Different Forms Of Glomerulonephritis Research Articles

Soluble Tumor Necrosis Factor Receptor 2: A Promising Predictive Biomarker for Renal Dysfunction in Membranous Glomerulonephritis.

Background and objective Membranous glomerulonephritis (MGN) is a common cause of adult nephrotic syndrome. Tumor necrosis factor-α (TNF-α)is a proinflammatory cytokine that signals by attaching to TNF receptors. TNF-α plays a pivotal role in the development and progression of different forms of glomerulonephritis. Several research findings suggest that TNF-α receptors (TNFR1 and TNFR2) arepredictors of estimated glomerular filtration rate(eGFR) decline. In light of this, this study aimed to explore the relationship between TNFR2 and eGFR, as well as the predictive role of TNFR2 in eGFR decline in MGN. Methods A total of 50 consecutive patients with a diagnosis of primary MGN based on renal biopsies and clinical workups were included in the study. TNFR2 levels in serum, urine, and gene expression were evaluated at baseline and after three months of follow-up by using enzyme-linked immunosorbent assay (ELISA) kits for TNFR2 (KTE60215, Abbkine, Wuhan, China). Cox regression was employed to determine the predictive significance of TNFR2 in persistent eGFR decline. Additionally, an ROC curve analysis was conducted to assess the prognostic value of TNFR2 in predicting persistent eGFR decline among MGN patients. Results Weassessed the levels of inflammatory markers TNF-α and TNFR2, examined their correlation with eGFR and renal injury, and investigated their potential in predicting persistenteGFR. Patients with MGN exhibited elevated levels of TNFR2 in their serum, urine, and gene expression compared to healthy individuals. Additionally, there was a positive correlation between serum TNFR2 and TNF-α, urine protein-creatinine ratio (UPCR), uric acid, and total cholesterol. Conversely, there was a negative correlation with eGFR, serum albumin, and calcium. Serum TNFR2 showed statistical significance in a univariate Cox regression analysis (HR: 1.010, 95% CI: 1.00-1.01, p = 0.045) for predicting a persistent decline in eGFR. However, it did not show significance concerning relapse and remission. An ROC curve was created to assess TNFR2's prognostic potential as a biomarker, demonstrating an AUC of 0.683, with a sensitivity of 68% and specificity of 64%. Conclusions Based on our findings, TNFR2 is a predictive biomarker for eGFR decline in MGN, correlating with renal inflammation and predicting deterioration in renal function. TNFR2 emerges as a promising biomarker for early identification in patients at risk of renal function decline.

Protocolo diagnóstico y tratamiento de la afectación renal en las enfermedades infecciosas

Infections may affect the kidneys through different mechanisms. The fundamental origin of lesions is often haemodynamic damage, as occurs in sepsis or diarrhoea caused by an infection. On other occasions the pathogen itself may cause a lesion directly in the renal parenchyma, as happens in some viral infections. Lastly, another common mechanism for involvement consists of an alteration in the immune response caused by an infection. Different forms of glomerulonephritis may be caused in this context. The purpose of this protocol is to specify in greater detail the diagnosis and treatment of the main forms of kidney involvement associated with infections.

POS-020 ARTIFICIAL INTELLIGENCE ASSISTED QUANTIFICATION OF COMPLEMENT CONVERTASES IN GLOMERULONEPHRITIS

POS-020 ARTIFICIAL INTELLIGENCE ASSISTED QUANTIFICATION OF COMPLEMENT CONVERTASES IN GLOMERULONEPHRITIS

Retinal drusen in glomerulonephritis with or without immune deposits suggest systemic complement activation in disease pathogenesis

Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational study compared drusen counts in different forms of glomerulonephritis. Consecutive individuals with glomerulonephritis attending a general renal or transplant clinic underwent retinal imaging with a non-mydriatic camera. Drusen were counted in deidentified images by trained graders, compared with matched hospital patients, and correlated with clinical features. Eighty-four individuals with glomerulonephritis had a mean drusen count of 10 ± 27 compared with 3 ± 8 in hospital controls (p = 0.007). Fourteen individuals with glomerulonephritis (17%) and 4 hospital controls (4/49, 8%) had increased drusen counts (≥ 10) (p = 0.20). Increased drusen counts ≥ 10 were present in 13 (13/63, 21%) of those with glomerulonephritis and immune deposits [membranous (n = 8), antiglomerular basement membrane nephritis (n = 6), FSGS (n = 49)], and one of the 21 (5%) with glomerulonephritis without immune deposits [ANCA-associated (n = 15), minimal change disease (n = 6)]. In antibody-mediated glomerulonephritis (n = 14), mean drusen counts were 2 ± 3 in individuals with normal kidney function, 16 ± 41 with impaired function and 5 ± 7 with kidney failure . Mean counts were 24 ± 56 in individuals with glomerular IgG deposits and 1 ± 1 in those without (p = 0.76), and 23 ± 60 with complement deposits and 4 ± 8 in those without. Drusen counts were also less in immunosuppressed individuals (p = 0.049). The demonstration of retinal drusen in some forms of glomerulonephritis is consistent with systemic complement activation, and suggests that treatment targeting the complement pathways is worthwhile.

MO235: TGF-Β1/PSMAD3 Dependent Signaling in Glomerulonephritis and Its Association With Renal Injury and Progression

Abstract BACKGROUND AND AIMS Transforming growth factor-β1 (TGF-β1) has long been considered as a potent, multifunctional cytokine that is involved in the pathogenesis of fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β1/Smad3 signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). METHOD We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3) and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression and their role in progression to CKD. RESULTS TGF-β1 expression correlated positively with segmental glomerulosclerosis (P = .025) and creatinine level at diagnosis (p = .002), while pSmad3 expression with interstitial inflammation (P = .024). In glomerulus, we recorded different expression patterns of pSmad3 in crescents, while concomitant expressions of strong Smad7 and moderate pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (P = .011), intense interstitial inflammation (P = .029) and lower serum complement 3 (P = .028) and complement 4 (P = .029). We also reported a significant preferable expression between pSmad3 and glomerular endothelial cells of proliferative GN (P = .045) and podocytes of non-proliferative GN (P = .005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (HR = 5.08; 95% CI 1.133–22.78; P = .034) was emerged as independent predictor for CKD. CONCLUSION TGF-β1/Smad3 dependent signaling is upregulated, especially in proliferative GN, with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.

Inferior vena cava thrombosis as a possible cause of nephrotic-range proteinuria: two case reports

BackgroundNephrotic-range proteinuria is a common reason for nephrological consultation in clinical practice. The differential diagnosis is wide, and generally focuses on different forms of glomerulonephritis, but other causes should not be overlooked, as illustrated in this article.Case presentationsWe report two female patients with nephrotic-range proteinuria. In the first case, a 46 year old Caucasian patient who suffered from extreme obesity (Body mass index (BMI) 77 kg/m2), acute kidney injury and nephrotic-range proteinuria were discovered during an emergency consultation for acute abdominal pain. The second patient (aged 52, also Caucasian) developed stage 4 chronic kidney disease and nephrotic proteinuria (protein/creatinine ratio 1821 g/mol) after accidental rupture of the inferior vena cava during a gastric bypass operation. On split-urine collection, both had a much higher degree of proteinuria during the day than during the night, compatible with orthostatic proteinuria. At further work-up, inferior vena cava thrombosis was diagnosed in both patients, whereas renal veins were patent.DiscussionAfter simple anticoagulation in the first case, and anticoagulation plus endovascular recanalization in the second, there was almost complete resolution of the orthostatic proteinuria and a strong improvement of the estimated glomerular filtration rate in both patients. These cases highlight that nephrotic-range proteinuria can be linked to inferior vena cava thrombosis, and that a split-urine collection may also be very useful in the diagnostic work-up of proteinuria in adults.

Nature and frequency of diagnosis of different forms of glomerulonephritis as cause of development and progression of chronic kidney disease in different regions of world, according to clinical and morphological studies with renal biopsy

Hypertensive disorders in pregnant women are a significant factor in the development of complications leading to maternal and perinatal mortality. However, most cases of adverse outcomes are preventable. The choice of drug therapy in this group of patients should be made on the basis of a complete analysis and risk stratification.Purpose of work.Consideration of modern classification, diagnostic methods and rational antihypertensive therapy of chronic arterial hypertension on the example of a clinical case of a pregnant patient in a therapeutic hospital.Case description. The presented work describes a case of severe arterial hypertension during the first trimester of pregnancy, poorly amenable to drug correction.Conclusion.The features of this clinical observation are the problems associated with the selection of antihypertensive therapy for severe arterial hypertension during low gestational age pregnancy, taking into account comorbidities

Transforming Growth Factor-β1/Smad Signaling in Glomerulonephritis and Its Association with Progression to Chronic Kidney Disease

Introduction: Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-β/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). Methods: We evaluated the immunohistochemical expression of TGF-β1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. Results: TGF-β1 expression correlated positively with segmental glomerulosclerosis (p= 0.025) and creatinine level at diagnosis (p = 0.002), while pSmad3 expression with interstitial inflammation (p = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p = 0.011), intense interstitial inflammation (p = 0.029), and lower serum complement (C) 3 (p = 0.028) and C4 (p = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p = 0.045) and in podocytes of nonproliferative GN (p = 0.005). Finally, on multivariate Cox-regression analysis, TGF-β1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168–31.627; p = 0.032) was emerged as independent predictor for CKD. Discussion/Conclusion: TGF-β1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-β1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation.

Гломерулярные поражения почек у детей с ювенильным ревматоидным артритом (обзор литературы)

Обзор литературы посвящен описанию различных форм гломерулонефрита (ГН) у детей с полиартикулярной и системной формами ювенильного ревматоидного артрита (ЮРА). В доступной литературе представлен 21 клинический случай развития ГН, а именно: ANCA-ассоциированный ГН, мезангиопролиферативный ГН, в том числе IgA- и IgМ-нефропатия, мембранозная нефропатия, фокально-сегментарный гломерулосклероз, болезнь минимальных изменений, экстракапиллярный ГН. Механизм гломерулярных поражений при ЮРА объясняется гиперпродукцией провоспалительных цитокинов, а также нефротоксическим действием базисных противовоспалительных лекарственных средств. Подробно проанализированы клинические проявления и эффективность проводимой терапии каждого варианта ГН у детей с ЮРА. Больше всего публикаций посвящено ANCA-ассоциированному ГН, который развился у пациентов с торпидным течением и высокой степенью активности полиартикулярной и системной форм ЮРА. Особенностью ANCA-ассоциированного ГН явилось наличие гиперкреатининемии и практически в половине случаев— развитие терминальной почечной недостаточности, несмотря на проводимую иммунодепрессивную терапию. Единичные случаи других вариантов ГН описаны более 10 лет назад. Клинически отмечались протеинурия и реже— нефротический синдром, что стало основанием для прижизненного морфологического исследования почек. Иммунодепрессивная терапия была эффективной при мезангиопролиферативном ГН и болезни минимальных изменений. Во всех случаях при фокально-сегментарном гломерулосклерозе, экстракапиллярном ГН отмечено формирование терминальной почечной недостаточности. Благоприятный прогноз оказался у детей с мембранозной нефропатией, индуцированной препаратами, после отмены последних. Представлены публикации с положительным терапевтическим эффектом применения генно-инженерных биологических препаратов при ANCA-ассоциированном ГН, IgМ-нефропатии, гормонорезистентном варианте болезни минимальных изменений у детей с ЮРА.

Nature and frequency of diagnosis of different forms of glomerulonephritis as cause of development and progression of chronic kidney disease in different world regions according to clinical and morphological studies with renal biopsy

The review presents current data on the prevalence of chronic glomerulonephritis in different regions of the world according to the data of in vivo studies of histology of renal biopsy specimens. The literature data on the significance of glomerulopathies in the development of chronic kidney disease and risk factors of its progression to the terminal stages are reflected. We analyzed data on the most common types of glomerulonephritis – IgA-nephropathy, lupus nephritis on the ratio of primary and secondary forms of glomerulonephritis, their significance in the development of arterial hypertension and cardiovascular complications of this pathology.

Renal Lesions of Juvenile Idiopathic Arthritis in Children: A Literature Review

The literature review presents current data on the frequency, mechanisms of development, clinical manifestations, diagnosis and treatment of renal AA-amyloidosis and describes different forms of glomerulonephritis (GN) in children with juvenile idiopathic arthritis (JIA). The frequency of AA renal amyloidosis in JIA in children ranges from 0.8% to 2%, in adults with JIA duration of 28.3 years - 8.9%. In recent years, against the background of immunobiological therapy, the incidence of AA-amyloidosis of the kidneys in adults has decreased to 2%. AA-amyloidosis of the kidneys most often develops in children with the systemic form, in adults - with systemic and polyarticular forms of JIA. The first symptom of AA-amyloidosis of the kidneys is isolated proteinuria, which transforms into nephrotic syndrome. The peculiarity of the nephrotic syndrome is the absence of hypercholesterolemia in most cases, combined in some patients with arterial hypertension, hematuria, and impaired renal function. The available literature presents clinical cases of renal GN in children with JIA, viz: ANCA-associated GN, mesangioproliferative GN, including IgA- and IgM-nephropathy, membranous nephropathy, focal-segmental glomerulosclerosis, minimal change disease, extracapillary GN. Most publications are devoted to ANCA-associated HN, which developed in patients with a torpid course and a high degree of activity of polyarticular and systemic forms of JIA. The peculiarity of ANCA-associated HN was the presence of hypercreatininemia and, in almost half of cases, the development of terminal renal failure, despite the ongoing immunosuppressive therapy. The main method confirming the diagnosis of AA-amyloidosis and renal HN is the intravital renal morphological study. The use of immunobiological drugs in renal AA-amyloidosis and HN in children with JIA has therapeutic efficacy.

Resistance index of the renal artery measured by doppler ultrasound as a predictor of graft function after kidney transplantation

Background/Aim. As an optimal treatment of choice for patients with the latest stage of chronic kidney failure (CKD), renal transplantation (Tx) is performed. The resistance index (RI) of the renal artery is measured by Doppler ultrasonography routinely at certain time intervals to show the condition of the renal graft. The value of RI > 0.75 is considered abnormal. The aim of the study was to determine the correlation between the values of the RI index and the function of the transplanted kidney. Methods. We analyzed retrospectively 63 patients in whom kidney transplant was done at the Clinic for Nephrology and Clinical Immunology, the University Clinical Center of Vojvodina, Novi Sad, Serbia, in the period from 2013 to 2017. Doppler of renal blood vessels was made to all examined patients in the first month after the renal trans-plantation. In addition to standard demographic data, all patients had the RI index and its relationship to the function of the transplanted kidney analyzed immediately after transplantation, as well as in the 6th, 12th, and 18th month, and in a certain number of patients in the 24th and 48th month after transplantation. Results. Out of 63 patients, 63.5% were men, and 26.5% were women, with an average age of 47.67 ? 13.62 years. The primary diseases in patients which led to the terminal CKD stage were hypertension in 33.3% and different forms of glomerulonephritis; while other diseases (diabetes mellitus, chronic pyelonephritis, eclampsia, polycystic kidneys, kidney agenesia, and unknown cause) were present in a lower percentage. RI < 0.75 was present in 73%, and RI > 0.75 in 27% of patients. There was no statistically significant association between RI and serum creatinine or creatinine clearance at a given time, and there was no connection between RI and gender, as well as length of previous treatment by HD. There was a statistically significant association between RI and age of kidney recipient, as well as Tx type. Conclusion. In the observed group of patients, RI of renal arteries did not prove to be a good predictor of the function of the transplanted kidney either in the early or later post-transplant periods. RI might have greater predictive significance if it were determined on or immediately after the transplantation procedure.

Incidence of glomerulonephritis in the western part of Switzerland over the last decade

Glomerulonephritis is a rare yet serious group of diseases with a high risk of progression to end-stage renal disease. For optimal healthcare planning, detailed epidemiological and demographic data are essential. Despite their clinical relevance, these data are largely lacking in Switzerland. The objective of this study was to assess the incidence of the different forms of glomerulonephritis in the western part of Switzerland and its changes over the last 10 years, compared with international data. We listed all renal biopsy reports analysed between 2007 and 2016 at the University hospital of Lausanne, the renal pathology reference centre of all hospitals in the cantons of Vaud, Fribourg, Valais and Neuchâtel. Biopsies with a first diagnosis of primary glomerulonephritis were included in the analysis. The incidence was calculated as the number of patients newly diagnosed with glomerulonephritis divided by the number of inhabitants of all the above-mentioned cantons during the year under review, as retrieved from the federal statistical office of Switzerland. We collected biopsy reports from 864 patients between 2007 and 2016; 168 biopsies met the inclusion criteria. The most common primary glomerulonephritis was IgA nephropathy at 32.7% of cases, followed by lupus nephritis (29.8%) and pauci-immune glomerulonephritis (11.9%). Overall, the mean incidence of glomerulonephritis was 1.3/100,000/year. Between 2007 and 2016, the incidence of all glomerulonephritis taken together remained stable. The same was true for the incidence of IgA nephropathy, lupus nephritis and pauci-immune glomerulonephritis. In contrast, we observed a trend towards higher creatinine levels, proteinuria and degree of interstitial fibrosis at diagnosis. The incidence of glomerulonephritis in the western part of Switzerland was low and remained stable over time, in line with European data.

Metabolic pathways and immunometabolism in rare kidney diseases

ObjectivesTo characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis.MethodsPatients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors...

The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study.

INTRODUCTION:Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).AIM:The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.MATERIAL AND METHODS:A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun” were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.RESULTS:Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed” rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.CONCLUSION:Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

Ablative Therapy in 2016 for Small Renal Masses

The survival rate of kidney graft after kidney transplantation has been improved following the introduction of current immune suppression drugs. However, the risk of recurrence or de novo glomerulonephritis still remains. Most forms of glomerular disease can recur after transplantation [1] but different forms of glomerulonephritis have widely different allograft outcomes. Whereas IgA nephritis recurs in up to one third of transplanted patients, this is not associated with adverse effects on graft survival. In contrast, recurrent focal segmental glomerulosclerosis (FSGS) has an unfavorable prognosis [2] and so early detection and appropriate treatment can be crucial. We are presenting here a patient with primary FSGS who developed acute kidney injury and heavy proteinuria in the first week post-transplant that responded completely to multiple plasmapheresis sessions and four doses of Rituximab.

Thyroid dysfunction and kidney disease: An update.

Thyroid hormones influence renal development, kidney hemodynamics, glomerular filtration rate and sodium and water homeostasis. Hypothyroidism and hyperthyroidism affect renal function by direct renal effects as well as systemic hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been associated with increased serum creatinine and decreased glomerular filtration rate. The reverse effects have been reported in thyrotoxicosis. Most of renal manifestations of thyroid dysfunction are reversible with treatment. Kidney disease may also cause thyroid dysfunction by several mechanisms. Nephrotic syndrome has been associated to changes in serum thyroid hormone concentrations. Different forms of glomerulonephritis and tubulointerstitial disease may be linked to thyroid derangements. A high prevalence of thyroid hormone alteration has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent in chronic kidney disease patients. Subclinical hypothyroidism and low triiodothyronine syndrome are common features in patients with chronic kidney disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal transplantation recipients, exhibit thyroid hormone alterations and thyroid disease with higher frequency than that found in the general population. Drugs used in the therapy of thyroid disease may lead to renal complications and, similarly, drugs used in kidney disorders may be associated to thyroid alterations. Lastly, low thyroid hormones, especially low triiodothyronine levels, in patients with chronic kidney disease have been related to a higher risk of cardiovascular disease and all-cause mortality. Interpretation of the interactions between thyroid and renal function is a challenge for clinicians involved in the treatment of patients with thyroid and kidney disease.

Independent or synergistic relationship of proteinuria and glomerular filtration rate on patient and renal survival in patients with glomerulonephritis?

Glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD) identifies patients at risk for death or end-stage renal disease (ESRD). CKD staging by GFR should incorporate proteinuria to augment risk stratification. We therefore tested the predictive power of the combination of GFR with proteinuria in patients with different histologically-diagnosed types of glomerulonephritis (GN). In a retrospective analysis, 2,687 patients with different forms of GN from 123 Austrian centres were investigated. Full data sets were available from 1,892 subjects. Classes of CKD on the basis of estimated GFR (eGFR) and of proteinuria grouped as <1, 1-3.5, and >3.5 g/24 h were tested for their association with all-cause mortality and ESRD. During a median follow-up of 130 months [interquartile range (IQR) 90; 178] 478 patients (25.3 %) died. Median eGFR was 49 ml/min/1.73 m(2) (IQR 24; 81) and proteinuria 3.8 g/24 h (IQR 1.7; 8.0). Adjusted multivariate Cox regression indicated that renal survival but not overall survival is related to proteinuria >3.5 g/24 h [as opposed to <1 g/24 h; hazard ratio (HR) 1.91] and shows progression to ESRD. However, subgroup analyses revealed that this risk with proteinuria >3.5 g/24 h exists only in patients with immunoglobulin (Ig)A GN (HR 4.93), miscellaneous GN (HR 1.74), and CKD stage 5 (HR 2.50). Additionally, proteinuria is a risk factor for renal survival in males more than in females with GN and proteinuria >3.5 g/24 h (HR 1.91). Proteinuria is a strong risk factor for renal survival particularly in patients with proteinuria >3.5 g/24 but not for all types of GN, nor for all CKD stages. Proteinuria is not a risk factor for overall survival in patients with GN.

Recurrence of glomerulonephritis after renal transplantation

Recurrence of glomerulonephritis following renal transplantation is considered an important cause of allograft failure. The incidence of recurrence of glomerulonephritis varies widely depending on the definition of recurrence (pathologic recurrence or clinicopathologic recurrence) and the original glomerular disease. Moreover the impact of recurrence of glomerular disease on allograft outcome varies widely between different forms of glomerulonephritis. Whereas IgA nephritis recurs in up to one third of transplanted patients, this is not associated with adverse effects on graft survival. In contrast, recurrent focal segmental glomerulosclerosis and membranoproliferative glomerulopathy have an unfavorable prognosis. Overall, long-term graft survival in patients transplanted for glomerulonephritis is comparable to survival in patients with other causes of ESRD. In recent years, several mechanisms for recurrent disease after transplantation (e.g. PLA2R antibodies in membranous nephropathy and suPAR in FSGS) have been identified, and these findings have helped to elucidate the pathogenesis of glomerular diseases. Although renal transplantation is the treatment of choice for end-stage renal disease as a consequence of glomerulonephritis, further studies are required to develop optimal strategies to prevent, diagnose and treat recurrent glomerular diseases.

Characterization and quantification of proliferating cell patterns in endocapillary proliferation

Endocapillary proliferation (EP) is a common pathological finding in proliferative glomerulonephritis (GN). Its appearance indicates the presence of active lesions of GN. In this study, we reinvestigated the pathological features of EP. Cell markers that included CD15, CD68, CD45RO, CD31 and alpha-smooth muscle actin (alpha-SMA) were used to identify the intraglomerular cells in renal biopsy tissues collected from patients with post-streptococcal acute GN (PSAGN), methicillin-resistant Staphylococcus aureus-associated GN (MRSAGN) with or without EP, membranoproliferative GN (MPGN) with or without EP, Henoch-Schönlein nephritis, immunoglobulin A nephropathy, membranous nephropathy and minimal change nephrotic syndrome. Proliferating cells and apoptotic cells were investigated simultaneously. The glomerular infiltrating polymorphonuclear leukocytes, macrophages, T cells, mesangial cells and endothelial cells were enumerated. In PSAGN, the glomerulus was enlarged and all cell types were greatly increased. In MRSAGN EP, the glomerulus was slightly enlarged with abundant infiltrating leukocytes and monocyte/macrophages and had moderate mesangial cell proliferation with negligible endothelial cell proliferation. In MPGN, the glomerulus markedly enlarged with multiple monocyte/macrophages and remarkable mesangial proliferation. The mesangial cells in EP glomeruli were highly activated as evidenced by alpha-SMA expression, particularly in PSAGN. This is the first report to use monoclonal antibodies specific for cell markers to quantitatively analyze and compare the proliferating cell types in EP glomeruli in different forms of GN. The results suggest that identification of the presence of polymorphonuclear leukocytes in the capillary lumen might help in differentiating between glomerular global and segmental EP.