The origin of albuminuria remains controversial owing to difficulties in quantifying the actual amount of albumin filtered by the kidney. Here we use fluorescently labeled albumin, together with the ...powerful technique of intravital 2-photon microscopy to show that renal albumin filtration in non-proteinuric rats is ~50 times greater than previously measured and is followed by rapid endocytosis into proximal tubule cells (PTCs). The endocytosed albumin appears to undergo transcytosis in large vesicles (500nm in diameter), identified by immunogold staining of endogenous albumin by electron microscopy, to the basolateral membrane where the albumin is disgorged back to the peritubular blood supply. In nephrotic rats, the rate of uptake of albumin by the proximal tubule (PT) is decreased. This is consistent with reduced expression of clathrin, megalin, and vacuolar H+-ATPase A subunit, proteins that are critical components of the PT endocytotic machinery. These findings strongly support the paradigm-shifting concept that the glomerular filter normally leaks albumin at nephrotic levels. Albuminuria does not occur as this filtered albumin load is avidly bound and retrieved by PTCs. Dysfunction of this retrieval pathway leads to albuminuria. Thus, restoration of the defective endocytotic and processing function of PT epithelial cells might represent an effective strategy to limit urinary albumin loss, at least in some types of nephrotic syndrome.
Atypical haemolytic uraemic syndrome and steroid-resistant nephrotic syndrome are highly rare kidney diseases that can occur in childhood. In some cases, genetic variants may trigger these ...conditions, although in atypical haemolytic uraemic syndrome they mostly confer only a predisposition to the disease. Most variants causing atypical haemolytic uraemic syndrome were identified in genes encoding proteins regulating the complement pathway; on the other hand, there are approximately 58 genes encoding distinct proteins primarily causing steroid-resistant nephrotic syndrome. We present a child with steroid-resistant nephrotic syndrome and a confirmed homozygous c.966G > A, p.Trp322Ter pathogenic variant in DGKE. This variant was also found in compound with a novel DGKE heterozygous deletion c.171delG, p.Ser58Alafs*111 in a patient from our paediatric cohort with atypical haemolytic uraemic syndrome. Both cases presented with hypertension, nephrotic proteinuria and severe acute kidney injury followed by renal recovery; however, their renal histology was different. In this paper, we deal with the clinical course of children with disrupted DGKE, including the steroid-resistant nephrotic syndrome and atypical haemolytic uraemic syndrome overlap.
To summary the clinical presentation and prognosis of primary nephrotic syndrome (PNS) in teenagers.
The clinical data, renal pathological types and prognosis of 118 children over 10-year-old with ...PNS treated in the Department of Nephrology of the Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to December 2020 were retrospectively analyzed, with 408 children ≤10-year-old as control group synchronously. Chi-square test was used to compare the difference of clinical types, pathologic types, response to steroids and tubulointerstitial changes between the groups. The teenagers with steroid resistant nephrotic syndrome (SRNS) were divided into initial non-responder group and late non-responder group. Kaplan-Meier method was used to compare the difference of persistent proteinuria, and Fisher's exact test for the histological types.
There were 118 children >10-year-old, including 74 males and 44 females, with the onset age of 12.1 (10.8, 13.4) years; and 408 children ≤10-year-ol
To analyze the frequency and nature of hemorrhagic and thrombotic complications in patients with systemic AL-amyloidosis and compare with laboratory changes in the hemostasis system.
The prospective ...study included 40 patients with newly diagnosed AL-amyloidosis. To detect amyloid, all patients underwent bone marrow trephine biopsy and duodenal biopsy, and 28 (70%) patients underwent biopsy of the affected organ. Before the start of therapy, all patients were determined the platelet count, activated partial thromboplastin time, thrombin time, fibrinogen concentration, time of XIIa-dependent fibrinolysis, antithrombin III, D-dimer, activity of blood coagulation factors VIII, X and vWF. The statistical part of the study was carried out using the IBM SPSS Statistics 2017 system software (SPSS, Chicago, IL, USA).
In 20 (50%) patients, hemorrhages on the skin and mucous membranes were diagnosed as vascular purpura. Before the start of therapy, 7 (17.5%) patients had thrombosis, including leg vein thrombosis (5 patients), ischemic stroke (2 patients). There was a direct correlation between thrombotic complications and cutaneous hemorrhagic syndrome (
=0.007). In 15 (75%) cases, cutaneous hemorrhagic syndrome was accompanied by hypercoagulable shifts in the hemostasis system. Of the 20 patients with cutaneous hemorrhagic syndrome, 19 (95%) patients had kidney damage, including 15 patients with nephrotic syndrome. Hematoma type of bleeding, as well as heavy bleeding was not observed, including after a biopsy of the internal organs. According to the totality of hemostasis indicators, hypercoagulation syndrome was more often observed (in 23; 56% of patients). Hypocoagulation was diagnosed only in 2 (5%) patients with liver damage, 16 (39%) patients had normocoagulation.
Cutaneous hemorrhagic syndrome is the most common clinical manifestation of disorders in the hemostasis system in patients with AL-amyloidosis. The relationship of hemorrhages on the skin with nephrotic syndrome has been established, which may indicate a single pathogenetic mechanism. Cutaneous hemorrhagic syndrome is associated with hypercoagulable shifts in hemostasis and a high risk of thrombotic complications.
Kimura disease (eosinophilic granuloma of the soft tissue) is a benign granulomatous disease complicated by nephrotic syndrome. Herein, we report a case of recurrent minimal change nephrotic syndrome ...(MCNS) complicated by Kimura disease that was successfully treated with rituximab. A 57-year-old man presented to our hospital with relapsed nephrotic syndrome with worsening swelling of the right anterior ear and elevated serum IgE. MCNS was diagnosed on renal biopsy. Treatment with 50 mg of prednisolone rapidly placed the patient in remission. Therefore, RTX 375 mg/m
2
was added to the treatment regimen, and steroid therapy was tapered. Early steroid tapering was successful, and the patient is currently in remission. In this case, the nephrotic syndrome flare-up was accompanied by worsening Kimura disease. Rituximab reduced the worsening of symptoms related to Kimura disease, including head and neck lymphadenopathy and elevated IgE levels. Kimura disease and MCNS may share a common IgE-mediated type I allergic condition. Rituximab effectively treats these conditions. In addition, rituximab suppresses Kimura disease activity in patients with MCNS, enables early tapering of steroids, and reduces the total dose of steroids.
Background: Chylothorax can be classified into traumatic and nontraumatic based on the etiology. Nephrotic syndrome is a very rare cause of nontraumatic chylothorax in adults. Case presentation: A ...66-year-old woman with membranous nephropathy who was non-compliant with her management, presented with dyspnea, and was found to have a large right sided chylothorax. Her chylothorax was secondary to membranous nephropathy after excluding other causes, which has been rarely reported in literature. Conclusion: This case highlights the possibility of nephrotic syndrome causing chylothorax, especially in patients with undiagnosed nephrotic syndrome or patients non-compliant with their management. When evaluating a patient with chylothorax, providers should consider nephrotic syndrome in the differential diagnosis.
Background
Prospective research of children receiving heterogeneous vaccines has shown that immunization is not associated with pediatric idiopathic nephrotic syndrome (NS) relapses. However, ...prospective data concentrating only on influenza (flu) virus vaccines are not available.
Methods
This multicenter prospective study was conducted in children with NS who received inactivated flu vaccines from June 2017 to July 2018. The day of flu vaccination was defined as day 0, and the period between prevaccination and postvaccination days was defined as −
X
to +
Y
(period from day − 180 to 0 as the precontrolled period). The primary outcome was the NS relapse rate from day 0 to + 30 as a direct association with vaccination compared with those in the precontrolled period. Exacerbation was defined as children experiencing more NS relapses after vaccination compared with those in the precontrolled period, or children starting any new immunosuppressants due to NS relapse after vaccination.
Results
Sixty-three children were included. Relapse rates were not significantly different between the precontrolled period and 0 to + 30 periods (0.38 vs. 0.19 times/person-year,
p
= 0.95). Although the exacerbation rate during the 0 to + 180 period in children without NS relapse in the precontrolled period was very low (4/54 7.4 %), children with at least one NS relapse in the precontrolled period showed a remarkable increase in the rate (4/9 44.4%;
p
= 0.01).
Conclusions
Flu vaccination did not significantly precipitate the direct relapse of NS in children. However, it might increase the disease activity in children with at least one NS relapse within a half year before vaccination.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
PCSK9 in chronic kidney disease Pavlakou, P.; Liberopoulos, E.; Dounousi, E. ...
International urology and nephrology,
06/2017, Letnik:
49, Številka:
6
Journal Article
Recenzirano
Purpose
Chronic kidney disease (CKD) is accompanied by a number of secondary metabolic dysregulations, such as lipid abnormalities, presenting with unique characteristics. Proprotein convertase ...subtilisin/kexin 9 (PCSK9) inhibitors have been introduced as the new era in the management of dyslipidemia with promising results in groups with refractory lipid abnormalities. Increasing number of studies investigate the possible association of PCSK9 levels with kidney function, especially with nephrotic range proteinuria, as well as its role as a prognostic cardiovascular risk marker in CKD. In this review, we discuss the existing evidence for PCSK9 levels in patient groups with nephrotic syndrome, non-dialysis CKD, end-stage renal disease and kidney transplantation.
Methods
Online research was conducted in MEDLINE database to identify articles investigating PCSK9 in all different aspects of CKD. References from relevant studies were screened for supplementary articles.
Results
Four cross-sectional studies, one secondary analysis, one publication from two independent cohort studies and one multicentre prospective cohort study assessed PCSK9 plasma levels in different subgroups of CKD patients. PCSK9 levels increase in nephrotic syndrome and have a positive correlation with proteinuria. In CKD patients, no correlation was found between PCSK9 levels and estimated GFR. Peritoneal dialysis patients have higher PCSK9 levels compared with hemodialysis and renal transplant patients as well as general population.
Conclusion
Accumulative evidence focuses on the possible association of PCSK9 levels with kidney function. No data are available for the administration of PCSK9 inhibitors in CKD patients. Further research will optimize knowledge on the role of PCSK9 levels and PCSK9 inhibitors in CKD.
Background
Long-term outcomes of children with nephrotic syndrome have not been well described in the literature.
Methods
Cross-sectional study data analysis of
n
= 43 patients with ...steroid-sensitive (SSNS) and
n
= 7 patients with steroid-resistant (SRNS) nephrotic syndrome were retrospectively collected; patients were clinically examined at a follow-up visit (FUV), on average 30 years after onset, there was the longest follow-up period to date.
Results
The mean age at FUV was 33.6 years (14.4–50.8 years,
n
= 41). The mean age of patients with SSNS at onset was 4.7 years (median 3.8 years (1.2–14.5 years), the mean number of relapses was 5.8 (0 to 29 relapses). Seven patients (16.3%) had no relapses. Eleven patients were “frequent relapsers” (25.6%) and four patients still had relapses beyond the age of 18 years. Except of cataracts and arterial hypertension, there were no negative long-term outcomes and only one patient was using immunosuppressant therapy at FUV. 55% of patients suffered from allergies and 47.5% had hypercholesterolemia. Two patients suffered a heart attack in adulthood. A younger age at onset (< 4 years) was a risk factor for frequent relapses. An early relapse (within 6 months after onset) was a risk factor and a low birth weight was not a significant risk factor for a complicated NS course. The mean age of patients with SRNS at onset was 4.6 ± 4.4 years and 27.5 ± 9.9 years at FUV. Three patients received kidney transplantations.
Conclusions
The positive long-term prognosis of SSNS can reduce the concern of parents about the probability of the child developing a chronic renal disease during the clinical course after onset.
Over the past decade, genome-wide association studies (GWAS) have emerged as a powerful tool to understand the genetic basis of complex traits in humans. The GWAS approach has been successfully ...applied to primary glomerular disorders, providing numerous novel insights into the genetic architecture of IgA nephropathy, membranous nephropathy, and steroid-sensitive nephrotic syndrome. IgA nephropathy appears to have a highly complex polygenic architecture, with nearly 20 genome-wide significant loci of small-to-moderate effects discovered to date. In contrast, the genetic susceptibility to membranous nephropathy and steroid-sensitive nephrotic syndrome appears to be driven by a small number of large-effect loci. The MHC locus on chromosome 6p21 is strongly associated with genetic susceptibility to all major types of immune-mediated glomerulopathies. However, a distinct set of classical HLA alleles is associated with each individual disease type, pinpointing to specific immune mechanisms underlying each of these conditions. Additional insights from the discovery of non-HLA risk loci reinforced the role of innate and adaptive immunity in the pathogenesis of these disorders, and highlighted important susceptibility overlaps between glomerular and other autoimmune and inflammatory conditions. Despite these initial successes, much larger GWAS and sequencing studies are still needed for each individual glomerular disease type. Increased power will be critical to comprehensively test for genetic effects across the full spectrum of allelic frequencies, to detect gene-gene and gene-environment interactions, and to potentially improve the performance of polygenic risk predictors. Moreover, the existing studies are limited mostly to European and East Asian populations, stressing the urgency to expand genetic discovery efforts to more diverse populations worldwide.
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