Diffuse Mesangial Proliferative Glomerulonephritis Research Articles

Mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes in children with idiopathic steroid resistant nephrotic syndrome

Background: Many children with idiopathic steroid resistant nephrotic syndrome have been reported worldwide due to mutation of NPHS1, NPHS2, WT1 and LAMB2 genes. This study aimed to determine the frequency of mutation of NPHS1, NPHS2, WT1, LAMB2, COL4A5 and other genes and their association with renal histopathological patterns of idiopathic steroid resistant nephrotic syndrome patients. Methods: This cross-sectional study was conducted on 25 patients with idiopathic steroid resistant nephrotic aged 1-17 years in the Department of Paediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from July 2017 to June 2018. Next Generation Sequencing and mutation analysis were performed after DNA extraction from patients' venous blood lymphocytes. Histopathological study of renal tissue was done among 17 patients. Results: A little more than half (56%) of the patients were male. The mean age at the initial attack of nephrotic syndrome was 94.2 months. They mostly had minimal change disease (41%) and IgA nephropathy (12%). One subject had the NPHS2 gene mutation, histopathologically diffuse mesangial proliferative glomerulonephritis, and clinically stage-4 chronic kidney disease. Another subject had the COL4A5 gene mutation and focal segmental glomerulosclerosis. Both were male and had no familial renal disease, consanguinity, or hematuria. Conclusion: Children with idiopathic steroid resistant nephrotic syndrome showed NPHS2 and COL4A5 gene mutations. Histopathologically, they showed diffuse mesangial proliferative glomerulonephritis and focal segmental glomerulosclerosis.

MO248: A Renal Biopsy Might be a Mandatory Procedure in Patients with Hypertension and Decreased Renal Function Despite Normal Urinalysis Findings

Abstract BACKGROUND AND AIMS The most common cause of the end-stage renal disease is diabetes and hypertension. However, most centers do not try to find the cause of hypertension in patients with early-stage CKD but give antihypertensive medicine because most centers regard the cause as essential hypertension. Since blood pressure is regulated by the kidneys, we tried to find the cause of hypertension related to kidney disease. METHOD We carried out a single-center retrospective analysis of 1440 kidney biopsies performed for 8 years at a single center in Korea. All cases were done at the OPD level without admission, of which 367 cases (25.5%) showed hypertension/early-stage CKD with normal urinary findings at the time of renal biopsy. RESULTS The results are as follows in order of frequencies: IgA nephropathy (32.7%), mild focal nonspecific glomerulonephritis (GN) (17.7%), focal segmental glomerulosclerosis (FSGS) (15.3%), diffuse mesangial proliferative GN (12.8%), interstitial nephritis with tubular atrophy (7.6%), podocyte disease (3.3%) and membranous nephropathy (1.9%), and others include lupus nephritis, membranoproliferative GN, C1q nephropathy, C3GN, malignant hypertension (1.4%), etc. Most patients (95%) with hypertension/early-stage CKD were associated with chronic glomerulonephritis. Most patients with serious glomerular disease that may progress to ESRD, such as IgAN, FSGS and diffuse mesangial proliferative glomerulonephritis, have improved by aggressive immunotherapy. CONCLUSION In conclusion, before considering antihypertensive medicine in patients with early-stage CKD, a renal biopsy might be a mandatory procedure to save the kidney because more than 90% of cases are associated with glomerular disease.

Warfarin-Related Nephropathy Manifested as Diffuse Mesangial Proliferative Glomerulonephritis

Warfarin is associated with anticoagulant-related nephropathy (ARN), one of the potential side effects. This is evidenced by a progressively increasing number of detected cases of deterioration in the kidney function even in patients with normal baseline function (GFR {glomerular filtration rate}) in addition to the chronic kidney disease (CKD) patients who are already vulnerable to ARN. There has been a clinical correlation in a rapid decline of kidney function and international normalized ratio (INR) levels of greater than three. ARN is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. We want to emphasize the importance of monitoring kidney function regularly and adjusting the appropriate doses of warfarin. We present a case of a 57-year-old female who was on warfarin for the mechanical aortic valve, presented with acute kidney injury and supratherapeutic INR. Her renal biopsy showed diffuse mesangial proliferative glomerulonephritis.

Clinico-Pathological Correlations of Poststreptococcal Glomerulonephritis

Abstract Postinfectious glomerulonephritis is associated with bacterial, viral, fungal, and parasitic infectious agents and histologically appears most often as acute diffuse endocapillary or proliferative glomerulonephritis secondary infection with: group A streptococcus, streptococcus viridans, staphilococus aureus, diploccocus pneumoniae, Brucella melitensis, Salmonella typhi, Yershinia enterocolitica, Plasmodium falciparum, meningococcus, Mycoplasma, Klebsiella, varicella, variola, mumps. Less commonly, it appears as diffuse crescentic glomerulonephritis and a lot of infectious causes are incriminated like: streptococcus, legionella, varicella, Treponema pallidum or as focal crescentic glomerulonephritis: streptococcus A. It rarely appears as mesangiocapillary glomerulonephritis secondary infection with: streptococcus viridans, hepatitis C virus; diffuse or focal mesangial proliferative glomerulonephritis: hepatitis B virus, salmonella, adenovirus, influenza virus, salmonella; focal segmental, necrotizing and sclerosing glomerulonephritis: bacterial endocarditis; membranous glomerulonephritis: hepatitis B virus, syphilis, filarial, Mycobacterium, plasmodium falciparum; focal proliferative: Mycoplasma; mesangiolytic glomerulonephritis :Echo virus. Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific nephritogenic strains of group A beta-hemolytic streptococcus. The clinical presentation of PSGN varies from asymptomatic, microscopic hematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), edema, hypertension, and acute kidney injury. The prognosis is generally favorable, especially in children, but in some cases, the long-term prognosis is not benign. Managing a case of PSGN requires cooperation between internists, nephrologists, infectious disease consultants, pharmacists, and nursing staff, functioning as an interprofessional team, to provide excellent care for their patients.

Patterns of renal pathology in Chinese patients with systemic sclerosis undergoing renal biopsy at a tertiary medical center.

ObjectiveWe investigated renal injury characteristics in Chinese patients with systemic sclerosis (SSc) who had undergone renal biopsy.MethodsWe searched the medical records of patients with SSc who were hospitalized at Peking Union Medical College Hospital between January 1990 and August 2019. We analyzed the clinical characteristics and pathological results of these patients.ResultsWe identified 25 patients who had undergone renal biopsy. Of these patients, 10 had scleroderma renal crisis (SRC); one underwent renal biopsy twice (for diffuse mesangial proliferative glomerulonephritis and for SRC); two had antineutrophil cytoplasmic antibody-associated glomerulonephritis; one had immunoglobulin M nephropathy; one had minimal change nephropathy; seven had lupus nephritis; one had scleroderma renal crisis with comorbid lupus nephritis; and two had drug-related kidney injury (caused by aristolochic acid in one and D-penicillamine in the other). Acute tubular necrosis was observed in the patient taking oral aristolochic acid, while minimal change nephropathy was observed in the patient with D-penicillamine-induced renal injury.ConclusionsSRC was the most commonly encountered renal damage in patients with SSc. We recommend biopsy for patients undergoing treatment for SRC who have persistent renal injury with proteinuria, regardless of hematuria. Rheumatologists in Eastern countries should be aware of aristolochic acid nephropathy.

Complete Remission from C1q Nephropathy with Disappearance of C1q Deposition after Steroid Therapy

C1q nephropathy is a rare glomerular disease, defined by characteristic mesangial C1q immune deposition seen in immunofluorescence microscopy with no serological evidence of systemic lupus erythematosus. C1q nephropathy can be diagnosed with a subsequent biopsy, as with IgA nephropathy. There are some cases with an initial diagnosis of hematuria and proteinuria with minimal disease changes, focal segmental glomerulonephritis, and mesangial proliferative glomerulonephritis, but lacking C1q nephropathy, in which C1q deposition on immunofluorescence subsequently develops. We report a case that was diagnosed as diffuse mesangial proliferative glomerulonephritis, but a subsequent biopsy showed C1q nephropathy, with C1q deposition in both immunohistochemistry and electron microscopy (EM). We treated the C1q nephropathy with methylprednisolone and confirmed the disappearance of C1q depositions by both immunohistochemistry and EM in a follow-up biopsy. Keywords: Complement C1q; Glomerulonephritis; Methylprednisolone 중심 단어: Complement c1q; ì‚¬êµ¬ì²´ì‹ ì—¼; Methylprednisolone

Relationship between Fractional Excretion of Magnesium and Renal Histology in Glomerulonephritis

Progressive pediatric glomerularnephroses can lead to tubulointerstitial fibrosis (TIF) and chronic kidney disease (CKD). Fractional excretion of magnesium (FEMg) is a sensitive tubular function test (Ref). FEMg correlates positively with TIF (Ref). The purpose of the study was to correlate FEMg with renal histolopathology in pediatric glomerular nephrosis (GN). Sixty three cases, between 1-12 years, of biopsy diagnosed GN were included purposively in this cross sectional study from November 2008 to April 2010. Cases were taken from Department of Paediatric Nephrology, Dhaka Shishu (Children) Hospital and Department of Paediatric Nephrology, National Institute of Kidney Diseases & Urology, Sher-e-Bangla Nagar, Dhaka, Bangladesh. Minimal change disease (MCD) was most common at 27% and remaining 73% were other than MCD. The mean FEMg in MCD was normal (1.81 0.34%) but in other than MCD as a group it was significantly elevated (7.60 ± 19.23%; p<0.001). and significantly elevated separately in diffuse mesangial proliferative glomerulonephritis (3.96 ± 1.06%; p<0.001), focal segmental glomerulosclerosis (9.99± 4.45%; p<0.01), focal segmental proliferative glomerulonephritis (4.63 ± 2.29%; p<0.05) and crescentic glomerulonephritis (17.74 4.93%; p<0.01).

P97. Chronic kidney disease and pregnancy – A case report

Introduction Chronic kidney disease (CKD) is classified in five stages. Perinatal complications, such as preterm labor, preeclampsia and fetal growth restriction (FGR) are increased for all stages. In women with serum creatinine (sCr) above 2.5 mg/dL, the rate of preterm delivery is as high as 86%, mainly due to preeclampsia, which occurs in over 40%. The degree of renal insufficiency, rather than the underlying etiology, is the primary determinant of outcome. Women who become pregnant with high sCr level, are more likely to have a decline in renal function, than women who do not become pregnant, for the same sCr level. Hypertension and degree of proteinuria are also among the most important predicting factors. Fifty percent of women with sCr >1.5 mg/dL have a significant decline in glomerular filtration rate (GFR) in late pregnancy or early postpartum, with 20% of them progressing to end-stage renal disease (ESRD) within 6 months after delivery. Methods Review of literature about CKD and pregnancy and presentation of a clinical case. Results A 37-year-old African female, G3P1, engaged prenatal care at our hospital at 13 weeks gestation, with CKD – stage 4 (estimated GFR of 20.2 mL/min), for a baseline sCr level of 3.3 mg/dL. She had a nephrotic syndrome at 9 years old. Renal biopsy revealed diffuse mesangial proliferative glomerulonephritis, and was treated with prednisolone and cyclophosphamide. It progressed to CKD with secondary hypertension, treated with enalapril and amlodipine. During pregnancy she was medicated with methyldopa, amlodipine, darbepoetin, vitamin D, vitamin B, ferrous sulfate and calcium. Routine workup at 26 weeks revealed sCr 3.57 mg/dL, uric acid 9.4 mg/dL, without proteinuria. Pregnancy was uneventful until 34 weeks gestation, when she was admitted to with preeclampsia and worsening renal function. At admission, sCr 5.11 mg/dL, urea 174 mg/dL, uric acid 9.55 mg/dL and spot urine protein level of 200. Ultrasound revealed FGR (1st percentile), with altered Doppler velocimetry that motivated urgent cesarean delivery. The newborn weight was 1340g, female, Apgar score 10/9/10. At day 7 postpartum, she was discharged from the hospital, with sCr 5.34 mg/dL, urea 211 mg/dL and proteinuria 4+. Hemodialysis was programmed, as she awaits a donor for renal transplant. Conclusion Although pregnancy in women with CKD is associated with a high rate of live births, it is usually complicated by preeclampsia and fetal growth restriction. The higher the stage of CKD, the greater the probability of postpartum deteriorated renal function, with a significant proportion of women progressing to ESRD.

Collapsing focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus.

We present a case of a 36-year-old female from Ghana who presented with atypical chest pain and shortness of breath and was found to have bilateral transudative pleural effusion and trivial pericardial effusion. Further work-up revealed serological markers consistent with active lupus and negative HIV. She developed rapid deterioration of her renal function requiring dialysis. Her renal biopsy showed collapsing focal segmental glomerulosclerosis with diffuse mesangial proliferative glomerulonephritis, consistent with lupus nephritis class II along with tubular degenerative changes. She was started on high dose steroids and later on mycophenolate mofetil. Her renal function slowly recovered to baseline.

Correlation of fractional excretion of magnesium with steroid responsiveness in children with nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) patients are candidates for other alter-native drug regimes, and the non-responsiveness to steroid is more common among glomerulo-nephritides other than minimal change disease. Without performing biopsy and proper renal histology, progression of the disease cannot be assessed. Fractional excretion of magnesium (FE Mg) has been found to correlate directly with various renal histologies. The aim of this study is to evaluate the relationship of FE Mg in children with the histological pattern in SRNS. In this prospective observational study, 40 children of nephrotic syndrome, both with the first episode as well as relapse, aged 1-12 years were included in the study. Of them, 20 were steroid-responsive cases and 20 were steroid-resistant cases. FE Mg was determined in all the patients and renal histology was performed in the steroid-resistant cases. A correlation was found between FE Mg and renal histology. Data were analyzed in SPSS program version-16. Comparison of two groups was performed by the Fisher exact test and unpaired t test. P-value less than 0.05 were considered to be significant. The results of histo-pathology showed that the mean difference in FE Mg was significant (P <0.001), as FE Mg was 7.0 ± 2.3% in mesangiocapillary glomerulonephritis, 6.9 ± 1.3% in focal segmental glomerulosclerosis, 4.7 ± 0.6% in immunoglobulin M nephropathy, 4.5 ± 1.2% in focal segmental proliferative glomerulo-nephritis, 4.4 ± 1.6% in minimal change disease, 4.2 ± 0.4% in diffuse mesangial proliferative glome-rulonephritis and 3.8 ± 1.3% in mesangial proliferative glomerulonephritis. There was a statistically significant difference between FE Mg in steroid-resistant nephrotic syndrome (4.9 ± 1.9) and steroid-responsive syndrome (1.2 ± 0.3). FE Mg is a simple, minimally invasive screening marker for SRNS, and is an early predictor of clinical outcome. It can be considered as an initial investigation where biopsy cannot be performed or indications are not clear.

Female polysomy-X and systemic lupus erythematosus

ObjectivesSystemic lupus erythematosus (SLE) occurs more commonly in females than in males. Recent evidence suggests that genetic factors transmitted by the X-chromosome may confer increased risk for autoimmune disease in general, and for SLE in particular. It is therefore possible that X-chromosome polysomy might confer further increased risk for lupus. In addition to describing the clinical and immunologic features of a young woman with polysomy-X and SLE, we sought to review all other published cases associating female or male polysomy-X with SLE or other forms of autoimmunity. MethodsWe report a case of a prepubertal girl with polysomy-X and SLE. We performed a systemic literature review for cases of polysomy-X and SLE and summarize previously published cases. In addition, we reviewed reports concerning the possible association between SLE and other connective tissue diseases and male polysomy-X. ResultsAn 11-year-old girl with tetrasomy-X (48 XXXX karyotype) presented with prolonged fever. Workup led to the diagnosis of SLE, and subsequent renal biopsy revealed mild diffuse mesangial proliferative glomerulonephritis. Two additional cases of SLE in women with 47 XXX and one of 48 XXXX karyotype were found in a literature review and compared to the present case. We identified studies that found X-chromosome polysomy to be over-represented in male patients with SLE and case descriptions of connective tissue diseases occurring in patients with polysomy-X. ConclusionNo consistent pattern of disease was observed in female polysomy patients with SLE. Taken together with the data concerning the frequency of polysomy-X among males with SLE, our findings provide additional support for the hypothesis that X-chromosome polysomy may confer increased susceptibility to SLE. Molecular mechanisms that might account for this phenomenon are discussed.

Pattern of glomerular diseases among adults in Rajshahi, the Northern Region of Bangladesh

To obtain a recent and comprehensive insight into the pattern of glomerular diseases in the Bangladeshi population, we studied 95 adequate renal biopsies done during July 2008 to June 2009, by light and direct immunofluorescence microscopy in the Department of Pathology, Rajshahi Medical College, Northern Region of Bangladesh. Of these, 38 (40%) were males and 57 (60%) were females, with a male to female ratio of 1:1.5. The most frequent clinical presentation was nephrotic syndrome (67.37%). Primary glomerular disease accounted for 91.25% of all glomerular disease and, of them, focal and segmental mesangial proliferative glomerulonephritis was the most common histological lesion in 29.47%. Diffuse mesangial proliferative glomerulonephritis (GN) was the second most common lesion (15.79%), followed by focal segmental GN (11.58%), minimal change disease (10.53%), membranous GN (7.37%), IgA nephropathy (6.85%), chronic sclerosing GN (2.11%) and crescentic GN (2.11%). Lupus nephritis was the most prevalent among secondary GN.

Histomorphometric study in children with idiopathic nephrotic syndrome.

From 1981 to 1987, renal specimens obtained from 91 children with idiopathic nephrotic syndrome were categorized into 5 histologic subgroups, according to the WHO classification. We analyzed differences in the ratios of the size of the mesangial stalks and attached capillary, including the Bowman's space between the capillary tufts (E), mesangial matrix (Mx), and approximate capillary lumens (E-Mx) to the whole glomerular area of these subgroups using the histomorphometer-IBAS. Focal segmental glomerulosclerosis with diffuse mesangial proliferation (FSGS + DP) had the largest matrix area (Mx/G > 0.5), and smallest capillary lumen size (E/G-Mx/G) (0.3474 +/- 0.0702). On the contrary, FSGS with minimal change (FSGS + MC) had the smallest mesangial matrix (Mx/G), 0.2834 +/- 0.07726, but preserved a larger capillary lumen (0.427 +/- 0.1215). The approximate size of capillary lumens, from the smallest to the largest, was in the following order: FSGS + DP, diffuse mesangial proliferative glomerulonephritis (DPGN), focal segmental proliferative glomerulonephritis (FSPGN), FSGS + MC and minimal change nephrotic syndrome (MCNS). The ratio of the total number of mesangial cells to the area of the whole glomerulus (MCN/G) derived from the light microscopic examination was parallel to the value of Mx/G obtained by the histomorphometric technique. In summary, we introduced the histomorphometric technique using the histomorphometer-IBAS for quantitative measurement of various areas in the glomeruli. The data derived from the system is compatible with those obtained by experienced nephrologists, suggesting that the histomorphometric technique is helpful in histopathology. It is hoped that this new methodology will be used more extensively in the near future.

The Spectrum of Adult Postinfectious Glomerulonephritis in the New Millennium

Background. Postinfectious glomerulonephritis is rare in adults. The characteristics of the disease now differ from what were described decades ago. The goal of this study is to illustrate the clinicopathological spectrum of the disease in the modern era. Methods. Between July 2000 and June 2008, 20 adult cases of postinfectious glomerulonephritis were identified at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. Results. There were 14 males and 6 females. The mean age was 61 years. All patients developed acute renal failure, and the majority (65%) required dialysis support during the disease course. Hypocomplementemia was present in 60% of patients. The most frequently identified infectious agent was Staphylococcus (60%). Histological characteristics showed two distinct patterns of glomerulonephritis: diffuse endocapillary proliferative glomerulonephritis (65%) and focal mesangial proliferative glomerulonephritis (35%). There were no significant differences in the clinical presentation and outcome between the two groups. However, glomerular neutrophil infiltration was more commonly present in diffuse endocapillary proliferative pattern (p = 0.017). The percentage of patients with focal mesangial proliferative pattern significantly increased over time (p < 0.001). At the last follow-up, 6 patients (30%) had died, 6 (30%) were in complete remission, 4 (20%) had partial remission with renal insufficiency, and 4 (20%) were on chronic dialysis. Conclusions. Our data suggested that Staphylococcus had become the leading pathogen in adult postinfectious glomerulonephritis over the past 10 years. Furthermore, atypical histological feature with focal mesangial proliferative pattern was increasingly identified over time. The prognosis was still guarded, carrying a considerable mortality rate and risk for developing chronic renal failure.

Low-density lipoprotein apheresis in a pediatric patient with refractory nephrotic syndrome due to focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) often leads to refractory nephrotic syndrome (NS). A high level of low-density lipoprotein (LDL) is a risk factor for the progression of NS. An 8-year-old girl presented with severe proteinuria refractory to steroid therapy. She was diagnosed with non-IgA diffuse mesangial proliferative glomerulonephritis. Oral prednisolone, methylprednisolone (mPL) pulse therapy, and cyclosporine and cyclophosphamide therapy failed to achieve remission. Follow-up renal biopsy revealed FSGS. Her serum level of LDL was high, and LDL-apheresis (LDL-A) was performed five times, followed by mPL pulse therapy. Urinary protein decreased from 2-4 g x day(-) to 0.5-1.0 g x day(-). LDL-A may be beneficial in the treatment of multidrug-resistant FSGS.

A single-center study of C1q nephropathy in children

C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.

Steroid-resistant nephrotic syndrome: long-term evolution after sequential therapy

We present a retrospective study of 30 children of mean age 3.02 +/- 1.81 years with steroid-resistant nephrotic syndrome (SRNS) treated with intravenous injection of methylprednisolone plus orally administered prednisone; 24 children also received cyclophosphamide (CP). Sixteen were resistant to steroids from the beginning, and 14 after a mean of 11.26 +/- 16.61 months. The initial histological diagnosis was: 18 minimal change disease (MCD), 11 focal segmental glomerulosclerosis (FSGS) and one diffuse mesangial proliferative glomerulonephritis (DMPG). Total remission was achieved in 22 patients (73.3%), partial response in three (10%) and no response in five (16.6%), two of whom were brothers carrying an NPHS2 gene double mutation. There was no difference in response between the MCD and FSGS patients; the only patient with DMPG did not respond. Only initial resistance was a sign of bad prognosis. At follow-up (6.4 +/- 3.6 years from last pulse), 21/22 were still in remission, 14/21 were without treatment. Six patients required cyclosporine or mycophenolate mofetil because of steroid dependence. Two non-responders developed end-stage renal failure (ESRF); the remaining patients maintained normal glomerular filtration. The treatment was well tolerated. In conclusion, most of the patients treated with sequential therapy consisting of methylprednisolone (MP) (100%) and CP (80%) showed remission and preserved renal function, but 20% developed steroid dependence.

The development of sarcoidosis with the use of alemtuzumab – clues to T‐cell immune reconstitution

The development of sarcoidosis with the use of alemtuzumab – clues to T‐cell immune reconstitution

Does cyclosporine achieve a real advantage for treatment of idiopathic nephrotic syndrome in children? A long-term efficacy and safety study

Cyclosporine (CsA) was found to be efficient in decreasing proteinuria in both steroid-dependent and steroid-resistant nephrotic patients. We aimed to explore the potential long-term benefits and hazards of CsA and their predictors among a large group of nephrotic patients. In this retrospective analysis, we included 197 pediatric patients with idiopathic nephrotic syndrome (INS) of whom 103 were steroid dependent and 94 steroid resistant. CsA induced complete remission in 132 (67%) and partial response in 13 (6.6%). Cyclosporine was received for a period of 22.16 +/- 12.21 months. Univariate analysis showed that the response to CsA was significantly better in steroid-dependent children, in minimal change disease (MCD), diffuse mesangial proliferative glomerulonephritis (DMP) and focal segmental glomerulosclerosis (FSGS) than in other pathological lesions and in those who had lower quantities of pretreatment proteinuria. Only the prior response to steroids and concomitant use of ketoconazole with CsA were valid predictors for better response to CsA with multivariate analysis. Discontinuation of the drug in 40 patients resulted in relapse in 26 patients while the remaining 14 patients maintained remission. Renal dysfunction developed in 18 patients of whom 12 recovered completely on drug discontinuation. Thirty-seven patients developed hypertension. Multivariate analysis showed that all side-effects were significantly more prevalent in CsA-resistant patients. CsA is effective and well tolerated in the long-term treatment of INS in children, however two thirds of cases showed relapse after CsA discontinuation.

Treatment aspects of primary nephrotic syndrome in adults

Strict therapy protocol, which would be used universally for certain morphological forms of primary nephrotic syndrome, does not exist. The aim of the study was to show the effects of used therapy protocol in treatment of primary nephrotic syndrome at the Institute of Nephrology, Clinical Center University of Sarajevo in period of 2000-2005. The retrospective analysis covered 48 patients (17 women and 31 men) with idiopathic nephrotic syndrome, where pathomorphological changes were proved by kidney biopsy. Minimal change disease was confirmed with 6 (12.5%) patients. All patients were initially treated with corticosteroids with dose of 1 mg/kg of body weight. Five patients were in the group of primary responders (83.3%) with long term total remission, and 1 patient (16.6%) was a primary responder with 3 relapses in 8 months with a therapy of corticosteroids and bolus of cyclophosphamide. Diffuse mesangial proliferative glomerulonephritis was shown in 13 patients (27.1%). Seven patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients). Six patients were treated with corticosteroids and one-month of bolus cyclophosphamide during half of year (10-5 mg/kg of body weight). Total remission was achieved in 37,9% of the patients. The IgA nephropathy presented with the nephrotic syndrome was shown in 10.4% (5) of the patients. Three patients from this group were treated with corticosteroid therapy (1 mg/kg of body weight for 4 weeks, followed by 0,5 mg/ kg of body weight until therapeutical response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients) and.2 patients with corticosteroids and cyclophosphamide (1.5 mg/kg of body weight) during 6 months. Complete remission of nephrotic syndrome from this pathomorphological category was achieved in 2 patients. Membranoproliferative glomerulonephritis was shown in 6 patients (12.5%). All were treated with corticosteroids plus bolus of cyclophosphamide. Partial remission was achieved in one patient. Membranous glomerulonephritis was confirmed in 18 patients (37.5 %). Combined therapy of corticosteroids and bolus of cyclophosphamide was used in 7/18 patients, in 2/18 patients therapy of corticosteroids and per os cyclophosphamide (2 mg/kg of body weight) and in 9/18 patients cyclosporine therapy (3 mg/kg of body weight). Complete remission was achieved in 38.8% of the patients. A high percentage of achieved remissions of primary nephrotic syndrome in adults shows the efficiency of immunomodulating therapy used. Membranoproliferative glomerulonephritis still remains a therapy problem.