Types Of Glomerulopathies Research Articles

Can a Single Glomerulus Morphology Implicate Successful Therapy?

Recurrent gross hematuria of glomerular origin is frequently encountered in clinical practice, and in absence of specific serological marker, renal biopsy is mandatory to address the definitive diagnosis, and set out an appropriate therapeutic protocol. Technical deficiencies associated with practice of renal biopsy are frequently encountered, as inadequate number of glomeruli or poor immunofluorescence staining of kidney biopsy specimen; however, these deficiencies can be offset by detailed electron microscopy analysis of a single abnormal glom.We present a single middle-aged Libyan woman, with a rare glomerular disease, related to abnormal activation of alternative complement pathway, where renal biopsy report was initially not adequate and lacking immunohistochemistry workup. However, electron microscopy reports a characteristic abnormal glomerular deposit, coupled with clinical and biochemical data that guided our therapeutic protocol.In a middle-aged female who presented with recurrent gross hematuria and nephrotic range proteinuria, we should suspect a glomerular pathology. Further to immunoglobulin A nephropathy or lupus nephritis, particularly in presence of complement abnormalities and negative serology for glomerulopathy-related autoantibodies, dense deposit disease and C3 glomerulonephritis that are rare complement mediated glomerulopathy should be considered as a seronegative lupus nephritis-equivalent, in terms of their membranoproliferative features on light microscopy, and when setting out appropriate therapeutic protocol. Patient and family counseling for C3 glomerulopathy is essential because this type of glomerulopathy has a recurrence rate after kidney transplant.

MO1018: Nephrotic Syndrome as a Paraneoplastic Entity

Abstract BACKGROUND AND AIMS Association between nephrotic syndrome (NS) and cancer is well known. However, it has been barely studied and sustained. Membranous nephropathy (MN) has often been identified as a glomerular paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year follow-up of MN is 10–20%. Incidence rates in other glomerulopathies are limited. Concomitant malignancy is associated with poor renal outcome in NS since therapy for cancer is a priority and immunosuppressive therapies for NS should be restricted. There is no consensus for cancer screening in patients with NS, with or without known risk factors for cancer. Our aim is to establish the incidence of neoplasia in a cohort of patients of two tertiary hospitals in Spain who develop NS. We analyze clinical characteristics, glomerular disease, types of malignancies and risk factors for cancer in this population. METHOD All patients > 18 years old with NS at one tertiary hospital in Madrid between January 2013 and December 2019 and at one tertiary hospital in Barcelona between January 2018 and June 2020 were included. Demographical and clinical data, laboratory results, and tests performed for cancer screening were recorded. Patients who presented cancer the year before or 24 months after the diagnosis of NS were identified. We performed a logistic regression model to identify independent risk factors for cancer in this population. RESULTS A total of 114 patients presented with NS during the study periods. A total of 57% were men, and the mean age was 57.28 ± 17.3 years. A total of 60% patients presented high blood pressure and 36% type 2 DM2; 7% patients presented HIV infection and 6% hepatitis C infection. A total of 44.7% reported smoking and 13.1% of alcohol consumption. More frequent histologic diagnosis were: diabetic nephropathy (17.5%), MN (14.9%), minimal change disease (7.9%) and membranoproliferative glomerulonephritis (7.9%). Eight patients presented positivity for anti-phospholipase A2 receptor antibodies. A total of 20 patients presented cancer (17.5%): 12 patients had a malignancy diagnosed the year before the NS onset (10 patients with solid organ malignancy and 2 patients with haematological cancer) and 8 patients 24 months after NS onset (3 patients with solid organ malignancy and 5 patients with haematological cancer). In the univariate analysis, patients with cancer were older (72.35 ± 10.28 versus 53.20 ± 17.13 years old; P < .0001). There were no differences in terms of smoking, viral infections, renal function, proteinuria or type of glomerulopathy. In a multivariate analysis, age was the only risk factor for cancer in patients with NS {OR = 1.122, [95% confidence interval (95% CI) 1.050–1.1980]; P = .0007}. Patients who were diagnosed with cancer were submitted more frequently to gastroscopy (50% versus 25.5%; P = .0323), colonoscopy (60% versus 26.6%; P = .038) and mammography (30% versus 11.7%; P = .370) as screening procedures for malignancy than those without cancer diagnosis. There were no differences in other screening procedures such as chest X-ray, fecal occult blood test, CT scan or abdominal ultrasound. CONCLUSION In our cohort, 17.5% patients with NS presented also concomitant cancer. Age was the only risk factor for neoplasia in this cohort. No association between cancer and gender, type of glomerulopathy, or known risk factors for neoplasia such as alcohol, tobacco or viral infection was found. Patients who were diagnosed with cancer were more frequently submitted to specific cancer screening procedures. It is important to develop screening strategies to find occult malignancy in patients with NS since this condition compromises renal outcome and life expectancy.

Immunotactoid glomerulopathy \u2013 an enigmatic case in the setting of nodal marginal zone lymphoma and systemic sclerosis sine scleroderma

BackgroundImmunotactoid Glomerulopathy (ITG) is an exceedingly rare type of glomerulopathy characterised by distinctive electron microscopic features. ITG has been linked to lymphoproliferative or autoimmune disorders. The clinical manifestations are diverse including nephrotic syndrome (NS), haematuria, acute kidney injury and end stage renal failure (ESRD). We present a case with a stage 3 Nodal Marginal Zone Lymphoma (NMZL) and systemic sclerosis sine scleroderma (SSSS), where the evolution of ITG was documented in 2 renal biopsies 19 months apart. To the best of our knowledge, no cases have been reported linking ITG to NMZL. Furthermore, there is only one non-peer reviewed report linking ITG to scleroderma. We discuss the implications of our findings and highlight the satisfactory management of the case.Case presentationA 79-year-old female with history of systemic sclerosis sine scleroderma and stage 3 NMZL presented with acute kidney injury and NS on a background of chronic kidney disease. Her first kidney biopsy showed a diffuse proliferative glomerulonephritis and her serum protein electrophoresis showed no abnormalities. She was managed satisfactorily with conservative measures. She returned 19 months later with features of fluid overload, increasing proteinuria and rising serum creatinine. A repeat serum protein electrophoresis showed excess free kappa light chains and ITG was detected in the repeat kidney biopsy. Her kidney function and proteinuria showed a good and sustained response to rituximab administered after the second biopsy.ConclusionITG is a rare type of glomerulopathy, associated with underlying haematological malignancies and autoimmune disorders that may result in ESRD.Rituximab is one of the effective agents used in the management of ITG with haematological malignancies.

Crescents in primary glomerulonephritis: a pattern of injury with dissimilar actors. A pathophysiologic perspective.

Cellular crescents are defined as two or more layers of proliferating cells in Bowman's space and are a hallmark of inflammatory active glomerulonephritis and a histologic marker of severe glomerular injury. In general, the percentage of glomeruli that exhibit crescents correlates with the severity of kidney failure and other clinical manifestations of nephritic syndrome. In general, a predominance of active crescents is associated with rapidly progressive glomerulonephritis and a poor outcome. The duration and potential reversibility of the underlying disease correspond with the relative predominance of cellular or fibrous components in the crescents, the initial location of the immunologic insult inside the glomerulus, and the sort of involved cells and inflammatory mediators. However, the presence of active crescents may not have the same degree of significance in the different types of glomerulopathies. The pathophysiology of parietal cell proliferation may have dissimilar origins, underscoring the fact that the resultant crescents are a non-specific morphological pattern of glomerular injury with different implications in clinical prognosis in the scope of glomerular diseases.

MO288NEPHROTIC SYNDROME AS A PARANEOPLASTIC ENTITY: ARE WE KEEPING IT IN MIND?

Abstract Background and Aims Association between nephrotic syndrome (NS) and cancer is well known. However, it has been barely studied and scarcely sustained. Membranous nephropathy (MN) has been identified often as a glomerular paraneoplastic disease. Reported incidence of cancer at the time of biopsy or one year follow-up of MN is 10-20%. Incidence rates in other glomerulopathies are limited. Concomitant malignancy is associated with poor renal outcome in NS. Therapy for cancer is priority and immunosuppressives therapies should be restricted. Furthermore, there is no consensus for cancer screening in patients with NS with or without known risk factors for cancer, as smoking or alcohol consumption. The aim of our study is to stablish the incidence of neoplasia in a cohort of patients of a tertiary hospital of Spain who develop NS. We analyze clinical characteristics, glomerular disease, type of malignancies, screening procedures and risk factors for cancer in this population. Method All patients with NS at our center between January 2013 and December 2019 were included. Demographical and clinical data, and laboratory results were collected, as well as all tests performed for cancer screening. Patients who presented cancer the year before or 24 months after the diagnosis of NS were identified. We performed a logistic regression model to identify independent risk factors for cancer in this population. Results During the study period, 47 patients presented with NS at our center. 38.3% were women and mean age was 57.28±17.3 years. 46.8% patients presented high blood pressure and 23.4% type 2 DM. 5 patients presented HIV infection, and 4 hepatitis C. 51% reported smoking, and 19% of alcohol consumption. Mean creatinine at NS diagnosis was 2.48±2.30 mg/dL, and proteinuria 10.9±6.7 g per day. Histologic diagnosis were: MN (n=7), membranoproliferative glomerulonephritis (n=5), diabetic nephropathy (n=5), and focal and segmental glomerulosclerosis (n=4). 9 out 47 patients presented cancer: 6 patients had a malignancy diagnosed the year before the NS onset (prostate carcinoma n=2, gastrointestinal carcinoma n=2, lung carcinoma n=1, and Hodgkin lymphoma n=1), and 3 patients one the year after the NS onset (thyroid carcinoma n=1, melanoma n=1, and multiple myeloma n=1). In the univariate analysis, patients with cancer were older (69.3±12.1 vs 54.4±17.2 years old, p=0.018) and had more frequently alcohol consumption (33.3% vs 15.8%, p=0.0187). There were no differences in terms of smoking, viral infections, renal function, proteinuria or type of glomerulopathy. In multivariate analysis including these two variables and gender, neither age nor alcohol intake were a risk factors for the presence of cancer in patients with NS. Conclusion: 19.1% patients with NS presented also concomitant cancer in our cohort, without association to the type of glomerulopathy, age or known risk factors for neoplasia such as alcohol, tobacco or viral infection. As our data showed, the presence of cancer in patients with NS is considerable, so the development of screening strategies to find occult malignancies in this group of patients is necessary since this condition compromises renal outcome and life expectancy

Type IV Collagen Mutations in Familial IgA Nephropathy

Type IV Collagen Mutations in Familial IgA Nephropathy

Glomerulosclerosis in transgenic rabbits with ubiquitous Venus protein expression.

Focal segmental glomerulosclerosis (FSGS) is a potential cause of nephrotic syndrome both in humans and pet mammals. Glomerulopathy was reported earlier in green fluorescent protein (GFP) transgenic (TG) mice, but glomerulosclerosis has not been examined in GFP TG rabbits so far. In the present study, the potential manifestation of FSGS was investigated in both Venus TG rabbits generated by Sleeping Beauty (SB) transposition and age-matched control New Zealand White (NZW) rabbits. Venus protein fluorescence was detected by confocal microscopy and quantified by microplate reader. Urinalysis, haematology, serum biochemistry and renal histology were performed to assess the signs of FSGS. Higher levels of Venus fluorescence were determined in renal cortex samples than in the myocardium by both methods. Urinalysis revealed proteinuria in Venus heterozygote TG bucks, while Venus homozygote TG bucks developed microscopic haematuria. Supporting the urinalysis data, the histological findings of FSGS (glomerulomegaly and sclerotic glomeruli) were observed in renal cortex sections of Venus TG rabbits. Taken together, Venus TG bucks were diagnosed with FSGS; thus, this type of glomerulopathy could be a common disease in TG animals overexpressing GFP.

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study

ObjectivesUrinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. MethodsAn exploratory study was performed; four groups of patients were analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3) patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and healthy patients (controls). ResultsIn all, 44 patients, with an average age of 35.9±11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE+LN compared with patients in the other groups: SLE+LN 12.88±8.33, SLE-LN 3.12±2.31, GMN 4.36±2.31 and controls 2.41±1.94pg/mg Cr (p=0.007). A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC) curve analysis revealed that uTWEAK levels above 4.91pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75–0.99). However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. ConclusionsOur study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy.

Assessment of urinary TWEAK levels in Mexican patients with untreated lupus nephritis: An exploratory study

ObjectivesUrinary levels of TWEAK (uTWEAK) may be correlated with the degree of lupus nephritis (LN) activity. Our objective was to determine the sensitivity and specificity of uTWEAK in Mexican patients with untreated active lupus nephritis. MethodsAn exploratory study was performed; four groups of patients were analyzed as follows: 1) patients with systemic lupus erythematosus (SLE) without renal activity (SLE-LN), 2) patients with SLE with renal activity (SLE+LN), 3) patients with other types of glomerulopathy (glomerulonephritis, GMN), 4) and healthy patients (controls). ResultsIn all, 44 patients, with an average age of 35.9±11.5 years, were evaluated. uTWEAK levels were higher in patients with SLE+LN compared with patients in the other groups: SLE+LN 12.88±8.33, SLE-LN 3.12±2.31, GMN 4.36±2.31 and controls 2.41±1.94pg/mg Cr (p=0.007). A total of 72.7% of the cases had renal activity index scores above 12, and 90.9% of the cases had scores of chronicity below 6 points. Receiver Operating Characteristic (ROC) curve analysis revealed that uTWEAK levels above 4.91pg/mg Cr had a sensitivity of 81% and a specificity of 75% for the diagnosis of renal activity due to lupus, with an area under the curve of 0.876 (95% CI: 0.75–0.99). However, no significant correlation was observed between the levels of uTWEAK and the histological findings specific to the activity and chronicity associated with SLE. ConclusionsOur study revealed that uTWEAK can adequately distinguish renal activity due to lupus, but cannot predict the degree of histological activity in Mexican patients with active lupus nephropathy.

The clinicopathologic characteristics of kidney diseases related to monotypic IgA deposits

Monoclonal gammopathy of renal significance (MGRS) regroups renal disorders caused by a monoclonal immunoglobulin without overt hematological malignancy. MGRS includes tubular disorders, glomerular disorders with organized deposits, and glomerular disorders with non-organized deposits, such as proliferative glomerulonephritis with monoclonal IgG deposits. Since glomerular involvement related to monotypic IgA deposits is poorly described we performed retrospective analysis and defined clinico-biological characteristics, renal pathology, and outcome in19 referred patients. This analysis allowed distinction between 2 types of glomerulopathies, α-heavy chain deposition disease (5 patients) and glomerulonephritis withmonotypic IgA deposits (14 patients) suggestive of IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits in 12 cases. Clinicopathologic characteristics of α-heavy chain deposition disease resemble those of the γ-heavy chain disease, except for a higher frequency of extra-capillary proliferation and extra-renal involvement. IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits should be differentiated from diseases with polytypic IgA deposits, given distinct clinical, histological, and pathophysiological features. Similarly to IgG-proliferative glomerulonephritis with monoclonal immunoglobulin deposits, overt hematological malignancy was infrequent, but sensitive serum and bone marrow studies revealed a subtle plasma cell proliferation in most patients with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Anti-myeloma agents appeared to favorably influence renal prognosis. Thus, potential progression towards symptomatic IgA multiple myeloma suggests that careful hematological follow-up is mandatory. This series expands the spectrum of renal disease in MGRS.

Clinical, laboratory, and morphological characteristics of kidney damage in lymphoproliferative disorders

Kidney involvement in the onset of lymphoproliferative diseases (LPD) detected rarely, observed mainly at tumor progression or relapse. Objective : to determine the clinical and morphological features of kidney damage in the initial manifestation of LPD. Materials and methods : 19 patients with LPD and kidney damage were included in the study. The diagnosis of non-Hodgkin’s lymphomas was established according to 2008 WHO classification. Histological and immunohistochemical, immunofluorescent and electron microscopic studies of nephrobiopsy have been performed. Results . Patients were aged 46-83 years (median 63 years), of which 13 were men and 6 women. Chronic lymphocytic leukemia / small cell lymphocytic lymphoma was established in 12 patients, marginal zone lymphoma – in 4 pts, follicular lymphoma – in 1 patient, Waldenstrom's macroglobulinemia – in 1 patient and diffuse large B-cell lymphoma (DLBCL) in 1 patient. Proteinuria was observed in 18 patients, microhematuria – in 6 pts, arterial hypertension – in 8 pts, nephrotic syndrome – in 3 pts and renal failure in 18 patients. The mean creatinine level was 330.9 ± 52.3 µmol/L, the average glomerular filtration rate was 25.7 ± 12.9 ml/min. Monoclonal IgMκ secretion was detected in 6 patients, BJκ protein – in 9 pts, increased free light chain level – in 4 pts, cryoglobulin – in 4 pts (type II cryoglobulin in 3 of them, type I – in 1 patient). Morphological study of nephrobiopsy revealed tumor lymphoid infiltration of kidney interstitium in 10 (52.6 %) cases. Diffuse small cell lymphoid proliferation was detected in 1 patient, local infiltration – in 9 pts, in 3 of them in combination with glomerulonephritis, and in 4 cases with kidney carcinoma. Local large cell lymphoid proliferation was found in 1 patient with DLBCL. Amyloidosis was detected in 2 pts and thrombotic microangiopathy – in 2 patients. Glomerulopathy was revealed in 10 patients (52.6 %): mesangioproliferative glomerulonephritis (MPGN) – in 4, mesangiocapillary glomerulonephritis – in 3, fibrillar glomerulonephritis (FGN) – in 1, immunotactoid glomerulonephritis – in 1, and glomerulonephritis with minimal changes – in 1 patient. Conclusion . Kidney damage in the onset of lymphatic tumor does not always manifest with proteinuria, hematuria, nephrotic syndrome and renal failure. In most cases, secretion of BJ protein, free light chains, monoclonal immunoglobulin and cryoglobulin are detected. Morphological changes are heterogeneous, including lymphoid proliferation, various types of glomerulopathies, amyloidosis and thrombotic microangiopathy.

Podocyte and Parietal Epithelial Cell Interactions in Health and Disease.

The glomerulus has 3 resident cells namely mesangial cells that produce the mesangial matrix, endothelial cells that line the glomerular capillaries, and podocytes that cover the outer surface of the glomerular basement membrane. Parietal epithelial cells (PrECs), which line the Bowman's capsule are not part of the glomerular tuft but may have an important role in the normal function of the glomerulus. A significant progress has been made in recent years regarding our understanding of the role and function of these cells in normal kidney and in kidneys with various types of glomerulopathy. In crescentic glomerulonephritis necrotizing injury of the glomerular tuft results in activation and leakage of fibrinogen which provides the trigger for excessive proliferation of PrECs giving rise to glomerular crescents. In cases of collapsing glomerulopathy, podocyte injury causes collapse of the glomerular capillaries and activation and proliferation of PrECs, which accumulate within the urinary space in the form of pseudocrescents. Many of the noninflammatory glomerular lesions such as focal segmental glomerulosclerosis and global glomerulosclerosis also result from podocyte injury which causes variable loss of podocytes. In these cases podocyte injury leads to activation of PrECs that extend on to the glomerular tuft where they cause segmental and/or global sclerosis by producing excess matrix, resulting in obliteration of the capillary lumina. In diabetic nephropathy, in addition to increased matrix production in the mesangium and glomerular basement membranes, increased loss of podocytes is an important determinant of long-term prognosis. Contrary to prior belief there is no convincing evidence for an active podocyte proliferation in any of the above mentioned glomerulopathies.

Quantitative Analysis of Four Types of Primary Glomeropathy by Application of a Decision Forest to Ultrasonic and Laboratory Characteristics

The aim of this study was to apply a decision forest to analysis of the ultrasound characteristics and laboratory test indices of four types of primary glomerulopathy, and quantitative analysis of the four pathologic types using a combination of these two methods. The decision trees were derived from 41 clinical indices and 5 characteristic sonographic indices obtained for the left kidney. Fifty-six patients who had undergone ultrasound-guided renal biopsy were reviewed retrospectively, and on pathologic examination, the patients were diagnosed with primary glomerulopathy, which includes mesangial proliferative glomerulonephritis, membranous nephropathy, immunoglobulin A nephropathy and minimal change disease. In this study, eight characteristic indicators were correlated with pathologic type in the 56 cases of primary glomerulopathy. The order calculated by decision forests, from high to low, is proteinuria, length of kidney, serum creatinine, plasma albumin, area of kidney, total protein, thickness of renal parenchyma, 24-h urine protein. The glomerulopathy with the highest ++++ proteinuria is membranous nephropathy, which accounts for 39.2% (22/56) of the total sample; this was followed by minimal change disease, mesangial proliferative glomerulonephritis and immunoglobulin A nephropathy. On the basis of our analysis of 41 clinical indices, the key indices for quantitative analysis of primary glomerulonephritis are laboratory tests, and these include urine protein, serum creatinine, plasma albumin, total serum protein and 24-h urine protein. The three key sonographic features are measurement indices: renal length, renal area and renal parenchymal thickness. From the eight characteristic indicators, we observed that with respect to severity (from most severe to least severe), the four types of glomerulopathy are membranous nephropathy, minimal change disease, mesangial proliferative glomerulonephritis and immunoglobulin A nephropathy.

Recurrent glomerular disease after kidney transplantation: an update of selected areas and the impact of protocol biopsy.

Recurrence of native kidney disease following kidney transplantation affects between 10% and 20% of patients, and accounts for up to 8% of graft failures. In a considerable number of recipients with transplant glomerulopathy, it is impossible to distinguish between recurrent and de novo types. An accurate estimate of the incidence of recurrence is difficult due to limitations in the diagnosis of recurrent glomerulonephritis. De novo glomerular lesions may be misclassified if histological confirmation of the patient's native kidney disease is lacking. Asymptomatic histological recurrence in renal allografts may be missed if protocol biopsies are not available. Studies based on protocol biopsy are pivotal to accurately estimate the incidence of recurrence. Many factors are known to influence recurrence of kidney disease after transplantation, including the type and severity of the original disease, age at onset, interval from onset to end-stage renal disease, and clinical course of the previous transplantation. Early recognition of recurrence is possible in several glomerular diseases. Factors such as the existence of circulating permeability factors, circulating urokinase receptor and anti-phospholipase A2 receptor antibody, as well as disorders of complement regulatory proteins like factor I mutation and factor H mutation factors are expected to be useful predictors of recurrence. Peculiar clinical course of atypical haemolytic uremic syndrome after kidney transplantation is an informative sign of recurrent glomerular disease. These factors play pivotal roles in the development of recurrence of certain types of glomerulopathies. Understanding the pathogenesis of recurrent glomerulonephritis is critical to optimize prevention as well as treat individual cases of recurrent glomerulonephritis. Subclinical recurrence of IgA nephropathy after kidney transplantation is well recognized. Only protocol biopsies of clinically silent recipient can provide the accurate prevalence of recurrent IgA nephropathy. The study of recurrent glomerulonephritis will contribute not only to improving long-term graft survival, but also to clarifying the pathogenesis of glomerulonephritis. Protocol biopsy is one the most effective methods for elucidating the pathogenesis of recurrent glomerulonephritis.

Diagnostic value of soluble urokinase-type plasminogen activator receptor serum levels in adults with idiopathic nephrotic syndrome

Recent studies suggest that soluble urokinase-type plasminogen activator receptor (suPAR) levels could be useful for distinguishing idiopathic focal segmental glomerulosclerosis (FSGS) from other glomerulopathies that cause nephrotic syndrome, but these data have not been confirmed in independent studies. The objective of our study is to analyse whether circulating levels of suPAR are useful for identifying primary kidney disease in patients with nephrotic syndrome secondary to FSGS, minimal change disease or idiopathic membranous nephropathy (MN). We measured circulating suPAR at diagnosis in 60 patients with nephrotic syndrome secondary to FSGS, minimal change disease (MCD) and membranous nephropathy (MN). The correlations between suPAR levels and demographic, clinical and biochemical variables were analysed. The sensitivity and specificity of suPAR in distinguishing FSGS patients were analysed by ROC curves. After adjusting for age and renal function, suPAR levels were significantly higher in patients with FSGS than in those with MCD (p<.001), but there were no differences between FSGS and MN (P=.12). A suPAR value ≥3452 pg/ml had a sensitivity of 73.7% and a specificity of 72.5%, with an area under the curve (AUC) of 0.782 ± 0.124, p=.001, for identifying patients with FSGS. After excluding patients with MN, a value ≥3531 pg/ml had a specificity of 99.93% for distinguishing between MCD and FSGS. suPAR values alone do not distinguish between the three types of glomerulopathy. Nevertheless, after excluding the diagnosis of MN, a suPAR level >3531 pg/ml could have a high specificity (but a low sensitivity) in the diagnosis of FSGS.

Atypical haemolytic uraemic syndrome with underlying glomerulopathies. A case series and a review of the literature

Primary or secondary glomerulonephritis has been anecdotally reported in association with atypical haemolytic uraemic syndrome (aHUS). We here report a series of six patients who developed aHUS and glomerulopathy, and review the literature on aHUS and glomerulonephritis. Out of all patients diagnosed at our unit with biopsy-proven glomerular diseases between March 2007 and October 2011, selected cases developing aHUS during the follow-up are presented. The following tests were performed in all six patients: serum C3 and C4 levels, ADAMTS13 activity, CFH levels and anti-CFH autoantibodies and genetic screening for CFH, MCP, CFI, C3 and CFHR1-3 mutations and risk haplotypes associated with aHUS. Two hundred and forty-eight patients received a biopsy-proven diagnosis of glomerulopathy and were followed for a median of 31 months (range 2-58). Of these, six developed aHUS, within a median of 15 months (range 1-36) of their initial diagnosis of glomerulopathy. One of these patients had focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN) type I, one C3 glomerulonephritis and two systemic small vessel vasculitis [one granulomatosis with polyangiitis (Wegener's), one Henoch-Schoenlein purpura]. Five patients (one of them heterozygous for a CFH mutation) carried, in homo- or heterozygosity, the risk haplotype CFH-H3 (CFH tgtgt), previously described to be associated with aHUS, while another one patient was homozygous for the MCPggaac risk haplotype predisposing to aHUS when present on both alleles. Different types of glomerulopathies can be complicated by aHUS. Several mechanisms can contribute to this association, such as nephrotic-range proteinuria, mutations or aHUS-risk haplotypes involving genes encoding alternative complement regulatory proteins in some patients and inflammatory triggers associated with systemic immune-mediated diseases.

Renal involvement in idiopathic hypereosinophic syndrome.

The hypereosinophilic syndromes (HESs) are a group of disorders marked by the sustained overproduction of eosinophils, in which eosinophilic infiltration and mediator release cause damage to multiple organs. In idiopathic HES, the underlying cause of hypereosinophilia (HE) remains unknown despite thorough aetiological work-up. Kidney disease is thought to be rare in HES. Renal manifestations described include eosinophilic interstitial nephritis, various types of glomerulopathies, thrombotic microangiopathy (TMA) and electrolyte disturbances. The diagnosis must be made in time, because a recovery of renal function can be obtained if treatment is initiated promptly.

THE ROLE OF PARICALCITOL ON PROTEINURIA

Paricalcitol is a synthetic vitamin D analogue acting on vitamin D receptor (VDR). The result is inhibition of PTH synthesis and secretion. Paricalcitol appears also to block the renin-angiotensin-aldosterone system. We evaluated the role of paricalcitol in the management of proteinuria of various aetiology. A total of 19 patients participated. Most had diabetic nephropathy; however patients with other types of glomerulopathy leading to proteinuria were also included. Paricalcitol 1-2 μg daily, according to response, was administered for three months. Serum Ca, PO4, Ca × PO4, PTH, creatinine clearance and albumin, as well as 24 hour urine protein were measured before and after treatment. Five out of 19 patients did not respond to the treatment. The remaining 14 patients had an average 32.9% reduction of proteinuria. The drug was well tolerated. Paricalcitol appears to have a role in the treatment of proteinuria. However, our study raises a question regarding why some patients do not respond to paricalcitol. Patients with proteinuria due to diabetic nephropathy seem to respond better than patients with glomerulopathy.

Genetical, histological, and clinical characteristics of IgA-negative mesangioproliferative glomerulopathy

Mesangioproliferative glomerulopathy (MesPGN) is a well-defined pathohistological entity. However, the clinical characteristics and prognosis have not been fully established in patients without immunoglobulin (Ig)A (N-IgAN) in contrast to patients with IgA nephropathy (IgAN). A total of 837 consecutive patients underwent renal biopsies. Among them, 465 patients were diagnosed with MesPGN by light microscopy. With immunofluorescent study and electron microscopy (EM), 344 were diagnosed as having IgAN. Among the rest, 84 patients who had no immunofluorescence evidence of IgA and no deposits in EM were defined as N-IgAN. We compared the clinical characteristics, histological findings, and genotypes of the angiotensin-converting enzyme (ACE) gene and plasminogen activator inhibitor-1 gene between IgAN and N-IgAN patients. Urinary protein excretion and the degree of hematuria were significantly lower in N-IgAN than IgAN patients (0.50 vs. 0.82 g/day; P = 0.01), (1.33 vs. 2.50; P < 0.001, respectively). Creatinine clearance was higher in N-IgAN than IgAN patients (89.4 vs. 74.4 ml/min; P < 0.001). Histopathologically, N-IgAN patients had significantly less advanced glomerular and tubulointerstitial lesions than IgAN patients. Pathological grades in patients with untreated IgAN were more advanced in a time-dependent manner, whereas there was no relationship between histological grades and time of illness in N-IgAN patients. Frequency of the DD genotype of the ACE gene was significantly lower in N-IgAN (DD/ID+II = 8/76) than IgAN (24/90) patients. IgA-negative MesPGN is a distinct type of glomerulopathy with a benign renal prognosis. Insertion/deletion polymorphisms of the ACE gene may play some role in the genesis and progression of MesPGN.

Thyroid dysfunction and kidney disease

Thyroid hormones (TH) are essential for an adequate growth and development of the kidney. Conversely, the kidney is not only an organ for metabolism and elimination of TH, but also a target organ of some of the iodothyronines' actions. Thyroid dysfunction causes remarkable changes in glomerular and tubular functions and electrolyte and water homeostasis. Hypothyroidism is accompanied by a decrease in glomerular filtration, hyponatremia, and an alteration of the ability for water excretion. Excessive levels of TH generate an increase in glomerular filtration rate and renal plasma flow. Renal disease, in turn, leads to significant changes in thyroid function. The association of different types of glomerulopathies with both hyper- and hypofunction of the thyroid has been reported. Less frequently, tubulointerstitial disease has been associated with functional thyroid disorders. Nephrotic syndrome is accompanied by changes in the concentrations of TH due primarily to loss of protein in the urine. Acute kidney injury and chronic kidney disease are accompanied by notable effects on the hypothalamus-pituitary-thyroid axis. The secretion of pituitary thyrotropin (TSH) is impaired in uremia. Contrary to other non-thyroidal chronic disease, in uraemic patients it is not unusual to observe the sick euthyroid syndrome with low serum triodothyronine (T(3)) without elevation of reverse T(3) (rT(3)). Some authors have reported associations between thyroid cancer and kidney tumors and each of these organs can develop metastases into the other. Finally, data from recent research suggest that TH, especially T(3), can be considered as a marker for survival in patients with kidney disease.