Segmental Glomerular Sclerosis Research Articles

Anti-nephrin autoantibodies: novel predictors of post-transplant recurrence of focal segmental glomerular sclerosis

Anti-nephrin autoantibodies: novel predictors of post-transplant recurrence of focal segmental glomerular sclerosis

Clinical analysis of sirolimus therapy in children with refractory nephrotic syndrome

To investigate the clinical efficacy of sirolimus in treating children with refractory nephrotic syndrome, the clinical data for 22 children from the Children's Hospital of Hebei Province were analyzed retrospectively. There were 16 boys and six girls, and the treatment period was from September 2015 to April 2021. There were two patients with steroid-dependent nephrotic syndrome (SDNS), six patients with frequently relapsing nephrotic syndrome (FRNS), and 14 patients with steroid-resistant nephrotic syndrome (SRNS). All patients were defined as having refractory nephrotic syndrome. There were 12 patients (including nine SRNS patients and three FRNS patients) with minimal change disease (MCD), three patients (three SRNS patients) with focal segmental glomerular sclerosis (FSGS), one FRNS patient with mesangial proliferative glomerulonephritis (MsPGN), and six patients without a kidney biopsy. Compared with levels before sirolimus treatment, 24-hour urine protein (24-h UP), low-density lipoprotein cholesterol (LDL-C), urea (Ur) and serum creatinine (SCr) levels were significantly lower (all p < 0.05). Moreover, albumin (Alb) was significantly increased (p < 0.05), and there were no significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), immunoglobulin A (IgA), immunoglobulin G (IgG) or immunoglobulin M (IgM) (all p > 0.05) at the first follow-up. Sirolimus is effective as the first treatment of some children with refractory nephrotic syndrome, but its long-term efficacy and adverse reactions still require follow-up.

Tubulointerstitial nephropathy is the predominant finding in men in a review of more than 3000 renal biopsies over a 10-year period from Sri Lanka

BackgroundChronic kidney disease (CKD) is a significant clinical challenge in Sri Lanka. The present study presents histopathological diagnoses from native renal biopsies in Kandy District, 2011–2020.MethodsReports of 5,014 renal biopsies principally performed at Kandy Teaching Hospital over 2011–2020 were reviewed. After exclusions for post-kidney transplant biopsies (1,572) and those without evident pathology (347), 3,095 biopsies were included. The predominant histopathological entities were grouped and categorised according to diagnosis and stratified by age and sex.ResultsThe main histopathological entities (all biopsies) were tubulointerstitial nephropathy (TIN) 25% (n = 760), glomerulonephritis (GN) 15% (467), lupus nephropathy 14% (429), focal segmental glomerular sclerosis (FSGS) 10% (297), and IgA nephropathy (IgAN) 8% (242). For adult women ≥ 15 years, the main histopathological entities were lupus nephropathy 24% (325), TIN 17% (228), and GN 16% (217). For adult men ≥ 15 years, the main histopathological entities were TIN 34% (449), GN 14% (180), and IgAN 10% (125). The proportion of TIN in the present study was higher than international studies of a similar size.ConclusionThis is the largest study of renal biopsies reported from Sri Lanka to date. TIN was the most common diagnosis in adults ≥ 15 years at 25%. Notable sex differences showed TIN was the most common histopathology in men (34%) but not in women (17%). No previously published similar study of this size has found TIN as the predominant diagnosis amongst renal biopsies in men. Further research is required into the possible causes of these observations in Sri Lanka.Clinical Trial Number.Not applicable.

Postpartum Renal Cortical Necrosis: A Case Series

Rationale & ObjectivePostpartum renal cortical necrosis (postpartum RCN) is a severe form of obstetric acute kidney injury. This study aimed to identify clinicopathological features in Chinese postpartum RCN cases to determine how pathologic findings may contribute to the treatment and prognosis. Study DesignSingle-center, case series Setting & ParticipantsTwelve patients with postpartum RCN had kidney biopsies at Peking University First Hospital between 2014 and 2021. The diagnosis of postpartum RCN was made according to typical MRI or pathological features. Clinical, laboratory and pathological data were compared between patients with eGFR <30 (poor outcome) and ≥30 ml/min/1.73 m2 after six months. ObservationsAll postpartum RCN patients presented with stage 3 AKI attributed to a probable atypical hemolytic uremic syndrome. Pregnancy terminations occurred at a median gestational age of 35.5 weeks. Kidney biopsy was performed ranging 18 days to 4 months from delivery. Upon biopsy, hemoglobin, platelet count and LDH levels had been restored to 137 g/L, 214 ×109/L and 231.50±65.01 U/L, respectively. Four patients exhibited poor outcome, demonstrating higher schistocyte count, serum creatinine and mean arterial pressure at onset. Pathologically, glomerular segmental sclerosis was prevalent. The NOS variant was the most common type, followed by collapsing variant, cellular variant, and tip variant. Patients with poor kidney outcome had more glomerular coagulative necrosis, capillary thrombosis, extensive cortical coagulative necrosis, and pronounced arteriole/artery lesions including increased interlobular arteriole intimal edema and fibrin thrombosis, but a lower occurrence of segmental sclerosis. LimitationsLimited sample size and retrospective design. ConclusionsOur research has identified key pathological features in postpartum RCN patients with aHUS, highlighting the necessity for more effective therapeutic options. There is a clear demand for non-invasive biomarkers that can accurately track disease progression and inform treatment duration for long-term outcomes improvement.

Immunosuppressant-resistant nephrotic syndrome and primary amenorrhea: A case report of adult Frasier syndrome and literature review.

We present a case of a 19-year-old who developed nephrotic syndrome with preserved renal function. Renal biopsy confirmed focal segmental glomerular sclerosis (FSGS). No remission was achieved despite 2 years of treatment with glucocorticoids, mycophenolate mofetil, tacrolimus, and cyclophosphamide. After transfer to our center, we performed re-examination of renal pathology by electron microscope (EM), chromosomal karyotype, and gene analysis. EM revealed uneven thickness of the glomerular basement membrane without obvious stratification or fracture. Gene analysis revealed a splice mutation (1447+1G>A) in IVS9 and chromosomal karyotype was (46, XY), confirming the diagnosis of Frasier syndrome, which was consistent with primary amenorrhea overlooked by local nephrologists. Cyclosporin A was prescribed to reduce the proteinuria, but serum creatinine increased to 152 μmol/L.

Differentiated metabolomic profiling reveals plasma amino acid signatures for primary glomerular disease

Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography–tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD.

Astragaloside IV Protects Against Podocyte Injury by Upregulating Mitophagy via the Mfn2/Pink1/Parkin Axis.

Podocyte injury is the most important pathological hallmark of kidney diseases. Autophagy is a critical factor that involves podocyte injury. Here, we sought to determine whether Astragaloside IV (AS-IV) was able to improve renal function and reverse podocyte injury through the regulation of autophagy. Using the Adriamycin (ADR) mice model, cultured immortalized mouse podocytes were exposed to AS-IV. Western blotting, immunofluorescence, and histochemistry were used to analyze markers of autophagy, mitochondrial dysfunction, podocyte apoptosis, and glomerulopathy in the progression of focal segmental glomerular sclerosis. We observed that AS-IV can inhibit podocyte apoptosis, increased reactive oxygen species (ROS) generation, mitochondrial fragmentation, and dysfunction by inducing the Mfn2/Pink1/Parkin mitophagy pathway both in vivo and in vitro. Overexpression of Mfn2 reduced puromycin aminonucleoside (PAN)-induced podocyte injury, while downregulation of Mfn2 expression limited the renal protective effect of AS-IV by regulating mitophagy. AS-IV ameliorates renal function and renal pathological changes in ADR mice and inhibits PAN-induced podocyte injury by directly enhancing Mfn2/Pink1/Parkin-associated autophagy.

Nutritional and non-nutritional strategies in bodybuilding: Impact on kidney function

Bodybuilders routinely engage in many dietary and other practices purported to be harmful to kidney health. Thus, a structured narrative review of the literature was performed. The search strategy and parameters identifying areas of importance closely followed the PRISMA statement guidelines. This resulted in 13 relevant full-text articles consisting of 8 case reports and 5 case series, published since 2000. Kidney disease was described in 75 bodybuilders, with diagnoses ranging from acute kidney injury (AKI), acute tubular necrosis , focal segmental glomerular sclerosis (FSGS), nephrocalcinosis, acute interstitial nephritis , nephrosclerosis, chronic interstitial nephritis, an assortment of other glomerulonephritides. The development of AKI, FSGS and nephrocalcinosis may be particular risks. There is little evidence that high-protein diets and moderate creatine supplementation pose risks to individuals with normal kidney function though long-term high protein intake in those with underlying impairment of kidney function is inadvisable. The links between anabolic androgenic steroid use and FSGS are stronger, and there are undoubted dangers of nephrocalcinosis in those taking high doses of vitamins A, D and E. Dehydrating practices, including diuretic misuse, and NSAID use also carry potential risks. It is difficult to predict the effects of multiple practices carried out in concert. Investigations into subclinical kidney damage associated with these practices have rarely been undertaken. Future research is warranted to identify the clinical and subclinical harm associated with individual practices and combinations to enable appropriate and timely advice.

#1464 Alterations of podocytes in focal segmental glomerulosclerosis: a pilot study

Abstract Background and Aims The molecular features of idiopathic podocytopathies remain unexplored, preventing the development of effective therapies to control the mechanisms of disease initiation and progression. This includes idiopathic focal segmental glomerulosclerosis (FSGS), one of the most common forms of immune glomerulopathies (IG) and the cause of renal failure and replacement therapy. In FSGS, podocytes undergo pronounced cytoskeletal alterations. Along with a decrease in Wilms tumor protein (WT1) and α-SMA expression, there is evidence for increased expression of intermediate filament proteins (vimentin, desmin, nestin) and Wnt/β-catenin signaling upregulation in IG. Decrease in WT1 is associated with upregulation in Wnt/β-catenin and p53 to promote podocyte dysfunction and albuminuria. Upregulation desmin increases the mechanical stability of cells, allowing podocytes to undergo morphological changes on the tensile glomerular capillary wall. This pilot study was aimed to evaluate the significance of WT1, β-catenin, and desmin glomerular expression in early primary FSGS. Method We reviewed the histopathological and clinical data of patients with biopsy proven FSGS (N = 14, experimental group), IgA nephropathy (N = 12, positive control), without AKI, infectious diseases, heart failure, respiratory insufficiency and cancer pathology. Renal surgery specimens from patients without IG (N = 12) were studied as negative control. Glomerulosclerosis was assessed as percentage of all glomeruli. Mesangial lesions were measured semi-quantitatively in scores (0-3). Glomerular WT1, β-catenin, and desmin expression was assessed by IHC-P with quantitative morphometry of IHC-staining area (open software QuPath, Orbit Image Analysis). Molecule's co-expression was analyzed by IF-p and confocal microscopy (Zeiss LSM 710; study conducted in the Center for Collective Use “Confocal microscopy” by Pavlov Institute of Physiology Russian Academy of Sciences). Results We examined young and middle-aged patients with CKD stages 1-3 and moderate morphological changes in the glomeruli. Gender, age, eGFR and the percentage of glomeruli with segmental sclerosis were not significantly different between IG groups (all p for interaction &amp;gt;0.05). Patients with FSGS have lower levels of serum albumin (p &amp;lt; 0.001) and higher levels of proteinuria (p &amp;lt; 0.001) as compared to IgAN. Glomeruli from IgAN patients showed more mesangial cell proliferation (p = 0.001), expansion of the mesangial matrix (p = 0.05) and global glomerular sclerosis (p = 0.003) as compared to FSGS. An immunomorphological study showed lower WT1 expression in both IG groups compared to the negative control. In the IgAN, lower WT1 expression was associated with higher BC area (Fig. 1A, D). BC expression did not differ between FSGS and negative control (Fig. 1B,D). In the combined IG group, BC directly correlated with global (r = 0.63, p = 0.001) and segmental (r = 0.63, p = 0.001) glomerular sclerosis. In FSGS, a trend towards to increase in the area of desmin IHC-staining was detected, however, no significant differences between groups were found (Fig. 1C,D). BC and desmin were co-localized with the podocyte marker WT1 (Fig. 2). BC and desmin were also expressed in WT1-negative glomerular cells (Fig. 2). Differential molecular expression patterns in glomeruli have been identified. In IgAN, co-expressing WT1 and BC (orange) was dominate in glomerular cells (Fig. 2A); the proportion of IHC expression of WT1 and BC in glomerular cells was directly correlated (r = 0.63, p = 0.031). In FSGS, WT1+ cells predominantly co-expressed desmin (magenta) but not BC; some glomerular cells were only desmin-positive (Fig. 2B). BC was expressed to a lesser extent compared to IgAN, and in some cells it was co-expressed with desmin (Fig. 2B). Conclusion In FSGS, an increase in desmin expression could be an early feature of pathogenesis before significant decrease in the number of WT1+ podocytes and changes in β-catenin expression. Activation of desmin likely characterizes damage and decrease in the number of functioning podocytes.

#2862 Genetics and electron microscopy: complementary tools for management of focal segmental glomerulosclerosis?

Abstract Background and Aims Focal segmental glomerular sclerosis (FSGS) defines a histologic lesion that represents a pattern of injury associated to different pathologic conditions affecting both children and adults. It is classified into primary forms, presumably immune-mediated, secondary forms, determined by a maladaptive response to different conditions, genetic and undetermined forms. According to Mayo Clinic classification, primary and secondary forms can de differentiated using electron microscopy (EM), with a podocytes foot process effacement (FPE) ≥80% identifying primary forms. Better understanding the role of Genetics in FSGS and response to treatment in different forms is of vital importance in this rare and multifaceted condition. We analyzed a discrete cohort of patients with FSGS examined both with EM and genetic testing (GT). Main aims of our study were: 1) assessment of GT in primary and secondary forms; 2) analysis of response to therapy according to histologic and genetic classification. Method This is a retrospective observational study on patients that received a histological diagnosis of FSGS, including EM, and underwent NGS genetic testing from January 2020 to June 2023. Primary and secondary forms of FSGS were distinguished by degree of pedicle fusion at EM, according to Mayo Clinic classification. Clinical, laboratory, genetic data and used therapies were recorded. Complete response (CR) to therapy was defined as a reduction of proteinuria to 0.3 g/day, with normalization of albuminemia. Partial response (PR) was defined as halving proteinuria into a sub-nephrotic range and increasing albuminemia up to 3.5 g/dL. Absent response was defined as a persisting nephrotic range proteinuria. Results In the study period, 33 patients receiving a histologic diagnosis of FSGS with EM examination underwent NGS testing. Of these, 25 had available genetic results and were included. Ten patients (40%) were females, 15 (60%) were males; mean age was 40.8 years (SD ±14.5); 20 (80%) were Caucasian, 4 (16%) Black, 1 (4%) Asian. Based on EM, 11 (44%) were classified as primary forms, 14 (56%) as secondary forms. Twelve (48%) patients presented with nephrotic syndrome. Of these, 10 had a primary form. Seven (28%) had nephrotic-range proteinuria without hypoalbuminemia, 6 (24%) had subnephrotic range proteinuria. Six (54.5%) of the primary forms and 8 (57.1%) of the secondary forms had a positive genetic testing (p = 0.78). Among secondary forms, through GT, one diagnosis of Fabry disease and one of Tuberous Sclerosis were made in patients without clear systemic symptoms. Fabry disease was confirmed by presence of zebra bodies at EM. All primary forms received immunosuppressive therapies, all being rituximab-based regimens; all secondary forms received support therapy. Nine (81.1%) primary forms and 9 (64.3%) secondary forms had at least a PR to treatment (4 CR in primary group and 1 CR in secondary group) (p = 0.33). Among primary forms, 5 of 6 patients (83%) with a positive GT had at least a PR with a strong immunosuppressive therapy. In secondary forms group 4 of 8 patients (50%) had at least PR with offered support therapy. Fabry and Tuberous Sclerosis were offered specific treatments with benefit. Conclusion Percentage of positive GT did not differ in primary and secondary forms of FSGS as defined by Mayo Clinic classification. Thus a positive GT should not be considered a unique feature of secondary forms. GT was critical for an unexpected diagnosis of systemic hereditary diseases, thus enabling adequate target therapies. We believe GT should be offered to all patients with FSGS. In primary FSGS, defined according to EM, more than 80% of patients had at least a PR following immunosuppressive therapy, even in patients with positive GT. In conclusion, as clinical presentation and light microscopy are not sufficient for an accurate diagnosis, combining EM and GT is of utmost importance in proper classification and management of FSGS.

#2199 Kidney involvement aspects in women with Fabry disease from the Romanian cohort

Abstract Background and Aims Fabry disease (FD) is an X-linked rare lysosomal storage disease causing progressive nervous system, kidney and heart disorders. Progressive kidney impairment is common, and an important cause of morbidity and mortality. In FD females, treatment guidelines recommend therapy initiation when there is evidence of organ involvement, but determining the proper moment to start FD specific treatment could be a real challenge in the cases. The aim of our retrospective study is to investigate clinical and histological aspects of kidney involvement in female patients with genetically confirmed FD evaluated in our Expert Center for Rare Diseases of the Reno-Urinary System between 2015–2023, with focus on the clinical phenotype and initiation of FD specific treatment. Method All patients had comprehensive assessment for target organ manifestations of Fabry disease. Renal function was assessed using serum creatinine, albumin creatinine ratio and proteinuria. Also, 14 (40%) FD females underwent kidney biopsy (KB) in order to reveal the FD specific lesions and/or to establish the indication for FD pathogenic therapy. Kidney biopsy specimens were analyzed by light and electron microscopy. Results Our study included 35 heterozygous adult females with FD from 25 unrelated families. Most females (91.4%) were diagnosed through family screening, while 3 females (8.6%) were index cases. The mean age at diagnosis was 43.8 ± 15.3 years (range 17-73 years), although mean age of symptoms onset was 34.3 ± 13.5 years (range 14-61 years). Six women from our cohort were considered healthy carriers, three females presented only neurological manifestations, nine patients had combined renal and neurological involvement, one patient had cardiac and renal involvement and the others presented multiple organ involvement. Significant co-morbidities were: arterial hypertension in 13 patients, diabetes mellitus in 2 patients, and obesity in 9 patients. Overall baseline mean eGFR was 79.9 ± 28.2 (range 25-135) ml/min/1.73 m2. Eleven patients had no obvious kidney involvement, 10 patients presented chronic kidney disease (CKD) stage 2, 11 patients CKD stage 3, one CKD stage 4 and 1 was hemodialyzed. Seventeen patients presented normal UACR, thirteen patients showed microalbuminuria, and four patients presented macroalbuminuria. Overt proteinuria (&amp;gt; 0.3 g/24 h) was noticed in 8 patients. Thirteen females performed KB before the initiation of FD specific treatment, and one patient was already treated. At the moment of KB, five patients had normal biologic kidney assessment, three patients presented CKD stage 2 (microalbuminuria in 2 cases and proteinuria in 1 case), and five patients presented CKD stage 3 (normoalbuminuria in 1 case, microalbuminuria in 1 case and overt proteinuria in 3 cases). All KBs showed lysosomal accumulation in the podocytes, 92.8% showed inclusions in the parietal cells of the Bowman capsule, 85.7% in the tubules, while vascular inclusions were found in 78.5% of cases. Also, we observed segmental glomerular sclerosis in 5 cases, interstitial fibrosis and tubular atrophy in 3 cases, each. Only 2 patients were treated with pathogenic therapy before the first evaluation in our center. After multidisciplinary evaluation, 22 patients (62.8%) from our cohort received recommendation to initiate FD specific treatment, and 11 patients entered in our follow-up program. Evidence of specific FD lesions in KB was a strong reason to support the recommendation to initiate FD specific treatment. Conclusion Our results showed that kidney involvement in FD females can vary from asymptomatic or mildly symptomatic, to severely symptomatic, with end stage kidney disease. Thus, females should be carefully evaluated and monitored in a multidisciplinary team, in order to diagnosed FD affected organs. Also, we underline that a normal standard assessment of the kidney cannot rule out kidney involvement in female patients with FD, and strengthen the importance of KB for detection of early kidney involvement and for additional support for early initiation of FD specific therapy.

A new index for the outcome of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a common pathological form of nephrotic syndrome. This study analyzed the value of pathological lesions and clinical prognosis of different segmental glomerulosclerosis ratios in FSGS. Two hundred and six FSGS patients were collected from Dec 2013 to Apr 2016. The patients were divided into two groups according to the proportion of glomerular segmental sclerosis: F1 (SSR ≤ 15%, n = 133) and F2 (SSR > 15%, n = 73). The clinical and pathological data were recorded and analyzed, and statistical differences were observed between the serum uric acid level and the percentage of chronic renal failure. The pathological results showed significant differences in interstitial fibrosis and tubular atrophy (IFTA), degree of mesangial hyperplasia, vascular lesions, synaptopodin intensity, and foot process effacement between the two groups. Multivariate logistic regression analysis showed significant differences in creatinine (OR: 1.008) and F2 group (OR: 1.19). In all patients, the prognoses of urine protein and serum creatinine levels were statistically different. Multivariate Cox regression analysis revealed that F2 (hazard ratio: 2.306, 95% CI 1.022–5.207) was associated with a risk of ESRD (end stage renal disease). The proportion of segmental glomerulosclerosis provides a guiding value in the pathological diagnosis and clinical prognosis of FSGS.

Novel Pathogenic Mutation of P209L in TRPC6 Gene Causes Adult Focal Segmental Glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a leading kidney disease, clinically associated with proteinuria and progressive renal failure. The occurrence of this disease is partly related to gene mutations. We describe a single affected family member who presented with FSGS. We used high-throughput sequencing, sanger sequencing to identify the pathogenic mutations, and a systems genetics analysis in the BXD mice was conducted to explore the genetic regulatory mechanismsof pathogenic genes in the development of FSGS. We identified high urinary protein (++++) and creatinine levels (149μmol/L) in a 29-year-old male diagnosed with a 5-year history of grade 2 hypertension. Histopathology of the kidney biopsy showed stromal hyperplasia at the glomerular segmental sclerosis and endothelial cell vacuolation degeneration. Whole-exome sequencing followed by Sanger sequencing revealed a heterozygous missense mutation (c.643C > T) in exon 2 of TRPC6, leading to the substitution of arginine with tryptophan at position 215 (p.Arg215Trp). Systems genetics analysis of the 53 BXD mice kidney transcriptomes identified Pygm as the upstream regulator of Trpc6. Those two genes are jointly involved in the regulation of FSGS mainly via Wnt and Hippo signaling pathways. We present a novel variant in the TRPC6 gene that causes FSGS. Moreover, our data suggested TRPC6 works with PYGM, as well as Wnt and Hippo signaling pathways to regulate renal function, which could guide future clinical prevention and targeted treatment for FSGS outcomes.

Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review.

Graft loss from a living donor due to flash recurrence of focal segmental glomerular sclerosis — case report

Graft loss from a living donor due to flash recurrence of focal segmental glomerular sclerosis — case report

Functional Magnetic Resonance Imaging to Monitor Disease Progression: A Prospective Study in Patients with Primary Membranoproliferative Glomerulonephritis

Introduction: Primary membranoproliferative glomerulonephritis (MPGN) is a rare kidney disease with poor prognosis and no specific therapies. The disease heterogeneity and the difficulty of performing repeated kidney biopsies pose big challenges. This study investigates the correlation between non-contrast enhanced magnetic resonance imaging (MRI) and histologic and clinical findings in patients with primary MPGN. Methods: Patients with primary MPGN underwent baseline and 1-year kidney MRI in addition to biopsy and laboratory testing as part of a prospective MRI subproject of a clinical trial (ClinicalTrials.gov identifier NCT03723512). Diffusion-weighted and phase-contrast MRI were used to investigate kidney diffusivity and perfusion. Peritubular interstitial volume and fibrosis were quantified on kidney biopsies. Results: Seven patients with primary MPGN (18[17–21] years, 43% females) were included. Kidney biopsies showed variable degree of global and segmental glomerular sclerosis ([5–30]% and [10–60]%), mild interstitial fibrosis (<10%), and increased peritubular interstitial volume ([19–40]%). MRI and laboratory parameters changed very differently from patient to patient over 1 year. Peritubular interstitial volume and glomerular sclerosis negatively associated with renal blood flow (RBF) (rho = −0.81 and −0.77), and positively with renal vascular resistance (RVR) (rho = 0.65 and 0.73). Urinary albumin to creatinine ratio (uACR) negatively associated with RBF and filtration fraction (FF) (rho = −0.86 and −0.6), while positively with RVR (rho = 0.88). uACR decrease was associated with kidney diffusivity increase (rho = −0.5). Measured glomerular filtration rate (GFR) positively associated with kidney diffusivity, RBF, and FF (rho = 0.87, 0.85, and 0.59), while negatively with RVR (rho = −0.89); GFR increase was associated with kidney diffusivity, RBF, and FF increase (rho = 0.77, 0.7, and 0.7) and RVR decrease (rho = −0.7). Conclusion: The strong correlation found between MRI and histologic and clinical findings, despite the rather limited number of patients, highlights MRI potential to monitor disease progression in patients with rare kidney disease.

Clinical and pathological correlation between urinary exosome miR-223 and IgAN patients.

To investigate the association between urine exosome miR-223 and clinical markers with pathological severity of IgA nephropathy (IgAN) in order to offer a new perspective for the evaluation of IgAN patients. Western blotting and transmission electron microscopy were used to identify the exosomes collected and isolated from subjects' urine. qRT-PCR was then performed to determine the expression level of miR-223. Following that, the relationship between miR-223 expression, clinical markers, and the severity of pathology in IgAN patients was examined. (1) Urine can be used to isolate exosomes since its marker protein was visible by Western blotting, and its size and structure were observable using transmission electron microscopy. (2) Expression levels of miR-223 in urinary exosomes were much higher in IgAN patients than in healthy subjects, and these were also positively correlated with creatinine (Cr) (rho=0.396; p=0.006), blood urea nitrogen (BUN) (rho=0.371; p=0.011), 24-hour urinary microalbumin (24hU-mALB) (rho=0.341; p=0.036), mesangial cell proliferation (rho=0.359; p=0.014), glomerular segmental sclerosis (rho=0.417; p=0.004), cell/fibroblast crescents (rho=0.612; p=0.000), glomerulosclerosis, and renal interstitial fibrosis (rho=0.331; p=0.025). In urine exosomes, miR-223 might be considered a non-invasive biomarker for the assessment of IgAN disease progression.

Calcineurin inhibitors or cyclophosphamide in the treatment of membranous nephropathy superimposed with FSGS lesions: a retrospective study from China

Background Cyclophosphamide (CTX) and calcineurin inhibitors (CNIs) based regimens are recommended as immunosuppressive therapies for patients with idiopathic membranous nephropathy (IMN). Focal and segmental glomerular sclerosis (FSGS) lesions, which are common in membranous nephropathy (MN), are poor predictors of outcome. This study compared the differences of prognosis between two regimens in patients with IMN combined with FSGS lesions. Methods This retrospective study enrolled 108 patients with biopsy-proven IMN, accompanied with FSGS lesions, nephrotic syndrome and an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 who were treated with CTX or CNIs. We used propensity score matching (PSM) for balancing the confounding variables. Results During follow-up, 10 patients (10/55 [18.2%]; nine males) in the CNIs group showed a 50% decline in eGFR; eight had a not otherwise specified variant. Patients initially treated with CNIs had a significantly higher risk of progression to the primary outcome and a lower probability of complete or total remission. The relapse rate was higher in patients who initially received CNIs- than in those who received CTX-based treatment. Before PSM, age and 24-h urine protein level differed significantly between the groups. The PSM model included data from 72 patients. Worse outcomes were also noted among patients who initially received CNIs than those who received CTX-based treatments after matching. Conclusions Patients with MN combined with FSGS lesions have a higher risk of renal functional decline and a higher rate of relapse after CNIs than after CTX therapy.

Stage lighting on PAR-1: a step further in the understanding of acquired focal and segmental glomerulosclerosis

The pathogenic mechanisms of acquired focal and segmental glomerular sclerosis are only partially known and represent a medical challenge in nephrology. The article by May etal. sheds additional light on previous data indicating the key role of the protease-activated receptor 1. The new evidence is based on invivo studies in relevant animal models and on patient biopsies and represents a significant step forward in the understanding of this pathologic condition.

Long-term follow-up of IgA nephropathy: clinicopathological features and predictors of outcomes.

The establishment of the Oxford classification and newly developed prediction models have improved the prognostic information for immunoglobulin A nephropathy (IgAN). Considering new treatment options, optimizing prognostic information and improving existing prediction models are favorable. We used random forest survival analysis to select possible predictors of end-stage kidney disease among 37 candidate variables in a cohort of 232 patients with biopsy-proven IgAN retrieved from the Norwegian Kidney Biopsy Registry. The predictive value of variables with relative importance >5% was assessed using concordance statistics and the Akaike information criterion. Pearson's correlation coefficient was used to identify correlations between the selected variables. The median follow-up period was 13.7 years. An isolated analysis of histological variables identified six variables with relative importance >5%: T %, segmental glomerular sclerosis without characteristics associated with other subtypes (not otherwise specified, NOS), normal glomeruli, global sclerotic glomeruli, segmental adherence and perihilar glomerular sclerosis. When histopathological and clinical variables were combined, estimated glomerular filtration rate (eGFR), proteinuria and serum albumin were added to the list. T % showed a better prognostic value than tubular atrophy/interstitial fibrosis (T) lesions with C-indices at 0.74 and 0.67 and was highly correlated with eGFR. Analysis of the subtypes of segmental glomerulosclerosis (S) lesions revealed that NOS and perihilar glomerular sclerosis were associated with adverse outcomes. Reporting T lesions as a continuous variable, normal glomeruli and subtypes of S lesions could provide clinicians with additional prognostic information and contribute to the improved performance of the Oxford classification and prognostic tools.