Proteinuria selectivity index based upon α2-macroglobulin or IgM is superior to the IgG based index in differentiating glomerular diseases: Technical Note

Diagnostic and prognostic significance of proteinuria selectivity index in glomerular diseases

The proteinuria selectivity index (SI) is a valuable marker of glomerular permeability. Traditionally, SI has been calculated using the clearance ratio of immunoglobulin G (IgG) to transferrin-SI (Tf)-due to historical limitations in albumin measurement accuracy. However, recent advances have enabled precise quantification of albumin, raising the possibility of using an albumin-based SI-SI (Alb)-in clinical practice. This study aimed to evaluate the correlation between SI (Alb) and SI (Tf) and to compare their diagnostic utility in patients with proteinuria. We retrospectively analyzed 265 patients with proteinuria > 0.15g/g·Cr who visited Ehime University Hospital between January 2014 and April 2024. SI (Alb) and SI (Tf) were calculated as the clearance ratios of IgG to albumin and IgG to transferrin, respectively. Linear regression was used to assess their correlation. Diagnostic performance for minimal change disease (MCD) in patients with nephrotic-range proteinuria (≥ 3.5g/g·Cr) was evaluated using ROC curves, and AUCs were compared using DeLong's test. SI (Alb) strongly correlated with SI (Tf) in patients with proteinuria ≥ 3.5 and < 3.5g/g·Cr. Among patients with nephrotic-range proteinuria, both indices effectively identified MCD, yielding comparable areas under the ROC curve. Sensitivity and specificity at optimal thresholds were similarly high. SI (Alb) shows a high degree of concordance with SI (Tf) and offers comparable diagnostic accuracy for identifying MCD. Given its practical advantages, SI (Alb) may serve as a reliable and convenient alternative to SI (Tf) for assessing glomerular selectivity in patients with proteinuria.

Urinary CD 80 in Nephrotic Syndrome: A Biomarker to Distinguish Minimal Change Disease From Other Glomerular Diseases

AIM: To investigate vascular endothelial growth factor (VEGF) mRNA expression in glomerular disease in the context of heavy proteinuria. METHODS: Non-radioisotopic in situ hybridisation was performed using a cocktail of...

De Novo and Relapsing Glomerular Diseases After COVID-19 Vaccination: What Do We Know So Far?

Minimal Change Disease: More Than a Podocytopathy?

Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases

In order to predict the steroid response in lipoid nephrosis (LN), we studied age, sex, proteinuria level, histological features and proteinuria selectivity index (SI; ratio between IgG and transferrin clearances) in 52 LN cases (minimal-change disease: n = 39; focal glomerulosclerosis+IgM nephropathy: n = 13). The multivariate analysis showed that age, sex and proteinuria level were not contributive, whereas histology and SI were. The predictive value of SI was much higher than that of histological type (McFadden's r2: 47% vs. 22%, p < 0.001). Thus, SI should be systemically assessed in idiopathic nephrotic syndrome for reviewing the pathologic classification obtained by histology. However, if its prognostic value is lower than that of selectivity, initial renal biopsy remains necessary for diagnosis in adults.

Quiz Page November 2013: An Unusual Cause of Nephrotic Syndrome

alpha 2-macroglobulin (alpha 2M) is a glycoprotein involved in delivery of growth factors, regulation of matrix degrading enzymes and modulation of fibrinolysis factors, all of which are considered as important pathogenic mechanisms of glomerular injury. However, the role of alpha 2M in glomerular disease has not been extensively studied. The amount, frequency and local distribution of alpha 2M in diseased glomeruli are similarly undetermined. Two hundred and fifty renal biopsy cases with glomerular disease were collected. The glomerular deposition of alpha 2M was surveyed with immunofluorescence-microscopy and intraglomerular localization of alpha 2M was assessed by immunoelectron-microscopy. To clarify the relationship between circulatory concentration and local deposition of alpha 2M, serum samples were collected at time of biopsy and alpha 2M was determined using radial immunodiffusion assay. The amount and frequency of local deposition of alpha 2M in glomeruli varied from disease to disease, and the average positive rate was approximately 20%. Patients with minimal-change nephrotic syndrome and IgM nephropathy not only had the highest mean serum alpha 2M concentration but also exhibited higher frequency of glomerular deposition of alpha 2M (25.9 and 30% respectively). The local deposition of alpha 2M revealed by optical and electron-microscopy may not be directly related to the high serum level of alpha 2M. The deposited alpha 2M was observed to associate with electron-dense deposits, mesangial matrix and mesangial cells. To our knowledge, this is the first report that reveals the ultrastructural distribution of alpha 2M in glomerular disease. The relatively selective deposition of alpha 2M in some glomerular diseases strongly indicates that alpha 2M may play an active role in the modulation of local inflammatory reaction and tissue repair in these glomerular diseases.

Background: The histological pattern and frequency of glomerular diseases differs according to the geographic area, race, age and indications for renal biopsy. This study was conducted to evaluate the frequency of different histological patterns of glomerulonephritis during a 10 years period at our institute. Study Design: Retrospective Case series. Period: 1st January 2007 to 31st, December 2017. Study Setting: Institute of kidney diseases, Hayatabad Medical Complex Peshawar, Pakistan. Results and Discussion: Clinical records of 415 native renal biopsies performed in patients with mean age 27.17 ± 14.98 years were included in this study. Males were 266 (64.1%) and females 149 (35.9%). Data was analysed for three age groups separately, Children (&lt;18 years) 147 (35.5%), Adults (18-59 years) 253 (61.0%) and elderly (&gt;60 years) 15 (3.6%). Primary GN (glomerulonephritis) was the most common (74.21%) followed by secondary GN (26.41%). Among primary glomerular diseases, Focal segmental glomerulonephritis (FSGS) was (29.6%), membranoproliferative glomerulonephritis (MPGN) also known as mesangiocapillary glomerulonephritis constituted 19.5% and Membranous glomerulonephritis (MGN) was the third most common (16.6%). Among secondary GN, acute tubular necrosis (ATN) was the most common (25.4%), followed by amyloidosis (14.7%), hypertensive nephropathy (13.7%) and lupus nephritis (12.8%) respectively. There was a slight male predominance in all types of primary GN except for focal necrotizing GN and most of the secondary types except lupus nephritis and chronic tubulointerstitial nephritis (TIN). Below 18 years, MPGN was (58.3%), focal necrotising GN (57.1%) and minimal change disease (MCD) was (52.2%). Crescentic GN (89.5%), MGN (74.5%), immunoglobulin A (IgA) nephropathy (72.7%), chronic sclerosing GN (CSGN) (64.7%) and FSGS (56%) were more common in adults. Frequency of immunoglobulin M (IgM) nephropathy (50%) was equal in children and adults. In elderly patients, the commonest GN reported was hypertensive nephropathy (28.6%), amyloidosis (6.7%) and MGN (5.9%). Conclusion: Among the wide variety of histological patterns, FSGS was the commonest GN in adults followed by MPGN and MGN. Among adults, primary GN was more common. When compared with other studies, FSGS is more common in the present study and some Indian studies, while membranous GN is more common in other regional countries.

Introduction: Although several registries collecting data of patients with kidney diseases exist, only a few specifically collect data relating to renal biopsy. Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this study was to report the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on histological diagnoses during the years 1977 through 2005. During this time, 3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446) and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies were not diagnostic, so in this paper we report data regarding 3,269 native kidney nephropathies. Methods: During the years 1977 through 2005, data for renal biopsies were collected on specific registers filled out by clinicians. Information collected in the database included a variety of indicators, such as clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels, blood pressure, height and weight, clinical presentation, and current medications. Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were divided into 4 major categories: primary glomerulonephritis (GN), secondary GN, tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN). Results: From 1977 up to 1987, a mean of 95 ± 18 renal biopsies/year were performed; this number significantly increased to 185 ± 22 renal biopsies/year (range 138-200) (p&amp;lt;0.001) in the following period (1988-2005). Renal biopsy was more frequently performed in males (59%) compared with females (41%). Of all diseases of the native kidney, primary GN was the most frequent (66%), followed by secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age, renal biopsy was more frequently performed in patients aged 20 to 60 years, and nearly 60% of patients presented a glomerular filtration rate (GFR) &amp;gt;60 ml/min at the time of biopsy. The main clinical reason for performing renal biopsy was UA, in all the types of nephropathies. Conclusions: We confirm data that renal diseases are more frequent in men, with the exception of secondary GN. The mean age at diagnosis was 42 years resulting from the tendency not to perform renal biopsies in children and in elderly patients. Renal biopsy was mainly performed in patients with GFR &amp;gt;60 ml/min and asymptomatic urinary abnormalities suggesting concern on the part of clinicians regarding glomerular diseases. The tendency to perform renal biopsies has been significantly increasing throughout our follow-up period.

The challenge in diagnosing de novo minimal change disease after transplantation.

Studies published from centers across India have reported different and contradicting patterns of glomerular disease. In this retrospective study, we report our experience from a Tertiary Care Center in Northwest India. A total of 702 renal biopsies performed between 2008 and 2013 were reviewed of which 80 were excluded from the study because of having insufficient records or if the biopsies were taken from an allograft. The study included 411 males (66.1 %) and 211 females (33.9%) with an age range of 12-70 years (mean 30.34 ± 7.04 years). Majority of the biopsies (93.9%) showed some form of glomerulonephritis (GN), either primary (79.4%) or secondary glomerular disease (SGD) (14.5%). Minimal change disease (MCD) was the most common type of primary GN (26.5% of primary GN), followed by membranous nephropathy (MN; 18.8%) and focal and segmental glomerulosclerosis (FSGS; 13.2%). Lupus nephritis (LN) was the most frequent SGD (52.2% of secondary GN). Amyloidosis was found in 41.1% and diabetic glomerulosclerosis in 4.4%. LN was also the second most common diagnosis in females after MCD, seen in 19.4% of females. MCD followed by membranoproliferative GN and diffuse proliferative GN were the most common entities in individuals <20 years of age. In the 20-39 years age group, MN was the most common pathology seen. MN was again the most common pathology seen in patients aged above 40 years followed by amyloidosis and FSGS. In this study, MCD was the most common primary GN observed overall from this part of India. MN was the most common GN in individuals above 20 years of age presenting with the nephrotic syndrome. The geographical and regional differences in the pattern of GNs point to the necessity of having a central biopsy registry.

Renal biopsy is the definitive diagnostic test in patients with renal parenchymal disease. Renal biopsy registry is an important tool which can provide valuable data concerning early and correct epidemiological description and clinical correlations of renal diseases. Records of 326 adult renal biopsies performed at our hospital from January 1991 till the end of December 2006 were retrospectively examined.Overall, secondary glomerular diseases (SGD) were predominant (39.9%), followed by primary glomerular diseases (PGD) (30.4%), vascular diseases (13.2%) and TIN (6.7%). Total sclerosis of the kidney did not allow histopathological diagnosis in 5.8% of all biopsied kidneys. Focal and Segmental Glomerular Sclerosis (FSGS), IgA Nephropathy (IgAGN) and Minimal Change Disease (MCD) and Membranous Glomerulopathy (MGN) were the most common PGD, altogether representing 75.7% of all PGD. FSGS was the most frequent (30.3%), followed by IgAGN (21.2%), MCD (19.1%) and MGN in 15.1%.Vasculitis, HIVAN, diabetic nephropathy and amyloidosis were the most common SGD, altogether representing 90% of all SGD. Immune Mediated Glomerulonephritis (IMGN) were the most frequent (32.3%), followed by HIVAN (16.9%), diabetic nephropathy (14.6%) and amyloidosis (10%). Nephroangiosclerosis (benign and malignant nephroangiosclerosis) was the most frequent vascular nephropathy responsible for 79% of all vascular diseases. Thrombotic microangiopathy was seen in 9.3% and atherothrombotic disease in 7% of all vascular diseases.Concerning tubular diseases, chronic TIN accounted for 63.6% of all tubular diseases, followed by light chaincast nephropathy (22.7%) and acute TIN (13.6%). Becauseof lack of material, 3.4% of all biopsies could not be analyzed. These data demonstrate that the distribution of biopsy-proved renal diseases in a Belgian population of the Brussels area is strongly influenced by the indications of renal biopsy. Harmonization of these indications might reflect with more accuracy the actual incidence of different nephropathies in a given population.Nation and worldwide renal biopsy registers are important to follow patterns of renal diseases in different populations. This information is important not only for health organizations in order to plan health budget but also for helping clinicians to provide a better care to patients.