical and histologic signs of thrombotic microangiopathy (TMA) were present in the absence of any endovasculitis. If there were signs of mild endovasculitis, a probable recurrence was diagnosed. RESULTS: After first renal transplantation, 0 definite and 1 (6%) probable recurrence occurred in 18 patients with childhood-onset HUS, as opposed to 7 (41%) definite and 3 (18%) probable recurrences in 17 adult-onset HUS patients (odds ratio [OR], 13.4; 95% confidence interval [CI], 1.7-105.7). In the latter patients, early use of cyclosporine A increased the risk for recurrence. The incidence of acute rejections was increased compared with matched controls (OR, 1.52; 95% CI, 1.05-2.19 for adult-onset HUS and OR, 1.88; 95% CI, 1.34-2.62 for childhood-onset HUS). One-year graft survival in adult-onset HUS was poor (29%), whereas 1-year graft survival in childhood-onset HUS was comparable to matched controls. CONCLUSIONS: In adult-onset HUS, the recurrence rate and the incidence of acute rejections are high, resulting in a detrimental graft survival. In childhood-onset HUS, the recurrence rate is low, but the posttransplantation course is complicated by an increased incidence of acute rejections.

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Contains fulltext : 30916_focasegl.pdf (Publisher’s version ) (Open Access) Contains fulltext : 53542.pdf (Publisher’s version ) (Open Access) RU Radboud Universiteit Nijmegen, 29 november 2007 Promotor : Wetzels, J.F.M. Co-promotor : Steenbergen, E. 176 p.