Diagnosis Of Minimal Change Disease Research Articles

Immunoglobulin G4-related disease presenting with nephrotic syndrome due to minimal change disease: a case report

BackgroundImmunoglobulin G4-related disease is an inflammatory disease affecting multiple organs including the kidney. Immunoglobulin G4-related kidney disease most commonly manifests as a tubulointerstitial nephritis and is associated with glomerular disease in a proportion of cases. Membranous nephropathy is the most frequent glomerular lesion. Herein, we report the first documented case of immunoglobulin G4-related disease presenting with nephrotic syndrome owing to minimal change disease.Case presentationA 67-year-old South Asian male presented to our service with systemic upset and leg swelling. He had heavy proteinuria (urine protein:creatinine ratio 1042 mg/mmol) and was hypoalbuminemic (17 g/L) and hypercholersterolemic (9.3 mmol/L), consistent with the nephrotic syndrome. His serum creatinine was 140 μmol/L, and he was hypocomplementemic (C3 0.59 g/L, C4 < 0.02 g/L) with raised immunoglobulin G4 subclass levels (5.29 g/L). Kidney biopsy demonstrated minimal change disease alongside a plasma-cell-rich tubulointerstitial nephritis with strong positive staining for immunoglobulin G4. A diagnosis of minimal change disease in the setting of immunoglobulin G4-related disease was made. He was commenced on oral prednisolone at 60 mg daily but suffered infectious complications, including necrotizing fasciitis within 3 weeks of starting treatment, ultimately resulting in his death 52 days after initial presentation.ConclusionThis case highlights the potential for immunoglobulin G4-related disease to be associated with a spectrum of glomerular pathologies including minimal change disease. It adds to the differential diagnosis of secondary causes of minimal change disease, and moreover, aids as an important reminder of the potential complications of high-dose steroids used in its treatment.

Development and validation of a simple-to-use nomogram for predicting minimal change disease based on quantification of color Doppler sonography data from a region of interest.

To establish a simple-to-use nomogram based on quantification of color Doppler sonography data from a region of interest (ROI) to diagnose minimal change disease (MCD) promptly and non-invasively, and to evaluate the prediction capability of the nomogram. We recruited 564 patients with pathology-proven renal disease who were admitted to our hospital from July 2020 to July 2021 (388 patients in the training dataset and 176 patients in the validation dataset), and their color Doppler sonography data were acquired from a ROI and underwent ipsilateral renal biopsy. The collected clinical features and ultrasonic features were imported into Rstuido and statistically significant features were selected by stepwise regression using the forward-backward method. Multivariate Logistic regression analysis was combined with clinical analysis to obtain the final modeling features. General and dynamic nomogram models were constructed with the selected features, depending on whether they were MCD or not. Bootstrapping and internal validation were used for internal and external validation of the nomogram, respectively. The performance of the nomogram was assessed by C-index, calibration curve, and receiver operating characteristic (ROC) curve. Age and VI were independent factors in predicting MCD. The value of Age (Best cut-off value: 33.5years) combined with VI (Best cut-off value: 40.50 points) in the diagnosis of MCD was significantly higher than that of single diagnosis (AUC 0.901, 95% CI 0.863-0.938). The C-index of the nomogram constructed with age and VI in the training and validation datasets was 0.915 [95% confidence interval (CI) 0.874-0.956 and 0.875 95% CI 0.783-0.967], respectively. Calibration curves were fitted well. The sensitivity, specificity, and accuracy were 76.1%, 95.6%, and 78.3%, respectively, in the training dataset, and 74.1%, 94.4%, and 76.1% in the validation dataset, respectively. The nomogram constructed with age and VI showed a satisfactory degree of differentiation and accuracy, which is of great significance for early, non-invasively, and individually analysis of the risk of MCD.

Urinary CD80 and Serum suPAR as Biomarkers of Glomerular Disease among Adults in Brazil.

Urinary CD80 has been shown to have good specificity for minimal change disease (MCD) in children. However, the investigation of circulating factors such as soluble urokinase plasminogen activator receptor (suPAR) as biomarkers of focal segmental glomerulosclerosis (FSGS) is quite controversial. The objective of this study was to determine whether urinary CD80 and serum suPAR can be used for the diagnosis of MCD and FSGS, respectively, in the adult population of Brazil. We also attempted to determine whether those biomarkers assess the response to immunosuppressive treatment. This was a prospective study in which urine and blood samples were collected for analysis of CD80 and suPAR, respectively, only in the moment of renal biopsy, from patients undergoing to diagnostic renal biopsy. At and six months after biopsy, we analyzed serum creatinine, serum albumin, and proteinuria in order to evaluate the use of the CD80 and suPAR collected in diagnosis as markers of response to immunosuppressive treatment. In healthy controls were collected urinary CD80 and proteinuria, serum suPAR, and creatinine. The results of 70 renal biopsies were grouped, by diagnosis, as follows: FSGS (n = 18); membranous nephropathy (n = 14); MCD (n = 5); and other glomerulopathies (n = 33). There was no significant difference among the groups in terms of the urinary CD80 levels, and serum suPAR was not significantly higher in the FSGS group, as would have been expected. Urinary CD80 correlated positively with nephrotic syndrome, regardless of the type of glomerular disease. Neither biomarker correlated with proteinuria at six months after biopsy. In adults, urinary CD80 can serve as a marker of nephrotic syndrome but is not specific for MCD, whereas serum suPAR does not appear to be useful as a diagnostic or treatment response marker.

Potential Urine Proteomic Biomarkers for Focal Segmental Glomerulosclerosis and Minimal Change Disease.

Primary focal segmental glomerulosclerosis (FSGS), along with minimal change disease (MCD), are diseases with primary podocyte damage that are clinically manifested by the nephrotic syndrome. The pathogenesis of these podocytopathies is still unknown, and therefore, the search for biomarkers of these diseases is ongoing. Our aim was to determine of the proteomic profile of urine from patients with FSGS and MCD. Patients with a confirmed diagnosis of FSGS (n = 30) and MCD (n = 9) were recruited for the study. For a comprehensive assessment of the severity of FSGS a special index was introduced, which was calculated as follows: the first score was assigned depending on the level of eGFR, the second score—depending on the proteinuria level, the third score—resistance to steroid therapy. Patients with the sum of these scores of less than 3 were included in group 1, with 3 or more—in group 2. The urinary proteome was analyzed using liquid chromatography/mass spectrometry. The proteome profiles of patients with severe progressive FSGS from group 2, mild FSGS from group 1 and MCD were compared. Results of the label free analysis were validated using targeted LC-MS based on multiple reaction monitoring (MRM) with stable isotope labelled peptide standards (SIS) available for 47 of the 76 proteins identified as differentiating between at least one pair of groups. Quantitative MRM SIS validation measurements for these 47 proteins revealed 22 proteins with significant differences between at least one of the two group pairs and 14 proteins were validated for both comparisons. In addition, all of the 22 proteins validated by MRM SIS analysis showed the same direction of change as at the discovery stage with label-free LC-MS analysis, i.e., up or down regulation in MCD and FSGS1 against FSGS2. Patients from the FSGS group 2 showed a significantly different profile from both FSGS group 1 and MCD. Among the 47 significantly differentiating proteins, the most significant were apolipoprotein A-IV, hemopexin, vitronectin, gelsolin, components of the complement system (C4b, factors B and I), retinol- and vitamin D-binding proteins. Patients with mild form of FSGS and MCD showed lower levels of Cystatin C, gelsolin and complement factor I.

Nephrotic syndrome of minimal change disease following exposure to mercury-containing skin lightening cream: A case report and literature review

Long-term exposure to mercury-containing skin lightening cream can cause mercury-related nephropathy, among which, membranous nephropathy (MN) and minimal change disease (MCD) are the main pathological types. In contrast to these two conditions, MCD with IgA deposition is not a common disease. In the present study, we report a 65-year-old Asian woman who developed nephrotic syndrome following long-term use of mercury-containing skin lightening cream. The urine mercury level of the patient was significantly increased, and the results of the renal biopsy indicated diagnosis of MCD with IgA deposition. Following three courses of treatment with sodium dimercaptopropane sulfonate (DMPS) alone and discontinuation of the skin cream, the symptoms of the patient were relieved without use of glucocorticoids, with proteinuria turning negative and a significant reduction in urine mercury levels. During the 6-month follow-up period, routine urinalysis remained normal. By reviewing relevant published literature, we summarized the pathological characteristics, possible mechanism of action, and treatment strategies of mercury poisoning-related MCD. The possibility of mercury poisoning should be considered for patients with nephropathy and history of use of skin lightening cosmetics. In these patients, the urine mercury levels should be measured in time so that mercury removal therapy can be implemented early.

Spontaneous remission of idiopathic minimal change disease in a cat

A 5-year-old female neutered domestic mediumhair cat presented with acute onset hyporexia, lethargy, ascites, hypoalbuminaemia and ventral subcutaneous oedema. Further investigations revealed a bicavitary effusion, myocardial injury, hypercholesterolaemia and concurrent marked proteinuria. A panel of infectious disease tests yielded negative results. Nephrotic syndrome was suspected and renal biopsies were performed. Histopathology and electron microscopy confirmed a diagnosis of minimal change disease (MCD). The patient was successfully managed with benazepril, clopidogrel and a veterinary prescription renal diet. Follow-up two weeks later documented almost complete resolution of the cardiac abnormalities, absence of clinical signs and marked improvement in clinicopathological findings. The hypoalbuminaemia and proteinuria had resolved two months after presentation. At the time of writing, 13 months post-admission, the cat remained asymptomatic with no evidence of disease relapse. MCD is rarely described in the veterinary literature, with only four cases reported to date. To our knowledge, this report describes the first case of successfully treated MCD-associated nephrotic syndrome in a cat without the use of glucocorticoid treatment.

MO219: Are C4D, Nephrın and WT1 Expressıons İmportant ın the Dıfferentıal Dıagnosıs between Focal Segmental Glomerulosclerosıs and Mınımal Change Dısease?

Abstract BACKGROUND AND AIMS Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) are most common seen glomerulonephritis. Differential diagnosis between FSGS and MCD by light microscopy (LM) cannot be made in some times. In this situation, electron microscopy (EM) is needed for differential diagnosis. Rarely, EM may not be sufficient for differential diagnosis. There are needed new markers for differential diagnose between FSGS and MCD. The aim of this study is to determine which of the glomerular C4d, nephrine staining is specific and sensitive for FSGS and MCD. C4d, Recent experimental data show that complement activation plays a pathogenic role in the development of FSGS. Therefore, C4d staining in the sclerotic focus of the glomeruli in FSGS patients may have an important differential diagnosis. Nephrine is the main component of the slit diaphragm that connects the foot protrusions of the podocytes. Epithelial cell and podocyte dysfunction occurs as a result of defects in the genes encoding these key proteins expressed in GBM. Wilms’ tumour suppressor gene (WT1) is a transcription factor that plays very important role in the embryonal development of the genital organs and kidney. WT-1 is expressed in podocytes and is an important transcription factor for podocyte function. METHOD This is a retrospective study, comprised of patients diagnosed as FSGS, MCD and the ones who diagnosed as having FSGS or MCD couldnot be differentiated. The patients were divided into three groups. Group 1: FSGS patients, Group 2: patients with indefinite diagnosis; either FSGS or MCD and Group 3: MCD patients. All biopsy materials were stained with C4d, WT1 and nephrine. The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of C4d, WT1 and nephrine were evaluated for the diagnosis of both FSGS and MCD. RESULTS C4d staining in group 1 was significantly higher compared with group 2 and group 3 (P &amp;lt; .05). Nephrine was shown significantly more staining in group 3 patients than group 1 (P &amp;lt; .05). C4d was found to be associated with the presence of global or segmental sclerosis in the glomeruli, adhesion to the Bowman's capsule (P &amp;lt; .05). The specificity and sensitivity of C4d in FSGS patients were 85%, 73.9%, while it was 26.1% and 15.4% in MCD. Specificity and sensitivity of nephrine were 87%, 69% in MCD patients compared with 30.8% and 13% in FSGS (Fig. 1). PPV and NPV values of C4d and nephrine in FSGS and MCD were shown in Figure 2. CONCLUSION C4d and nephrine have predictive diagnostic value for FSGS and MCD respectively. C4d and nephrine are more specific and sensitive to FSGS and MCD, respectively. However, there is a need for randomized studies with larger study groups

Potential relationship between eGFRcystatin C /eGFRcreatinine -ratio and glomerular basement membrane thickness in diabetic kidney disease.

Diabetic kidney disease (DKD) is a leading cause of end‐stage renal disease and renal replacement therapy worldwide. A pathophysiological hallmark of DKD is glomerular basal membrane (GBM) thickening, whereas this feature is absent in minimal change disease (MCD). According to fundamental transport physiological principles, a thicker GBM will impede the diffusion of middle‐molecules such as cystatin C, potentially leading to a lower estimated GFR (eGFR) from cystatin C compared to that of creatinine. Here we test the hypothesis that thickening of the glomerular filter leads to an increased diffusion length, and lower clearance, of cystatin C. Twenty‐nine patients with a kidney biopsy diagnosis of either DKD (n = 17) or MCD (n = 12) were retrospectively included in the study. GBM thickness was measured at 20 separate locations in the biopsy specimen and plasma levels of cystatin C and creatinine were retrieved from health records. A modified two‐pore model was used to simulate the effects of a thicker GBM on glomerular water and solute transport. The mean age of the patients was 52 years, and 38% were women. The mean eGFRcystatin C/eGFRcreatinine‐ratio was 74% in DKD compared to 98% in MCD (p < 0.001). Average GBM thickness was strongly inversely correlated to the eGFRcystatin C/eGFRcreatinine‐ratio (Pearson's r = −0.61, p < 0.01). Two‐pore modeling predicted a eGFRcystatin C/eGFRcreatinine‐ratio of 78% in DKD. We provide clinical and theoretical evidence suggesting that thickening of the glomerular filter, increasing the diffusion length of cystatin C, lowers the eGFRcystatin C/eGFRcreatinine‐ratio in DKD.

Association between diuretic administration before diagnosis and incidence of acute kidney injury in patients with minimal change disease: A single-center observational study.

We examined the association between diuretic administration before the diagnosis of minimal change disease and the incidence of acute kidney injury. Moreover, we examined whether the use of diuretics affected the time to complete remission in adults with such disease.The present study was a single-center, retrospective, observational cohort study. We included 107 patients with biopsy-proven minimal change disease who were treated at a tertiary referral center in Japan between January 1, 2000 and March 31, 2019. All biopsy specimens were examined by a board-certified renal pathologist. The patients were considered to have minimal change disease when the kidney biopsy specimen had no glomerular lesions or only mild focal mesangial prominence (not exceeding 3 or 4 cells per segment) by light microscopy and/or foot process effacement by electron microscopy. Logistic regression and Kaplan–Meier curve analyses were performed, comparing the data of patients who received diuretics or not.The median age was 47 (28–66) years, 52% of patients were women, and the median proteinuria dosage was 8.3 (5.3–11.2) g/d. When minimal change disease was diagnosed, 27% of patients were taking diuretics. Within 30 days after the diagnosis, acute kidney injury occurred in 27% of patients. On multivariable logistic regression analysis, the use of diuretics was significantly associated with a higher risk of acute kidney injury. The use of diuretics was also associated with a longer time to complete remission.Diuretic administration can be associated with an elevated acute kidney injury risk and longer remission time in adult patients with newly diagnosed minimal change disease.

Therapeutic Response to Corticosteroids Remains a Valid Approach to Initial Management of Children With Idiopathic Nephrotic Syndrome.

Complete remission of idiopathic nephrotic syndrome (INS) in response to corticosteroids has been widely adopted as an indicator of satisfactory long-term outcomes in pediatric patients. The approach was based on the results of studies conducted in the 1960s and 1970s. The studies found that corticosteroid-responsive minimal change disease (MCD) was the most frequent diagnosis in INS patients. In more recent years, studies have reported increased frequency of focal segmental glomerulosclerosis (FSGS) and primary corticosteroid resistance without a corresponding increase of FSGS. It became unclear whether withholding kidney biopsy before treatment with corticosteroids is still the best management practice. We performed a retrospective chart review at the UPMC Children's Hospital of Pittsburgh and identified patients who were referred for evaluation of edema or proteinuria between 2002 and 2014. We identified 114 pediatric patients with INS who were treated initially with a corticosteroid (prednisone or prednisolone) 2 mg/kg (max 60 mg)/day for 4–6 weeks followed by 2 mg/kg (max 60 mg) every other day for 4–6 weeks and had not received a corticosteroid-sparing agent before completing at least 8 weeks of the initial therapy. Corticosteroid resistance in pediatric INS patients was independently associated with the black race, older age at presentation (>8 years), and female sex. The majority of blacks who were resistant to corticosteroids had a tissue diagnosis of MCD. Among the whites who were steroid-resistant, MCD and FSGS were diagnosed in similar proportions of cases. Thus, the tissue diagnosis in could not predict the response to corticosteroids. Nineteen percent of whites with FSGS were steroid-sensitive and none of the blacks with FSGS responded to corticosteroids. These data suggest that the histologic diagnosis of FSGS could not rule out response to corticosteroids, at least, in the white patient population. In summary, our data demonstrate that at this time, the therapeutic response to corticosteroids continues to be a valid approach for the initial evaluation and therapy of children diagnosed with INS at our center. Future studies should evaluate the mechanisms of changing characteristics of pediatric INS. The specific role of patient demographics, ethnicity, as well as genetic and environmental factors could be evaluated by a prospective, multicenter study.

Electron microscopy situation in the diagnosis of minimal change disease; a 16-year survey

Introduction: Minimal change disease (MCD) is one of the most common diseases affecting glomeruli and causing nephrotic syndrome in both adults and children. Objectives: The aim of this study was to evaluate the degree of accordance between light, fluorescent, and electron microscopies in the diagnosis of MCD. Patients and Methods: In this cross-sectional study, we investigated kidney biopsies which were sent to the referral electron microscopy unit (affiliated to Shiraz University of Medical Sciences) from 2001 to 2016. The final diagnosis of MCD was based on the electron microscopy (EM) study. For each patient, the primary light microscopy (LM) finding was compared with EM diagnosis. The available patients’ demographic, clinical, and paraclinical data were extracted. All the statistical analysis was performed in SPSS 19.0 and P&lt;0.05 was considered as statistically significant. Results: Among all 2865 kidney biopsies, the data of 143 (5.0%) patients with approved MCD by EM were analyzed. The mean age of patients was 23.1± 17.4 years since most of them were male (54.9%). Normal blood urea nitrogen (BUN) and creatinine were observed in 76.6% and 78.6% of them respectively. Around, 140 (97.9%) of patients had no tubular atrophy and interstitial fibrosis. The role of EM in the diagnosis of MCD for 61 (50.0%) of cases were essential, for 61 (50.0%) cases were helpful while there was no case with the role of non-necessary. The immunofluorescence (IF) study was performed for 99 (69.2%) patients. Among them, it was negative for 60 (60.6%) of cases and was positive for IgM and C3 in 19 (19.2%) and 11 (11.1%) of cases respectively. The proportion of flank pain was significantly higher among adults. Conclusion: The importance of EM for the diagnosis of MCD is indispensable and undeniable; while LM is not capable of independently leading to a certain diagnosis of MCD. Considering the limitations of using EM, the results obtained from this study can help with the appropriate use of electron microscopy and help physicians to reach earlier diagnosed.

Immunoglobulin G/albumin staining in tubular protein reabsorption droplets in minimal change disease and focal segmental glomerulosclerosis.

Some renal biopsies cannot distinguish minimal change disease (MCD) from primary focal segmental glomerulosclerosis (FSGS) because of inadequate sampling and/or a lack of sampled glomeruli with segmental sclerosis. As protein excretion in MCD has been described as being albumin-selective, we examined whether the ratio of immunoglobulin G (IgG)/albumin staining in protein reabsorption droplets (tPRD) might help distinguish MCD from FSGS. Frozen tissue from 144 native renal biopsies from patients with nephrotic syndrome and a diagnosis of MCD or FSGS [73 MCD, 30 FSGS tip variant (FSGS-tip), 38 FSGS-not otherwise specified (FSGS-NOS), 3 FSGS collapsing] was retrospectively stained by direct immunofluorescence for IgG and albumin; none of these samples showed diagnostic lesions of FSGS. IgG and albumin staining of tPRD were graded on a scale of 0 to 3+ based on the distribution and intensity of staining. Mean (standard deviation) IgG/albumin staining ratios were 0.186 ± 0.239 for MCD, 0.423 ± 0.334 for FSGS-tip (P = 0.0001 versus MCD) and 0.693 ± 0.297 for FSGS-NOS (P < 0.0001 versus MCD; P = 0.0001 versus FSGS-tip). Of 84 biopsies with a ratio ≤0.33, 63 (75%) showed MCD, whereas among 21 with a ratio of 1.0, all but one showed FSGS (15 FSGS-NOS). In summary, IgG/albumin staining in tPRD was correlated with histologic diagnosis in renal biopsies with MCD and FSGS. A ratio of ≤0.33 was associated with MCD, whereas a ratio of 1.0 was most often seen with FSGS-NOS.

Podocin and uPAR are good biomarkers in cases of Focal and segmental glomerulosclerosis in pediatric renal biopsies.

There are controversies whether Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are distinct glomerular lesions or different manifestations within the same spectrum of diseases. The uPAR (urokinase-type plasminogen activator receptor) and some slit diaphragm proteins may be altered in FSGS glomeruli and may function as biomarkers of the disease in renal biopsies. Thus, this study aims to evaluate the diagnostic potential of uPAR and glomerular proteins for differentiation between MCD and FSGS in renal pediatric biopsy. Renal biopsies from 50 children between 2 and 18 years old were selected, with diagnosis of MCD (n = 29) and FSGS (n = 21). Control group consisted of pediatric autopsies (n = 15) from patients younger than 18 years old, with no evidences of renal dysfunction. In situ expressions of WT1, nephrin, podocin and uPAR were evaluated by immunoperoxidase technique. Renal biopsy of patients with MCD and FSGS expressed fewer WT1 (p≤0.0001, F = 19.35) and nephrin (p<0.0001; H = 21.54) than patients in the control group. FSGS patients expressed fewer podocin than control (p<0.0359, H = 6.655). FSGS cases expressed more uPAR than each of control and MCD (p = 0.0019; H = 12.57) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502) in these cases. Podocin had sensitivity of 73.3% and specificity of 86.7% (p = 0.0068) and uPAR had sensitivity of 78.9% and specificity of 73.3% (p = 0.0040) for diagnosis of FSGS patients. The main limitation of the study is the limited number of cases due to the difficulty in performing biopsy in pediatric patients. Podocin and uPAR are good markers for FSGS and differentiate these cases from MCD, reinforcing the theory of distinct glomerular diseases. These findings suggest that podocin and uPAR can be used as biomarkers in the routine analysis of renal biopsies in cases of podocytopathies when the lesion (sclerosis) is not sampled.

Review of Glomerular Diseases: Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD)

Purpose: Idiopathic focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are chronic glomerulopathies which may compromise patients’ quality of life, and for which there is no cure. This literature review aimed to summarize our current understanding of the pathophysiology, clinical characteristics, and best available treatment for the two conditions in order to outline a consolidated treatment protocol and identify future research considerations.&#x0D; Methods: PubMed was systematically searched by a single reviewer in order to identify primary studies pertaining to the diagnosis, treatment and classification of FSGS and MCD. Additionally, a hand search of UpToDate was conducted to glean further information about the best available evidence as summarized for clinician use. Relevant information was extracted and synthesized.&#x0D; Results: Primary FSGS and MCD result from distinct pathogenic mechanisms, hypothesized to involve kidney injury via immune dysregulation. Patients require a kidney biopsy for diagnostic purposes. First-line treatment involves glucocorticoids (i.e. prednisone), although patients’ responsiveness may be inconsistent; second-line treatment is immunotherapy.&#x0D; Conclusion: This review summarized clinically-important information about FSGS and MCD, and emphasized the need for further research in the field of clinical nephrology. Large scale trials such as the Cure Glomerulonephropathy should be conducted to gather information about the affected population.

Immunoglobulin E and G Levels in Predicting Minimal Change Disease before Renal Biopsy.

Purpose The diagnosis of minimal change disease in adults relies mainly on renal biopsy, but this procedure is not without complications. Despite the advancements in technique of percutaneous renal biopsy, biopsy-related complications still occur. Bleeding is one of the major complications, which may lead to hemodynamic instability and, sometimes, even death. Thus, we developed a model to predict MCD for high-risk patients unsuitable for renal biopsy. Methods We enrolled 142 patients with nephrotic syndrome who received renal biopsy between October 2007 and April 2011 at one tertiary medical center in this study. Demographic, clinical, and prebiopsy laboratory variables were retrospectively recorded and analyzed. Results The overall prevalence of MCD was 26.8%. Age, hemoglobin levels, 24-hour urine protein, immunoglobulin (Ig) G, and IgE differed significantly between the MCD and non-MCD groups. Logistic regression analysis showed a significant increase in the risk of developing MCD as the number of Ig risk factors, namely, IgG < 450 mg/dl and IgE > 110 mg/dl, increased. Having both risk factors significantly increased the chances of receiving a diagnosis of MCD (by 31.84-fold, P =.007) compared with having neither. Combining the aforementioned clinical model and the 2 Ig risk factors was the best in predicting the diagnosis of MCD, with the area under a receiver-operating characteristic curve of 0.91. Conclusions Combining clinical model and this 2 Ig risk factors provides physicians simple and valuable clinical markers to diagnose MCD.

A Case Report of Nephrotic Syndrome While Undergoing Quinine Therapy

We summarize the case of an 81-year-old Caucasian female who presented to her family physician with signs and symptoms of nephrotic syndrome following a brief exposure to quinine. Prior to that visit, she was clinically well with no chronic medical ailments and met with her family physician for annual physical assessments. She had taken 11 tablets of quinine for nocturnal leg cramps over the course of 28 days before starting to notice mild peripheral edema, which subsequently progressed, leading to a family physician review. Her initial serum albumin level was 12 g/L, and a 24-hour urine protein output was quantified at 8.14 g/day; she was diagnosed as having nephrotic syndrome. A kidney biopsy confirmed the diagnosis of minimal change disease (MCD). Quinine therapy was stopped, and she was initiated on a tapering regime of prednisone with concurrent cyclosporine therapy. Within a fortnight of starting therapy, she went into remission and her immunosuppressive medications were rapidly tapered and discontinued. This paper reports an association between the use of quinine and subsequent MCD. This case report proposes that the use of quinine has an association with, and may be causal for, the development of minimal change disease. As this is yet an unreported adverse effect, this paper seeks to increase the knowledge of the varied and numerous effects of quinine.

The impact of IgM deposits on the outcome of Nephrotic syndrome in children

BackgroundThe significance of IgM deposits in glomerular mesangium has been controversial since they were first described due to the variations in the both the definitions used and described impact on clinical outcome. The aim of our study was to evaluate the significance of the IgM deposits in the glomerular mesangium for outcomes of nephrotic syndrome (NS) in children.MethodsForty-five children with NS who underwent renal biopsy at tertiary pediatric hospital from January 1st, 2000 to December 31st, 2015 and the pathology diagnosis of minimal change disease, focal segmental glomerulosclerosis and mesangial hypercellularity (MH) were retrospectively analyzed. IgM positivity was defined as ≥1+ imunofluorescence with predominantly mesangial distribution. The patients were stratified into IgM-positive (n = 18) and IgM-negative (n = 27).ResultsAt the end of the median follow-up 4.5 years (range 0.17–13.14), the IgM-positive group was represented by 11 patients (61.1%) in remission, 3 patients (16.7%) with active disease and normal kidney function, 2 (11.1%) patients with active disease and impaired kidney function, 2 (11.1%) patients on renal replacement therapy. Accordingly, the IgM-negative group included 13 patients (48.1%) in remission, 12 (44.4%) with active disease and normal kidney function, 1 (3.7%) with active disease and impaired kidney function, 1 (3.7%) on renal replacement therapy, with no statistical significance between groups (p = 0.186).ConclusionsThis study did not reveal significant differences of the disease outcomes between IgM-positive and IgM-negative groups.

Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome.

The aims of this study were (1) to detect toll-like receptor (TLR)-3, TLR-4 and CD80 expression in peripheral blood mononuclear cells (PBMCs) and estimate urinary CD80 levels in children with idiopathic nephrotic syndrome and (2) to investigate the utility of these markers to differentiate between biopsy-proven minimal change disease (MCD) and focal segmental glomeruloscelerosis (FSGS). The study included 70 patients with idiopathic nephrotic syndrome (NS), of whom 40 had steroid-sensitive NS (SSNS; 25 with active NS, 15 in remission) and 30 had steroid-resistant NS (SRNS) patients, and 23 healthy controls. TLR-3, TLR- 4 and CD80 mRNA expression levels in PBMCs were determined and the urinary CD80 level estimated. Median TLR-3, TLR-4 and CD80 mRNA expression levels were higher in patients with active SSNS than in those with SRNS, and the latter patient group also had significantly lower expression levels than the controls. The expression levels of these markers were associated with reductions in remission. Patients with biopsy-proven MCD had higher median expression levels of these markers than those with FSGS, but the differences were not statistically significant. Median urinary CD80/creatinine values were significantly higher in patients with SSNS and SRNS than in the controls and steroid-sensitive patients in remission (p < 0.001). CD80 levels were also significantly higher in patients with MCD than in those with FSGS (p = 0.002). A cut-off level of >914.5ng/g had a sensitivity of 86.6%, specificity 71.4% and area under the curve of 0.828 (95% confidence interval 0.678-0.978, p = 0.002) for the diagnosis of MCD. Increased expressions of TLR-3, TLR-4 and CD80 mRNA and the level of urinary CD80/creatinine could be useful markers to differentiate patients of SSNS in relapse from those with SRNS. Further these markers can also distinguish biopsy proven MCD from FSGS in SRNS patients.

Re-Occurring Proteinuria in a SLE Patient: Always Lupus Nephritis?

Introduction: Renal disease, designated as lupus nephritis (LN), is one of the severe manifestations of Systemic Lupus Erythematosus (SLE). The proliferative forms require aggressive treatment with corticosteroids and cytotoxic drugs. In a substantial number of patients, renal disease relapses after treatment. Case report: In this case report, we present a 27-year old woman, who had been treated for a membranoproliferative LN in the past. Seventeen years later she presented with chest pain and nephrotic-range proteinuria and severe hypoalbuminemia. The diagnosis of pulmonary embolism was made. Renal biopsy revealed only minimal abnormalities, confined to the mesangium. There was no glomerulonephritis. Based on this finding and the nephrotic-range proteinuria, the diagnosis of minimal-change disease was made. The patient was treated with prednisolone, after which the proteinuria diminished, but did not disappear. After the addition of azathioprine, the proteinuria resolved completely. Conclusion: This case illustrates that, although the diagnosis of LN has been made in the past, this does not exclude the occurrence of renal pathology caused by other diseases than SLE. Therefore, a renal biopsy is mandatory in every SLE patient with occurrence of renal abnormality es, even when a history of LN is present.

Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.

BackgroundVariability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis.MethodsParticipating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy.ResultsWe studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients.ConclusionsWe found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.