Idiopathic Minimal Change Nephrotic Syndrome Research Articles

Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n=4), cellulitis/fasciitis (n=4) and urinary tract infection (UTI) (n=4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio=6.1; 95% CI: 1.2-31.9, p=0.031) and non-remission by treatment (Hazard ratio=4.4; 95% CI: 1.2-15.6, p=.023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes

AbstractIt is currently considered that idiopathic minimal change nephrotic syndrome is an immune-mediated glomerular disease. Its association with classical Hodgkin lymphoma minimal change nephrotic syndrome (cHL-MCNS) suggests a molecular link, which remains to be elucidated. We analyzed the expression of cmaf inducing protein (c-mip) in lymphomatous tissues and kidney biopsy samples of patients with cHL-MCNS (n = 8) and in lymphomatous tissues of patients with isolated cHL (n = 9). Because c-mip affects the regulatory loop involving Fyn, we investigated possible structural defects in this signaling pathway, using laser capture microdissection, reverse transcription polymerase chain reaction, and Western blotting. We found that c-mip was selectively expressed in Hodgkin and Reed-Sternberg (HRS) cells and podocytes of patients with cHL-MCNS but is undetectable in patients with isolated cHL. We demonstrated that c-mip was specifically involved in the negative regulation of early proximal signaling through its interaction with phosphoprotein associated with glycosphingolipid-enriched microdomains and Fyn. We showed that the up-regulation of c-mip in cHL-MCNS was associated with a possible Fyn defect in HRS cells and podocytes. Moreover, we showed that c-mip was up-regulated in Fyn-deficient podocytes. c-mip may be a useful marker of cHL-MCNS and its induction reflects the dysregulation of proximal signaling.

Rituximab therapy for steroid-dependent minimal change nephrotic syndrome

We present a patient with steroid-sensitive but high-dose steroid-dependent nephrotic syndrome who was treated with rituximab. For 9 months following therapy she had undetectable CD19 cells in the peripheral circulation. She remained in remission during this period even though therapy was reduced to low-dose, alternate day prednisolone only. After 9 months, CD19 cells were once again detectable. Shortly after CD19 cells became detectable again she relapsed. We conclude that B-lymphocytes play a central role in the pathogenesis of idiopathic minimal change nephrotic syndrome (MCNS) and that rituximab may have a useful role in the management of steroid-dependent patients.

Gross hematuria in minimal-change disease nephrotic syndrome

Sirs, Idiopathic minimal-change nephrotic syndrome (NS) remains one of the commonest causes of NS in childhood, especially in the non-black population [1]. While transient microscopic hematuria has been described in 10–30% of children with minimal-change NS [2, 3], gross hematuria has not. In fact, gross hematuria in any child with idiopathic NS is exceedingly rare [4]. I recently took care of a child with new onset of NS, who at initial presentation, had gross hematuria. This Caucasian boy was admitted to the hospital at 9 months of age with anasarca, serum creatinine of 0.3 mg/dL, low serum albumin of 1.2 g/dL, elevated total cholesterol of 446 mg/dL and massive proteinuria (urine protein-to-creatinine ratio of 12.8); his coagulation studies and a renal ultrasound with doppler were normal. He was noted on admission to have pinkto red-colored urine that persisted throughout his 1-week hospital stay. The urine had a specific gravity of 1.005, a pH of 7.0 and 50–100 red blood cells per high-power field. Although the patient’s young age and hematuria were recognized to be atypical for idiopathic NS, since all his serologies were negative/normal (antinuclear antibody, complement C3 and C4, hepatitis B and C), it was elected to treat him empirically with oral steroids, without a renal biopsy. The patient was steroid responsive, although it took 1 month for his urine protein to become negative and for his serum albumin to normalize. Microscopic hematuria, which had persisted until then, also resolved. Since his initial presentation, he has had multiple relapses, all of which have been steroid responsive. The patient’s course was complicated by the development of bullous pemphigoid 1 year after the onset of NS. At that time, even though his renal disease was in remission, a renal biopsy was performed at the request of the dermatologist to rule out an immune complex-mediated disease. The renal biopsy demonstrated minimal-change disease with no immune complex deposits on immunofluorescence or on electron microscopy. His glomerular basement membranes were of normal thickness. This is the first report, to my knowledge, of a child with minimal-change NS presenting with gross hematuria. The purpose of this report is to add gross hematuria to the list of unusual manifestations in children with minimalchange NS and to re-emphasize that even in children with NS who some have atypical features, consideration should be given to administering a trial of empiric steroids before renal biopsy is performed. It is important to recognize, though, that our patient certainly did not fit the classic demographic profile for minimal-change NS in that he had infantile NS, and also since he eventually developed a rare skin disease, and therefore may not be representative of most children with idiopathic minimal-change NS.

Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses.

Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome in children and young adults. We investigated its clinical presentations, steroid responsiveness, subsequent clinical course and patterns of relapse in older adults in whom it was diagnosed after the age of 50 years. The clinical records of renal patients followed-up in a single out patient clinic were retrieved and those patients with biopsy-proven MCNS were included. Patients in the 18-50-year age range (Group A) at the time of biopsy were compared with those older than 50 years (Group B) with regard to baseline demographic data, clinical features and outcome of treatment. In all, 50 patients were studied, 35 in Group A (age at diagnosis: 38.8+/-11.91 years) and 15 in Group B (age at diagnosis: 70+/-6.85 years), with an overall follow-up duration of 72.08+/-63.42 months. Group B had a higher prevalence of hypertension and lower creatinine clearance at presentation, but the values of creatinine clearance for both groups were comparable with age-matched controls. One patient from Group B and two from Group A had spontaneous remission. Complete remission was achieved in 9.09, 45.45, 90.91 and 100% of Group B patients and 15.63, 62.5, 87.5 and 93.75% of Group A patients after 2, 4, 8 and 16 weeks of steroid therapy, respectively. The median time to complete remission and the duration of steroid treatment were similar for both groups. From Group B five patients and 22 patients from Group A relapsed during follow-up (P=0.055), with similar proportions of each group being early relapsers or frequent relapsers. The average number of relapses was 2.06 episodes for Group A, compared with 0.87 episodes for group B (P=0.062). Second agents were used in 20 Group A and four Group B patients (P=0.048). Complications of treatment were more common in Group A. None of the patients developed doubling of serum creatinine during follow-up. Clinical presentations of older patients with MCNS were similar to younger patients apart from the age-related decline of renal function and higher prevalence of hypertension. Both groups have similar steroid responsiveness, but older patients tend to have fewer relapses and require fewer second agents for treatment of relapses.

Urinary Excretion of Terminal Complement Complexes in Glomerular Disease

To evaluate renal terminal complement activation in patients with glomerular diseases, we measured terminal complement complexes (TCCs) in plasma and urine with sandwich enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against a C9 neoepitope expressed on TCC and a polyclonal antihuman C7 antibody. TCCs were detectable in plasma but not in urine in most of normal controls. In plasma, TCC levels were elevated in 4 of 22 patients with lupus nephritis and in 6 of 12 with membranoproliferative glomerulonephritis. However all patients with IgA nephritis, focal glomerulosclerosis, idiopathic membranous nephritis and idiopathic minimal change nephrotic syndrome (MC) showed normal values. In urine, TCCs were detectable in almost all patients with heavy proteinuria (greater than or equal to 100 mg/ml) except MC. The TCCs present in urine were partially purified by gel filtration using Sepharose 6B and were found to contain C5, C6, C7, C8, C9 and S protein by ELISA. Although the molecular weight of TCC is similar to that of IgM, the fractional excretion rate of TCC was about 100 times higher than that of IgM. These results suggest that TCCs detectable in urine contain SC5b-9 complexes and are mostly of renal origin.

Dysfunction of the monocyte-macrophage system in the idiopathic minimal change nephrotic syndrome.

We studied the function of phagocytes and the distribution of lymphocyte subpopulations in 23 patients with Idiopathic Minimal Change Nephrotic Syndrome. All the patients were in relapse at the time of the study. The latter was performed before specific therapy was started. Our control group consisted of 26 normal children who were studied while undergoing routine analysis prior to plastic surgery. Polymorphonuclear leukocytes from the patients showed no alterations in their ability to ingest and to kill candidas. On the contrary, peripheral blood monocytes had a normal phagocytic function with a decreased candidacidal activity when compared to normal controls (p less than 0.001). No correlation was found between serum immunoglobulin levels and the monocyte lytic function. The absolute number of B lymphocytes was significantly increased (p less than 0.05), whereas the absolute number of total lymphocytes, T lymphocytes and T4+ and T8+ cell subsets did not differ from those of the age-matched normal controls. Natural killer cells were functionally normal.

Glomerulonephritis Associated With Hepatitis B Virus Infection in Children

AbstractHepatitis B surface antigen (HBsAg) was identified by a reversed passive hemagglutination (RPHA) method in the serum of 13 of 15 patients with membranous glomerulonephritis (MGN), three of three Type III membranoproliferative GN (MPGN) proposed by Burkholder, three of 25 idiopathic minimal change nephrotic syndrome (IMCNS), three of 37 minor glomerular alterations with undetermined diagnosis (MGA) and none of 79 various other renal disease, in 266 Japanese children.Immunofluorescent studies showed granular deposition of Hepatitis B e antigen (HBeAg) in a similar pattern to that of IgG and β1C in the kidney of four patients with MGN, and of HBsAg in one with Type III MPGN. Eight of 13 MGN with positive serum HBsAg, two of three Type III MPGN and one of one MGA with positive serum HBs Ag had normalization of urinary findings during the observation period of one to eight years.Eight (5 MGN, 2 Type III MPGN and 1 MGA) of those with positive serum HBeAg showed seroconversion of HBeAg, and anti‐HBe appeared in five of eight as the urinary findings became normal. The normalization of urinary findings accompanied by seroconversion of HBeAg in the patients with MGA and with Type III MPGN suggests that HBeAg is the most important antigen involved in HB virus (HBV) associated GN including not only MGN but also Type III MPGN and MGA.

Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome.

To assess immunologic factors in the pathogenesis of idiopathic minimal-change nephrotic syndrome (INS), serum immunoglobulin concentrations were measured in 37 children with this syndrome and compared with those found in 36 with nephrotic syndrome secondary to chronic glomerulonephritis (CGN). Serum IgG and IgA levels were significantly reduced in nephrotic patients with either INS or CGN, IgG averaging 18.5 and 25.9 per cent of normal (P less than 0.001) and IgA 59.8 and 44.1 per cent of normal (P less than 0.01) respectively. Values increased after treatment of INS with prednisone, but mean values remained low. Serum IgM concentrations in INS averaged more than twice normal before, during, and after successful treatment with steroids. Patients with CGN did not have equivalent elevations of serum IgM. Thus, the primary defect in INS may be immunologic and could consist of deficiency in the T-cell function that mediates conversion of IgM synthesis to IgG synthesis.