Nephrotic Syndrome Patients Research Articles

Rapid Molecular Evaluation of Human Kidney Tissue Sections by In Situ Mass Spectrometry and Machine Learning to Classify the Nephrotic Syndrome.

Nephrotic syndrome (NS) is classified based on morphological changes of glomeruli in biopsied kidney tissues evaluated by time-consuming microscopy methods. In contrast, we employed desorption electrospray ionization mass spectrometry (DESI-MS) directly on renal biopsy specimens obtained from 37 NS patients to rapidly differentiate lipid profiles of three prevalent forms of NS: IgA nephropathy (n = 9), membranous glomerulonephritis (n = 7), and lupus nephritis (n = 8), along with other types of glomerular diseases (n = 13). As we noted molecular heterogeneity in regularly spaced renal tissue regions, multiple sections from each biopsy specimen were collected, providing a total of 973 samples for investigation. Using multivariate analysis, we report differential expressions of glycerophospholipids, sphingolipids, and glycerolipids among the above four classes of NS kidneys, which were otherwise overlooked in several past studies correlating lipid abnormalities with glomerular diseases. We developed machine learning (ML) models with the top 100 features using the support vector machine, which enabled us to discriminate the concerned glomerular diseases with 100% overall accuracy in the training, validation, and holdout test set. This DESI-MS/ML-based tissue analysis can be completed in a few minutes, in sharp contrast to a daylong procedure followed in the conventional histopathology of NS.

Long-term visit-to-visit variability in low-density lipoprotein cholesterol is associated with poor cardiovascular and kidney outcomes in patients with primary nephrotic syndrome.

It is unclear whether long-term variability in low-density lipoprotein cholesterol (LDL-C) is associated with clinical outcomes in patients with nephrotic syndrome (NS). A large cohort of 1100 patients with primary NS underwent treatment and regular follow-up. Long-term variability in LDL-C was assessed by calculating its weighted standard deviation (w-SD). The primary endpoints of this study were the occurrence of arteriosclerotic cardiovascular disease (ASCVD) or kidney dysfunction. Factors associated with the w-SD of LDL-C were evaluated by linear regression. Associations of the w-SD of LDL-C with clinical outcomes were evaluated by Cox proportional hazards regression. Over a median follow-up of 44.8 (interquartile range, 26.8, 70.1) months, 198 patients developed ASCVD (45.9 cases per 1,000 patient-years), and 84 patients developed kidney dysfunction (17.6 cases per 1,000 patient-years). The incidence rates of the primary outcomes increased across the quartiles of the w-SD of LDL-C (log-rank, P < 0.001). Multivariate Cox regression analysis showed that higher LDL-C variability was associated with an increased risk of ASCVD [hazard ratio (HR), 2.236; 95% confidence interval (CI), 1.684-2.969, P < 0.001] and an increased risk of kidney dysfunction (HR, 3.047; 95% CI 2.240-4.144, P < 0.001). The results were similar after adjusting the w-SD of LDL-C by its related parameters (baseline and mean LDL-C as well as mean total cholesterol), although the mean LDL-C was also an independent risk factor for ASCVD and kidney dysfunction. Long-term variability in LDL-C was independently associated with the risk of ASCVD and kidney dysfunction in NS patients.

Does Urinary Vitamin D-Binding Protein Have a Role in the Prediction of Steroid Resistance in Nephrotic Syndrome? A Cohort Study on Egyptian Children

Background: Nephrotic syndrome (NS) is a common glomerular disease in children, for which there are currently no noninvasive markers for predicting responsiveness to steroid treatment. Objectives: This study aimed to analyze the relationship between clinical-laboratory presentations and subsequent response to steroid therapy and to evaluate the role of urinary vitamin D binding protein (uVDBP) as a predictor of steroid resistance (SR). Methods: This was a prospective longitudinal study on 60 children with active NS (30 patients with newly diagnosed NS and 30 with relapsed NS). In addition, 30 control subjects served as a reference group for uVDBP values. The patients were evaluated before starting steroid therapy, and response to steroid therapy was monitored 4 - 8 weeks later. Results: The levels of uVDBP were elevated in patients with NS (33.33 ± 15.6 ng/mL) compared to control subjects (17.35 ± 5.5 ng/mL, P &lt; 0.001). Also, the levels of uVDBP were significantly higher in patients with relapsed NS (37.93 ± 16.2 ng/mL) than in newly diagnosed NS patients (28.73 ± 13.67 ng/mL, P = 0.014). The level of uVDBP on presentation did not significantly differ between patients who had steroid-sensitive nephrotic syndrome (SSNS) (34.91 ± 15.01 ng/mL) and patients who had steroid-resistant nephrotic syndrome (SRNS) after 4 - 8 weeks of steroid treatment (32.60 ± 15.94 ng/mL, P = 0.417). Steroid resistance was significantly associated with a younger age of onset, specifically below 2.1 years (P = 0.023), a longer duration of the illness (P = 0.007), having more relapses (P = 0.002), total leucocytic count on presentation &gt; 8.05 × 103/mm3 (P = 0.031), and platelet counts on presentation &gt; 516.5 × 103/mm3 (P = 0.044). Conclusions: In this study, we found that uVDBP levels could reflect disease severity rather than predict the pattern of steroid responsiveness. Younger age of onset, longer duration of illness, previous relapses, and increased total leukocyte and platelet counts on presentation were associated with SRNS.

Oral Health Status of Children with Special Healthcare Need: A Retrospective Analysis.

To evaluate the oral health status of children with special healthcare needs (CSHCN) having either systemic illness or any disabilities. A retrospective analysis of oral health status was done from Jan 2013 to Dec 2018 on 58 CSHCN (both genders) up to 16 years of age. The oral health status of patients was assessed with the decayed, missing, and filled teeth (DMFT/dmft) indices and simplified oral hygiene index (OHI-S) by using the World Health Organization (WHO) 2013 oral health survey criteria. Fair oral hygiene was dominantly present (62%) among all the subjects. Association between oral hygiene status and systemic illness/disability was done using the Chi-squared (χ 2 ) test and was found statistically nonsignificant. The overall mean DMFT/dmft found was 4.16. The highest mean DMFT/dmft score was recorded in nephrotic syndrome patients (16.0%), while the least score was seen among cleft anomalies (1.89%). Comparison between mean DMFT/dmft scores among various systemic illnesses/disabilities were done using Kruskal-Wallis one-way analysis of variance (Kruskal-Wallis ANOVA) test and found statistically significant (p-value 0.048). The majority of the CSHCN fall under fair oral hygiene status. A high caries prevalence and statistically significant value were demonstrated between mean DMFT/dmft scores of various systemic illnesses/disabilities. Present study aids in understanding the needs of the community, identifying high-risk groups, planning the required treatment and prevention strategies, and thus monitoring and improving the oral health status of children with special healthcare needs. Patidar D, Sogi S, Patidar DC. Oral Health Status of Children with Special Healthcare Need: A Retrospective Analysis. Int J Clin Pediatr Dent 2022;15(4):433-437.

T-cell and B-cell repertoire diversity are selectively skewed in children with idiopathic nephrotic syndrome revealed by high-throughput sequencing.

Clinical studies suggest that the dysfunction of T cells and B cells may play an essential role in the pathogenesis of idiopathic nephrotic syndrome (INS), but laboratory evidence is lacking. Therefore, this study explored T-cell receptor (TCR) and B-cell receptor (BCR) profiling in children with idiopathic nephrotic syndrome. High-throughput sequencing technology was used to profile the TCR and BCR repertoires in children with INS. Peripheral blood was collected from ten INS patients, including five vinculin autoantibody-positive patients and five vinculin autoantibody-negative patients, before and after treatment. TCR and BCR libraries were constructed by 5'-RACE and sequenced by a DNBSEQ-T7 sequencer, and sequence analyses were performed using ReSeqTools, FastP, MiXCR, and VDJtools. The TRA (T-cell receptor α), TRG (T-cell receptor γ), and IGH (immunoglobulin heavy chain) repertoires of the INS group were occupied by highly abundant clonotypes, whereas small clonotypes occupied the healthy group, especially TRA. A significant increase in the Shannon-Weaver index was observed for the TRA and TRG repertoires after treatment in vinculin autoantibody-negative patients, but a significant increase in the IGH repertoire after treatment was observed in vinculin autoantibody-positive patients. The frequency of some V-J pairs was significantly enriched in steroid-sensitive nephrotic syndrome patients. The usage frequency of the V and J genes was skewed in patients, which seemed not related to immunosuppressive therapy. However, after effective treatment, dynamic changes in the size of the individual clonotype were observed. T-cell and B-cell immunity contribute to the pathogenesis of different INSs. Video: (MP4 99,786KB).

B-cell activating factor (BAFF) and its receptors' expression in pediatric nephrotic syndrome is associated with worse prognosis.

Immune pathogenesis of nephrotic syndrome (NS) is not completely understood. We aimed to evaluate the expression of B-cell activating factor (BAFF) and its receptors in renal samples from pediatric NS patients and its relationship with renal function survival. We conducted an ambispective study on 33 patients with pediatric NS. Immunohistochemistry for BAFF, TACI, BCMA and BR3 was performed. Markers were evaluated on podocytes and interstitial inflammatory infiltrates (III). We performed Kaplan-Meier curves to describe renal function survival according to markers' expression. Thirty-three NS patients were included. Minimal change disease was seen in 21 (63.6%) patients, and focal segmental glomerulosclerosis in 12 (36.4%). BAFF was found in podocytes (18.2% of samples) and III (36.4% of samples), BAFF-R in one sample, TACI in 4 (podocytes and III), and BCMA in 5 samples of podocytes and 7 of III. BAFF on podocytes and III was associated with worst renal function at follow-up; those patients had 25% probability of having GFR >90 mL/min/1.73m2, versus 84.9% when absent (p = 0.0067). Patients with BAFF in III had 42.9% probability of having GFR>90 mL/min/1.73 m2, versus 94.1% when absent (p = 0.0063). BAFF expression in renal biopsies could be a prognostic factor for renal function.

Thrombodynamics as a tool for monitoring hemostatic disorders in patients with chronic glomerulonephritis complicated by nephrotic syndrome.

To assess hemostatic disorders in CGN patients complicated by NS using the thrombodynamics test. The study included 60 adult patients with chronic glomerulonephritis (CGN), mean age 37 years, 31 (52%) women, and 29 (48%) men. Among all patients, 53 % of patients had NS, 47 % had no sign of NS. Hemostasis was assessed using the thrombodynamics test. The results were compared with biochemical parameters, which are usually associated with NS and renal dysfunction. According to the thrombodynamics test, CGN patients with NS demonstrated a tendency to hypercoagulability: increased rates of V (rate of clot growth), increased D (clot density), and increased CS (clot size) after 30 minutes. A positive correlation of these parameters with the serum albumin, creatinine levels, and glomerular filtration rate (GFR) indicates the influence of severe NS and renal dysfunction on the hemostasis activation in CGN patients with NS. According to the thrombodynamics test, CGN patients with NS demonstrate increased rates of clot formation, increased clot size after 30 minutes, and increased clot density due to secondary hemostasis activation. These changes positively correlate with the severity of hypoalbuminemia, hypercholesterolemia, and renal dysfunction in NS patients.

The quantifying relationship between the remission duration and the cardiovascular and kidney outcomes in the patients with primary nephrotic syndrome

Background Patients with persistent nephrotic-range proteinuria have a high risk of kidney dysfunction and cardiovascular events. Recently, the maintenance of proteinuria remission has been demonstrated to reduce the risk of kidney endpoint. However, the effect of remission duration on cardiovascular outcomes remains unclear. Methods This study enrolled 982 patients with primary nephrotic syndrome who had achieved clinical remission. Remission duration was defined as the maintenance time (months) of the first remission. Arteriosclerotic cardiovascular disease (ASCVD) and kidney dysfunction (ESKD or eGFR reduction >50%) were the endpoints. Survival curves, Cox regression models, restricted cubic spline analysis were used and the cutoff time points were determined. Results During the 38.3 months of follow-up, 161 (16.4%) patients developed ASCVD (51.3 per 1000 patient-years) and 52 (5.3%) patients developed kidney dysfunction (15.3 per 1000 patient-years). Multivariate analysis showed that remission duration was an independently protective factor to ASCVD, in which each one-year extension associated with a 15% reduction of the risk (HR, 0.854; 95% CI, 0.776 ∼ 0.940, p = .001). The initial time point was seven months for remission to present the protective effect to ASCVD and the maximum time point was 36 months. Remission duration was also an independently protective factor to kidney dysfunction. This effect was shown from the beginning of remission and reached the maximum at 26 months. Conclusions The maintenance of proteinuria remission was crucial for the improvement of cardiovascular and kidney outcomes in nephrotic syndrome patients.

NURTuRE-INS: A Biobank of United Kingdom Idiopathic Nephrotic Syndrome Patients to Enable Research and Disease Stratification

NURTuRE-INS: A Biobank of United Kingdom Idiopathic Nephrotic Syndrome Patients to Enable Research and Disease Stratification

Safety and Effectiveness of Direct Xa Inhibitors vs Warfarin in Patients with Nephrotic Syndrome

Introduction: Nephrotic syndrome (NS) is characterized by excessive proteinuria (&gt; 3.5 g/day), hypoalbuminemia, and edema. Objectives: The main objective of the study is to find the safety and effectiveness of direct Xa inhibitors vs warfarin in patients with nephrotic syndrome. Material and methods: This cross-sectional study was conducted in Akbar Niazi Teaching Hospital, Barakahu, Islamabad from January 2022 till June 2022. The data were collected from 120 patients which diagnosed with nephrotic syndrome. After permission from hospital ethical committee, total 120 patients meeting the inclusion and exclusion criteria was enrolled in the study. Detailed history of kidney disease and physical examination was done to meet the inclusion and exclusion criteria. Informed consent was obtained. Results: The data was collected from 120 patients. Out of 120 participants, 60 were treated with warfarin while 60 were considered as control group. Median age was 26 years in group I and 25.3 years in group II (p=0.705). Female cases counted for 41 (86%) and 19 (14%) in I and II groups, respectively. Risk factors, clinical presentation, affected vessels and AF for both groups are depicted in Table I. Results from both groups were comparable and statistically, no significant differences were observed (p• value more than 0.05). Practical implication: This study will help in treating nephrotic syndrome and kidney complications. Conclusion: It is concluded that awareness about nephrotic syndrome in patients were low and its prevalence continues to remain high and is likely to increase globally. Direct Xa inhibitors were associated with lower hazards of kidney complications and mortality than warfarin in patients with nephrotic syndrome. Keywords: Nephrotic, Syndrome, Complications, Mortality, Warfarin

Evaluation of corneal and lens densitometry with Pentacam HR in children with Nephrotic Syndrome: A controlled, prospective study

BackgroundThis study aimed to compare the corneal and lens densitometry values between children with Nephrotic Syndrome (NS) and healthy individuals. MethodsThis cross-sectional comparative study included 23 patients with NS and 26 healthy controls. Corneal topographic and corneal and lens densitometric values were measured using Pentacam HR. Densitometry measurements in different layers were analyzed and compared between groups. Correlations between steroid cumulative dose, age at diagnosis of the disease, duration of disease, number of relapses, and patients' densitometries values were evaluated. ResultsThe measurements of the keratometry, horizontal white-to-white, and iridocorneal angle values were significantly different between groups (p < 0.05). The 0–2 mm and 2–6 mm anterior corneal densitometry values were significantly higher in NS patients. (p = 0.009 and p = 0.033, respectively). The lens densitometry values of all zones were higher in the eyes with NS but there was no statistically significant difference from the healthy control eyes (p > 0.05). There was a positive strong correlation between the cumulative steroid dose and the posterior lens zone densitometry, a positive weak correlation between the number of attacks and anterior corneal densitometry, and between disease duration and central corneal densitometry and average lens density. ConclusionIn eyes with NS, changes occur in corneal and lens densitometry in correlation with disease duration, number of attacks, and cumulative steroid dose. Significant density changes were detected especially in the anterior cornea and central 0–6 mm area.

Evaluation of the Rationality of Appropriate Doses of Corticosteroid Drugs in Patients With Nephrotic Syndrome in Hospitals

Nephrotic syndrome is a kidney disease in which symptoms include massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Nephrotic syndrome has first-line therapy using corticosteroids. The purpose of this study was to determine the accuracy of the dose in patients with nephrotic syndrome. The method used in this study is a qualitative descriptive method of retrospective data acquisition by taking a sample population of nephrotic syndrome patients at the Outpatient Installation of General Hospital of Ciamis District Period January-July 2020. Descriptive analysis includes the accuracy of the dose guided by the management of Kidney Disease: Improving Global Outcomes (KDIGO) which is presented in the form of tables and narratives. The results of this study indicate that the ratio between men and women is 3:1 with those under 15 years old. There were 18 cases of nephrotic syndrome using corticosteroid therapy. The most widely used corticosteroids were methylprednisolone 61.1% (11 patients) and prednisone 38.9% (7 patients). The use of the dose in 18 cases of nephrotic syndrome was stated to be the right dose (100%) and in accordance with the management recommendations.

C5b-9 Glomerular Deposits Are Associated With Poor Renal Survival in Membranous Nephropathy

Membranous nephropathy (MN) is the first cause of nephrotic syndrome in patients without diabetes. Its prognosis is variable, and treatment remains controversial because of potential toxicity. Currently, there is no reliable prognostic marker common to all etiologies of MN and routinely available to predict the disease course and guide therapeutic management. Despite the major role of complement in the glomerular damage of MN, its prognostic impact has never been studied. We investigated the frequency and prognostic impact of glomerular deposition of C5b-9 in MN. We retrospectively selected adults diagnosed with MN (primary or secondary) at Montpellier University Hospital between December 2004 and December 2015. To be included, all patients were required to have complete medical data and a kidney tissue sample for further immunohistochemistry. We performed PLA2R1, C4d, and C5b-9 staining by immunohistochemistry. Sixty-four adults were included: 45 with primary MN and 19 with secondary MN. C4d was positive in the glomeruli of 61 adults (95.3%). Twenty-nine adults (45.3%) had glomerular deposition of C5b-9. Patients with glomerular deposition of C5b-9 had more severe nephrotic syndrome on diagnosis and lower remission and renal survival rates than adults without. C5b-9 glomerular staining is a powerful and easily accessible tool for stratifying adults according to their renal prognosis. The efficacy of complement inhibitors should be tested in adults with glomerular deposition of C5b-9.

Comparison of Lipid Profile in Different Types of Steroid Sensitive Idiopathic Relapsing Nephrotic Syndrome in Children during Active Disease and Remission

Introduction: Nephrotic syndrome is a disease of relapse and remission. Relapse rate is more than 80%. Hyperlipidemia and hypoalbuminemia are important characteristic of nephrotic syndrome. Hyperlipidemia persist even after remission of disease in frequent relapse nephrotic syndrome possibly due to frequent attack of disease and frequent use of steroid. Hyperlipidemia causes premature atherosclerosis, progressive renal injury leading to chronic renal failure, cardiac complications (myocardial infarction, hypertension), cerebrovascular disease and frequent relapse of nephrotic syndrome. Objectives: The aim of study was to see the lipid profile and comparison of lipid profile among different types of steroid sensitive idiopathic relapsing nephrotic syndrome during active disease and in remission. Materials and Methods: A cross sectional study included 120 ( 40 in each group) children aged 2-16 years with steroid sensitive idiopathic relapsing nephrotic syndrome patients who were admitted or attended in out patients department (OPD) in paediatric nephrology department Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh, during December 2014 to December 2015. They were clinically examined and fasting lipid profile was done in each case during active disease and after one month of urinary remission. The study population were divided into three groups- Infrequent relapse nephrotic syndrome (IFRNS), frequent relapse nephrotic syndrome ( FRNS ) and steroid dependent nephrotic syndrome (SDNS) based on clinical response. Results: Total patients were 120 (40 in each group). The study showed a male predominance with a male to female ratio 2.24:1, male patients were 69%, female 31%. In all cases, there were increased mean total cholesterol, low density lipoprotein ( LDL ) , triglyceride (TG) and high density lipoprotein (HDL) was normal during active disease, more raised in FRNS and SDNS.There was significant decrease in the mean level of total cholesterol, LDL and triglyceride during remission ( p &lt;0.001). Cholesterol became normal but triglyceride and LDL remained elevated even after one month of urinary remission in FRNS and SDNS. Conclusion: Hyperlipidemia persist during remission of steroid sensitive relapsing nephrotic syndrome. Children with FRNS and SDNS should be addressed with lipid lowering medication, healthy foods and healthy life style. Multicenter prospective studies with larger sample are needed for validating the findings of the present study. Medicine Today 2022 Vol.34(2): 111-116

Ruxolitinib-loaded black phosphorus nanosheets actively target proximal tubule cells to ameliorate nephrotic syndrome by reducing inflammation and oxidative stress

Nephrotic syndrome (NS) is one of the most common pediatric kidney diseases characterized by massive proteinuria and generalized edema that accounts for considerable mortality. Although the etiology of NS is not yet fully understood, altered mitochondrial metabolism, higher levels of oxidative stress, and chronic inflammation are considered the main causes of NS. Thus, reducing the level of reactive oxygen species (ROS) and inhibiting inflammation may effectively improve NS. In this study, the small molecule compound ruxolitinib phosphate salt (RP) was identified and we found it could improve NS by inhibiting cellular inflammation and reducing ROS production to exert a cytoprotective effect, but it also had some side effects. A novel two-dimensional material, black phosphorus nanosheets (BPNSs), was used to efficiently load RP and proximal tubule cells (PTCs) targeting peptide G3-C12 through electrostatic interaction. The modification of G3-C12 promoted cellular uptake of BPNSs, and the endocytosis of BPNSs@G3-C12 was primarily via micropinocytosis. RP@BPNSs@G3-C12 actively targeted PTCs and released RP in a pH-responsive manner in the acidic microenvironment of inflammation. It inhibited LPS-triggered activation of the NF-κB and JNK signaling pathways in RAW264.7 cells, and reduced the production of inflammatory factors such as NO, TNF-α, and IL-6. RP@BPNSs@G3-C12 further exhibited cytoprotective effect against doxorubicin damage, oxidative stress and apoptosis. The anti-apoptotic effect may be mainly through the Caspase 3 signaling pathway. Moreover, RP@BPNSs@G3-C12 treatment could also reduce renal inflammation, improve renal injury, apoptosis and oxidative stress in vivo, thereby improve renal functions of NS patients.

Cholinesterase is a Potential Biomarker with High Accuracy for the Nephrotic Syndrome Diagnosis in Minors.

BackgroundSerum Cholinesterase (CHE) levels have been found to be elevated in individuals with nephrotic syndrome (NS); nevertheless, it is unknown whether CHE can serve as a biomarker for NS diagnosis and what its diagnostic relevance is for NS in minors.MethodsIn this study, 138 minors aged 1–17 years with NS were enrolled, including 101 patients with the first episode of NS and 37 patients with relapsing NS. One hundred and four minors suffering from nephritis and 109 healthy minors were included as control groups. The clinical information and laboratory data of all NS patients and the control group were obtained. Logistic regression, correlation analyses and receiver operator characteristic curve were used to examine the value of CHE for NS patients.ResultsCompared to patients diagnosed with nephritis and healthy minors in the control group, the serum CHE levels of total/first episode/relapsing NS patients were substantially higher (P < 0.05). The CHE was an independent risk predictor of total (adjusted odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.57–3.18)/first episode (adjusted OR = 4.02, 95% CI: 1.47–11.08)/relapsing (adjusted OR = 2.04, 95% CI: 1.42–2.93) NS, and was positively correlated with total cholesterol in total/first episode/relapsing NS patients, respectively. The optimal cutoff for total/first episode/relapsing NS all was 11 KU/L, but the diagnostic accuracy in first episode NS (area under the curve [AUC] = 0.96, 95% CI: 0.94–0.98) was higher than the total NS (AUC = 0.93, 95% CI: 0.91–0.96) and relapsing NS (AUC = 0.85, 95% CI: 0.78–0.92).ConclusionCHE is a possible biomarker for NS and has good diagnostic accuracy for NS in minors, particularly for the first episode of NS in minors.

Clinical Significance of Urine Podocyte Messenger Ribonucleic Acids in Idiopathic Nephrotic Syndrome and Lupus Nephritis Patients

Clinical Significance of Urine Podocyte Messenger Ribonucleic Acids in Idiopathic Nephrotic Syndrome and Lupus Nephritis Patients

Subclinical hypothyroidism in children with idiopathic childhood nephrotic syndrome at a tertiary institution in South-West Nigeria.

Hypothyroidism in children with nephrotic syndrome (NS) is often attributed to prolonged loss of thyroxine binding globulin and thyroid hormones alongside protein in the urine. It has been historically associated with steroid-resistant NS alone. However, recent evidence supports the fact that subclinical hypothyroidism (SCH) does occur even in children with steroid responsive NS. Complications such as weight gain, hypercholesterolemia, delayed growth, delayed puberty, and depression could result from hypothyroidism and be erroneously attributed to NS, or the effect of steroid used in treatment. Incidentally salt intake, the major form of dietary iodine is often restricted in children with NS, possibly exacerbating any underlying hypothyroid state. The study aimed to determine the burden of SCH among our cohort of NS patients. A comparative cross-sectional study was designed to assess SCH [defined by high TSH (>6.0 mU/L and normal free T4 (0.8-2.0 ng/dl)] in hundred children with NS aged between one and fifteen years compared with hundred age and gender matched comparison group without NS. Blood and urine samples were collected to analyze thyroid function, serum albumin, serum protein and urinary protein. The prevalence of SCH was significantly higher in subjects with NS than their age, sex matched comparison group (12% vs. 2%, P = 0.006). The highest proportion (24.1%) of the children with NS who had SCH was found in the age range of 11-15 years and majority were females (19.4% vs. 7.8%, respectively, P = 0.086). The proportion of children with SCH were higher in those with steroid-resistant NS than those responsive to steroids (26.3% vs. 8.6% P = 0.033). The average values of serum albumin and protein were also significantly lower in children with SCH than those without (2.91 mg/dl ± 0.8 vs. 3.78 mg/dl ± 0.9 and 3.99 mg/dl ± 1.3 vs. 5.02 mg/dl ± 1.3, respectively, P < 0.005). Also, the average value of urinary protein was significantly higher in those with SCH than those without [94.29 mg/dl (42.3-101.0) vs. 69.19 mg/dL (31.2-108.2), respectively, P = 0.023]. Participants with steroid-resistant NS have almost three-folds odd of developing SCH compared to steroid sensitive subjects (AOR 2.901; 95% CI 1.831-4.012; P = 0.038). Screening of children for SCH with NS especially steroid-resistant NS and frequent relapsing steroid sensitive NS for hypothyroidism before complications arise is pertinent to their holistic management. This becomes even more imperative in our environment as iodine deficiency hypothyroidism is still prevalent in some parts of the country.

Childhood nephrotic syndrome and the clinical profile of thromboembolism: a systematic review and meta-analysis.

Nephrotic syndrome (NS) is a common kidney disease of childhood, affecting 2-7 children per 100,000. A potentially life-threatening complication affecting children with NS is thromboembolism (TE). However, there remains a paucity of information regarding the burden of TE and its associated risk factors in this population. A systematic review was performed on observational studies examining TE events in children with NS, published in Medline, Embase, CINAHL, and CENTRAL, until May 2021. Meta-analyses were separately conducted on the prevalence of TE within articles exclusively studying children with congenital NS and among articles including all forms of NS. Out of 13,626 articles, 22 were included (14,290 children). The pooled prevalence of symptomatic TE among articles including patients with all forms of NS was 3.60% (95% CI 1.95-5.63), which increased to 8.70% (95% CI 5.11-12.96) in articles with exclusively congenital NS patients. Children with steroid-resistant NS were at a higher risk of TE compared to steroid-sensitive children (OR 4.40, 95% CI 1.34-15.59, p = 0.013). Focal segmental glomerulosclerosis was the most common histology present in patients with TE (51.2%). Children diagnosed with NS have a significant risk of TE, particularly in patients with congenital NS and steroid resistance. IMPACT: The prevalence of symptomatic thromboembolic (TE) events in children with nephrotic syndrome (NS) was 3.60% (95% CI 1.95-5.63), which increased more than two-fold in children with congenital NS to 8.70% (95% CI 5.11-12.96). Potential risk factors for TE events in this population include congenital forms of NS and steroid resistance. This review provides a better estimate of the prevalence of TE in children with NS, while identifying potentially higher-risk populations who may benefit from TE screening and thromboprophylaxis.

Non-Diabetic Nephrotic Syndrome in Patients with Diabetes Mellitus

Abstract Type 2 diabetic nephropathy may be the consequence of some non-diabetic form of renal disease, unlike type 1 diabetes mellitus (DM) of long duration (≥10 years) in which severe proteinuria is always related to a well -defined pattern of diabetic nephropathy. The clinical manifestations of diabetic nephropathy are similar in type 1 and type 2 diabetes, while the renal lesions may differ. Diabetic glomerulopathy is the predominant renal lesion in type 1 diabetes, although tubular, interstitial and arteriolar lesions are also present in the advanced stages of renal disease. In contrast, in type 2 diabetes renal lesions are heterogeneous and several patients who fall into this category and who also suffer from diabetic kidney disease have mild or absent glomerulopathy with tubulointerstitial and/or arteriolar abnormalities. In addition, a high prevalence of non-diabetic renal diseases (NDRD), isolated or superimposed on classic diabetic nephropathy lesions have been reported in patients with type 2 diabetes, often reflecting the bias of selecting patients for unusual clinical presentations for renal biopsy. In this case report is illustrated that the nephrotic syndrome in patients with diabetes mellitus is not always associated with diabetic nephropathy non-diabetic renal disease.