Association of Urinary Vitamin D Binding Protein and Neutrophil Gelatinase-Associated Lipocalin with Steroid Responsiveness in Idiopathic Nephrotic Syndrome of Childhood.

Idiopathic nephrotic syndrome (NS) is one of the most common kidney diseases of childhood. In this study, we assessed urine Vitamin-D binding protein (VDBP) and neutrophil gelatinase-associated lipocalin (NGAL) levels as a predictor of steroid responsiveness in idiopathic NS. This cross-sectional study included children with steroid-resistant NS (SRNS) (n = 28), steroid-sensitive NS (SSNS) (n = 28), and healthy controls (n = 28). Urine levels of VDBP and NGAL were measured using a commercially available ELISA kit and normalized to urine creatinine (Cr). Urine microalbumin (MALB) was measured using nephelometer, and MALB/Cr was calculated. Urine Vitamin-D binding protein (uVDBP) and urine neutrophil gelatinase-associated lipocalin (uNGAL) levels were statistically significantly higher (P < 0.001) in patients with SRNS (701.12 ± 371.64 ng/mL and 28.42 ± 15.40 ng/mL, respectively) than in patients with SSNS (252.87 ± 66.34 ng/mL and 8.86 ± 5.54 ng/mL, respectively) and normal controls (34.74 ± 14.10 ng/mL and 6.79 ± 1.32 ng/mL, respectively). Estimated glomerular filtration rate shows a significant negative correlation with MALB/Cr, uVDBP, and uNGAL. However, uVDBP and uNGAL showed a much higher discriminatory ability for differentiating SRNS from MALB/Cr. uVDBP and uNGAL at the cutoff value of 303.81 and 13.1 ng/mL, respectively, yielded the optimal sensitivity (82% and 86%) and specificity (78% and 89%) to distinguish SRNS from SSNS. Urine levels of VDBP and NGAL can predict steroid responsiveness in patients with idiopathic NS.

Molecular stratification of idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (INS) describes a group of pathologies of the renal glomerulus that result in the classic triad of heavy proteinuria, oedema and hypoalbuminaemia. The disease has historically been defined by evidence of distinctive histological changes in the absence of clinical evidence of a distinct pathological driver. However, the current classification is not based on any systematic mechanistic understanding of biological processes, and therefore current treatment regimens are broad, iterative and nonspecific. Over the past 20 years delineation of the underlying biology of the target cell in INS - the glomerular podocyte - has transformed our understanding of the mechanisms that contribute to breakdown of the glomerular filtration barrier and the development of INS. It is increasingly clear that nephrotic syndrome caused by monogenic mutations is distinct from immune-driven disease, which in some cases is mediated by circulating factors that target the podocyte. The combination of systems biology and bioinformatics approaches, together with powerful laboratory models and ever-growing patient registries has potential to identify disease 'signatures' that reflect the underlying molecular mechanism of INS on an individual basis. Understanding of such processes could lead to the development of targeted therapies.

Childhood nephrotic syndrome in tropical Africa: then and now.

This descriptive and comparative review examines the changing epidemiology, treatment, renal and patient outcome of childhood nephrotic syndrome (NS) in tropical Africa (TpAfr). In the 1960s to 1980s, corticosteroid-resistant non-minimal change disease (nMCD) including quartan malaria nephropathy (QMN) was the dominant renal histopathology type. The overall incidence of NS was 0.35-1.34% of hospital admissions. Median age at onset of NS ranged between 4.0 and 12.0 years while the mean (SD) age range was 5.8 (3.8) to 10.3 (4.8) years across studies. The male: female ratio was 1.6:1.0. The overall mean (SD) incidence of idiopathic minimal change disease (MCD) [21.6 (18.6%)] compared with idiopathic nMCD [59.1 (25.7%)] demonstrates significant dominance of the latter (p = 0.0001). Post-1989, the following mean (SD) incidences of histopathological types were: MCD 20.4 (17.7%), focal segmental glomerulosclerosis 39.0 (26.3%), membranoproliferative glomerulonephritis 25.4 (16.8%), proliferative glomerulonephritis 16.7 (27.0%) and membranous nephropathy 7.4 (4.5%). While the mean (SD) proportion of steroid resistance (SR) [73.5 (19.2%)] was significantly greater than the mean complete remission (CR) [26.5 (19.2%)] during 1960-1989 (p=0.005), mean (SD) SR [27.4 (25.3%)] was significantly lower than mean (SD) CR [66.1 (28.0%)] post-1989 (p < 0.001). Unlike QMN, hepatitis B virus, HIV infection, sickle cell disease and systemic lupus erythematosus are now increasingly being associated with NS in TpAfr. Mean (SD) renal survival post-1989 was 58.3 (37.0%) while all-cause mortality was 9.8%. Children with NS now survive better than before, reflecting improved access to healthcare and transition to a clinical pattern favouring idiopathic NS and increased sensitivity to corticosteroids.

Steroid-resistant nephrotic syndrome: a persistent challenge for pediatric nephrology.

Steroid-resistant nephrotic syndrome remains a challenge to treat, but various efforts are underway to better understand the pathogenesis and improve patient outcomes. This review provides an update on the newer advances in understanding the molecular etiologies for a variety of podocyte abnormalities, potential circulating factors that may initiate and sustain the steroid-resistant state, genetic mutations, and precision medicine treatment modalities in this continuously perplexing disorder.

Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome.

OBJECTIVE: To assess the safety and clinical efficacy of leflunomide (LEF) and prednisone on refractory nephrotic syndrome (RNS). METHODS: A total of 52 patients with RNS were treated for 24 weeks between 2010 and 2014 in our hospital. In the treated group, 26 patients were treated with LEF and prednisone, and, in the control group, 26 patients were treated with cyclophosphamide (CTX) and prednisone. During the treatment, 24 h urinary protein excretion and the serum levels of albumin and cholesterol, and kidney function were assayed before and after the therapy. Adverse reactions during treatment were recorded. RESULTS: In the LEF group, the medication was markedly effective in eight cases and effective in nine cases; the total efficacy rate was 65.30%. In the CTX group, the treatment was markedly effective in six cases and effective in nine cases; the total efficacy rate was 57%. There were no significant differences between the results of the total efficacy rate (p > .05). The 24 h urinary protein excretion and serum cholesterol levels in both groups decreased after therapy and the serum levels of albumin in both groups increased after therapy. There were significant differences between the results for the 24 h urinary protein excretion, serum levels of albumin and cholesterol in the two groups (p < .05). The treatments were well tolerated in both groups. CONCLUSION: LEF combined with prednisone has a certain efficacy on the RNS and displays few adverse reactions. A large-sample, randomized double-blind controlled study and long-term follow-up are needed to verify the efficacy of LEF combined with prednisone.

Interferón ß, microangiopatía trombótica y síndrome nefrótico / Interferon ß, nephrotic syndrome and thrombotic microangiopathy

No disponible

Study of nephrotic syndrome in children: importance of light, immunoflourescence and electron microscopic observations to a correct classification of glomerulopathies.

OBJECTIVE: To evaluate the contribution of electron microscopy (EM) to the accurate diagnosis of glomerulopathies in childhood nephrotic syndrome (NS) in a developing country. METHODS: The study was carried out at the Histopathology Department, Sindh Institute of Urology and Transplantation (SIUT) from April 2007 to March 2008. All children (≤18 years) presenting with NS were included. Patients' demographic, clinical, laboratory, and biopsy data were retrieved from case records and biopsy reports. Renal biopsies were studied by light microscopy, immunoflourescence, and EM. RESULTS: The mean age of 74 children was 11.34, 4.85 years, EM was useful in 97.2% of cases, being essential in 31% and helpful in 66.2% cases. CONCLUSION: The results demonstrate that the ultrastructural study is both helpful and essential to a correct classification of glomerular diseases underlying NS in children in nearly all cases and whenever feasible this should be used in the pathologic evaluation of renal biopsies.

Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome.

BACKGROUND: Rituximab (RTX) is a promising option for treating childhood-onset steroid-dependent (SDNS), frequently relapsing (FRNS), and steroid-resistant (SRNS) nephrotic syndrome. METHODS: We retrospectively surveyed RTX treatment for these conditions to evaluate its indications, efficacy and adverse events. Questionnaires were sent to 141 hospitals in Japan. RESULTS: Seventy-four patients (52 SDNS; 3 FRNS; 19 SRNS) were treated with RTX because of resistance to various immunosuppressive agents. Most patients received a single administration of RTX (85%). Forty-one of 53 SDNS/FRNS (77%) and 5 of 17 SRNS (29%) patients successfully discontinued prednisolone (16 SDNS/FRNS and 6 SRNS achieved their first discontinuation since onset), and 17 out of 53 SDNS/FRNS patients (31%) discontinued cyclosporine. However, 28 of the 53 patients (51%) relapsed. Although immunosuppressive agents did not extend B cell depletion, relapses were significantly less if immunosuppressive agents were continued after RTX (P = 0.006; hazard ratio = 0.2). Among the SRNS patients, complete (n = 6) and partial remission (n = 6) were achieved. No life-threatening adverse events were experienced. CONCLUSIONS: Although this was a multi-center survey where treatment of nephrotic syndrome varied between centers, the steroid-sparing effect of RTX in SDNS/FRNS was excellent. If single administration of RTX is chosen, continuation of immunosuppressive agents is recommended for prevention of relapse.

Severity of nephrotic IgA nephropathy according to the Oxford classification.

BACKGROUND: IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused. METHODS: In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy. RESULTS: In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1 ± 24.6 ml/min, proteinuria was 5.71 ± 2.56 g/day, and urinary red blood cells were 51.0 ± 37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P < 0.0001). The cases with steroid therapy significantly improved their prognosis, though their male-to-female ratio and blood pressure level measured at renal biopsy were significantly lower than in the cases without steroid therapy. Steroid therapy was particularly effective in cases with low-grade tubular atrophy and interstitial fibrosis (T-grade in Oxford classification). Without steroid therapy, lower eGFR and higher T-grade were independent risk factors for severe outcome by multivariate Cox regression. CONCLUSION: Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.

Clinical presentation & management of glomerular diseases: hematuria, nephritic & nephrotic syndrome.

Because the differential diagnosis for glomerulonephritis (GN) is broad, using a classification schema is helpful to narrow the causes of GN in a systematic manner. The etiology of glomerulonephritis can be classified by their clinical presentation (nephrotic, nephritic, rapidly progressive GN, chronic GN) or by histopathology. GN may be restricted to the kidney (primary glomerulonephritis) or be a secondary to a systemic disease (secondary glomerulonephritis). The nephrotic syndrome is defined by the presence of heavy proteinuria (protein excretion greater than 3.0 g/24 hours), hypoalbuminemia (less than 3.0 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease may be present. The nephritic syndrome is associated with hematuria and proteinuria and abnormal kidney function and carries poorer prognosis and is typically associated with hypertension. The predominant cause of the nephrotic syndrome in children is minimal change disease. The most common causes of nephritic syndrome are post infectious GN, IgA nephropathy and lupus nephritis. Chronic GN is slowly progressive and is associated with hypertension and gradual loss of kidney function. Treatment includes non-specific measure aimed at controlling hypertension, edema, proteinuria and disease modifying immunosuppression.

Semiología renal y genitourinaria en pediatría: segunda parte / Nephrologoy and urology semiology in children: second part

Entre las patologías renales en niños, se encuentra la injuria renal aguda; que es la pérdida súbita de la función renal; el síndrome nefrótico que es el espectro más grave de proteinuria; el síndrome nefrítico caracterizado por la riada edema, hematuria macro o microscópica e hipertensión arterial.

Among the renal pathology in children is acute kidney injury, which is the sudden loss of kidney function, the nephrotic syndrome is the most severe spectrum of proteinuria, the nephrotic syndrome characterized by the triad of edema, macro or microscopic hematuria and arterial hypertension.

Changes in glomerular mesangium in kidneys with congenital nephrotic syndrome of the Finnish type.

Congenital nephrotic syndrome of the Finnish type (NPHS1, CNF) is an autosomal recessive disease caused by mutations in a major podocyte protein, nephrin. NPHS1 is associated with heavy proteinuria and the development of glomerular scarring. We studied the cellular and molecular changes affecting the glomerular mesangium in NPHS1 kidneys. Marked hyperplasia of mesangial cells (MC) was mainly responsible for the early mesangial expansion in NPHS1 glomeruli. The levels of the proliferation marker, mindbomb homolog 1 and the major MC mitogen, platelet-derived growth factor, and its receptors, however, were quite normal. Only a small number of cells were positive for CD68 (marker for phagocytic cells) and CD34 (marker for mesenchymal precursor cells) in the NPHS1 mesangium. MCs strongly expressed alpha-smooth muscle actin, indicating myofibloblast transformation. The expression levels of the profibrotic mediators osteopontin and transforming growth factor beta were up-regulated in NPHS1 glomeruli by 3.2 and 1.6-fold, respectively, compared to the controls. The synthesis by MCs of the typical fibroblast products collagen I, fibronectin, and tenascin, however, was low, and the extracellular matrix increase was caused by the accumulation of a normal MC product, collagen IV. The results indicate that severe glomerular sclerosis can develop without major qualitative cellular or molecular changes in the mesangium.

Management of childhood onset nephrotic syndrome.

The therapeutic approach to childhood nephrotic syndrome is based on a series of studies that began with an international collaborative effort sponsored by the International Study of Kidney Disease in Children in 1967. The characteristics of children presenting with nephrotic syndrome have changed over recent decades with greater frequency of the challenging condition focal segmental glomerulosclerosis and a greater prevalence of obesity and diabetes mellitus, which may be resistant to glucocorticoids in the former and exacerbated by long-term glucocorticoid therapy in the latter 2 conditions. The Children's Nephrotic Syndrome Consensus Conference was formed to systematically review the published literature and generate a children's primary nephrotic syndrome guideline for use in educational, therapeutic, and research venues.