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The changing pattern of glomerulonephritis in Singapore over the past two decades.

This study reviews the pattern of glomerulonephritis (GN) in Singapore over the past 2 decades. In the earlier decade the pattern was typical of most Asian countries with mesangial proliferative GN (Mes GN) (56%) as the most common form of primary GN including the nephrotic syndrome (40%). In the 2nd decade the pattern undergoes a change. Though Mes GN is the commonest primary GN (42%), the commonest form of nephrotic syndrome is now minimal change disease (30%) with Mes GN decreasing to 25% among all primary nephrotic syndromes. Both minimal change and focal global sclerosis account for 50% of steroid/cyclophosphamide responsive GN today. Membranous GN though still uncommon, has increased from 3% (1st decade) to 6% (2nd decade) (p < 0.01). IgA nephritis is still the commonest primary GN occurring in Singapore (42% of all primary GN in the 1st decade and 45% in the 2nd decade). The present pattern of GN in Singapore, though, still predominantly Asian with the preponderance of mesangial proliferative GN with a relatively low incidence of membranous GN contrasts with the pattern in the West where membranous GN is the commonest form of primary GN. Even the incidence of FSGS has not increased as in the West where there is a rising incidence. The underlying basis for most GN in Singapore as in other Asian countries and elsewhere is antigen-driven: infective antigen as well as food or other allergens.

Adolescent↗

An analysis of 4,514 cases of renal biopsy in Korea.

To evaluate the distribution and changing patterns of renal diseases in Korea, a total of 4,514 cases of renal biopsy collected over a 23-year period between 1973 and 1995 were reviewed. Of 4,200 cases excluding 314 unsatisfactory biopsies, adult cases comprised 59.5% and pediatric cases, 40.5%. The male to female ratio was 1.5:1 in adults and 2.2:1 in children. Glomerulonephritis (GN) comprised 80.0% of the total. The most common primary GN in adults was minimal change disease (MCD) (26.6%), followed by IgA nephropathy (IgAN) (22.1%), membranous GN (MGN) (11.8%), and membranoproliferative GN (MPGN) (5.9%). In children, the primary GN incidence rates were MCD (24.8%), IgAN (10.3%), poststreptococcal (including postinfectious) GN (PSGN) (8.6%), and focal segmental glomerulosclerosis (FSGS) (4.0%). The most common secondary GN in adults was lupus nephritis and in children Henoch-Schonlein purpura nephritis. The most common cause of nephrotic syndrome was MCD in both adults and children, followed by MGN and FSGS. The elderly, aged sixty years and older, comprised 2.7% of cases and recorded equal numbers of MCD and MGN. The proportion of the biopsies found to be seropositive for HBs antigen was 27.9%, and these showed either MGN or MPGN pattern. Repeat biopsy was performed in 168 patients, due to previous biopsy failure in 15.5%. When the primary GN cases were analyzed at 5-year intervals, the prevalence of PSGN, which was greater than 25% during the 1973-1982 period, decreased abruptly in children thereafter, whereas the prevalence of FSGS increased slowly since the 1988-1992 period in both adults and children. The decrease of PSGN and the increase of FSGS suggest a role for socioeconomic and environmental factors in Korea.

Adult↗

Pattern of glomerulonephritis in Singapore children--a renal biopsy perspective.

This study was aimed at determining the pattern of glomerulonephritis (GN) in Singapore children from a histopathological perspective. Fifty-seven consecutive children, aged between 10 weeks to 16 years, who underwent a renal biopsy at the Departments of Paediatrics, National University of Singapore and Singapore General Hospital over an 8 year period were studied. The main indications for biopsy were nephrotic syndrome (67%), recurrent gross haematuria (16%), nephritic syndrome (7%), and renal failure (10%). Primary GN occurred in 81%, while secondary GN was seen in 19%, the most common being lupus nephritis. Of the primary GN, minor abnormalities was the most common (22%), followed by focal global sclerosis (20%), focal segmental glomerulosclerosis (17%), diffuse mesangial proliferative GN (11%), focal mesangial proliferative GN (9%), membranous GN (7%), diffuse endocapillary GN (4%), diffuse sclerosing GN (4%), diffuse mesangial sclerosis (4%), and diffuse crescentic GN (2%). Immunofluorescent examination was performed in 50 children. IgA nephropathy was diagnosed in 17% of the patients with primary GN. Of the children with primary nephrotic syndrome due to minimal change disease or focal global sclerosis, about half had IgM mesangial deposits. Of 47 patients who were followed up, 9 developed chronic renal failure, of which 7 reached end-stage disease (4 have died, while 3 are on chronic dialysis). Three other patients died of other complications. The histopathological findings influenced the therapeutic decision in 49% of our patients. In summary, the pattern of GN in our cohort of patients tended to reflect more severe glomerular lesions, mainly due to our criteria of selection for renal biopsy.

Adolescent↗

Urine of patients with nephrotic syndrome contains the plasma type of PAF-acetylhydrolase associated with lipoproteins.

BACKGROUND: Platelet-activating factor (PAF) is a proinflammatory phospholipid mediator involved in the pathogenesis of glomerulonephritis (GN). In plasma, PAF is hydrolyzed and inactivated by PAF-acetylhydrolase (PAF-AH), an enzyme associated with lipoproteins, mainly with the low-density lipoprotein. PAF-AH activity has been found in urine of patients with primary GN, however the source and type of urinary PAF-AH remain unknown. We characterized the type of PAF-AH excreted in the urine of patients with primary GN and studied the possible relationship of this enzyme with the lipiduria and proteinuria observed in these patients. METHODS: Eighteen patients with primary GN (8 with nephrotic syndrome (NS) and 10 with non-nephrotic range proteinuria (NNRP)) and 20 normolipidemic age- and sex-matched controls participated in the study. PAF-AH activity in plasma, in urine and in individual lipoprotein particles was determined by the trichloroacetic acid precipitation procedure, whereas the PAF-AH protein was detected by Western blotting analysis. Plasma and urine lipoproteins were fractionated by gradient ultracentrifugation and characterized by Western blotting analysis. RESULTS: Plasma PAF-AH activity was higher in NS patients compared with NNRP patients and controls, whereas the enzyme activity associated with high-density lipoprotein was significantly lower in both patient groups compared with controls. PAF-AH was detected only in the urine of NS patients. It was the plasma type of PAF-AH and was associated with lipoprotein particles. Enzyme activity was also positively correlated with urine cholesterol levels. CONCLUSION: Urine of NS patients contains the plasma type of PAF-AH, which is related to the extent of lipiduria and is associated with urine lipoproteins.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Glomerulonephritis in Singapore: an overview.

The pattern of glomerulonephritis (GN) consisting of 1057 renal biopsies is presented. Primary GN accounted for 91% and secondary GN 9% of which the commonest is lupus nephritis. Asymptomatic haematuria and proteinuria was the commonest mode of presentation (41%), gross haematuria 9%, nephrotic syndrome 29% while 5.5% presented with renal impairment and 4.3% with hypertension. Mesangial proliferative GN is the commonest histopathological lesion forming 66% of all primary GN. Minimal Lesion, Focal Global Sclerosis and Focal Segmental Glomerulosclerosis accounted for 7% each. Membranous GN was uncommon (3%) while Mesangiocapillary GN, Diffuse Endocapillary GN and Crescentic GN were even rarer. If the presenting feature was asymptomatic haematuria and proteinuria the likely diagnosis was IgA nephritis, and, if nephrotic syndrome it was likely to be Idiopathic Mesangial Proliferative GN but with negative staining on immunofluorescence. The course and prognosis of the various forms of GN are next discussed. Nephrotic syndrome with Minimal Lesion has an excellent prognosis while Crescenteric GN usually carries a grim prognosis. Finally, factors affecting the progression of IgA nephritis, the commonest form of GN occurring in Singapore are examined. Patients who developed renal failure ran two different courses; one was a slowly progressive course over an average of 7.7 years before reaching end stage renal failure (ESRF), while the other was a more rapid decline to ESRF within an average of 3.3 years where severe uncontrolled hypertension seemed to be the major adverse factor. 9% had renal impairment at the end of a follow up of 50 + 1/2 - 34 months while 5% progressed to ESRF. The cumulative renal survival was 91% after 6 years with no further loss up to 14 years. Unfavourable long term prognostic indices were proteinuria of more than 2 gms, hypertension, crescents on renal biopsy, severe segmental sclerosis and medial hypertrophy of blood vessels.

Adolescent↗

[Course of the annual incidence of primary glomerulopathies in a population of 400,000 inhabitants over a 10-year period (1976-1985)].

Between January 1976 and December 1985, renal biopsy was indicated in 663 adults (greater than 15 yrs) patients who were born and lived in a rural area of 400,000 inhabitants. Annual incidence (AI) was 16.5/100,000. Primary GN was diagnosed in 418 pts (63%) corresponding to a prevalence (P) for 10 yrs of 1/1000. The results have been compared for two periods: A (1976-1980) and B (1981-1985) for which the number of patients with primary GN was similar (205 vs 213, AI: 10.3 vs 10.6/100,000). Sex-ratio M/F (2.1 vs 1.8) and mean age (+/- SD) at the time of renal biopsy (45 +/- 17) were not different. P (%) among primary GN, P (nb/1000) among global population, AI (nb/100,000) and sex-ratio (A vs B) were evaluated for each histological type: lipoid nephrosis (MC and HSF): 9.8%, 0.1/1000, 1.2 vs 0.8/100,000 (ns), 1 vs 1.5 (ns). Membranous nephropathy 12.4%, 0.13/1000, 1.1 vs 1.5/100,000 (ns), 1.75 vs 0.8 (less than 0.02). IgAGN (Berger): 27%, 0.28/1000, 2.6 vs 3/100,000 (ns), 3 vs 3.3 (ns). IgAGN (Schönlein-Henoch): 5%, 0.05/1000, 0.45 vs 0.6/100,000 (ns), 3 vs 5 (ns). MPGN: 5.9%, 0.06/1000, 1 vs 0.25/100,000 (less than 0.01), 2.3 vs 1.5 (ns). Post streptococcal AGN: 2.8%, 0.03/1000, 0.55 vs 0.05/100,000 (less than 0.01). Non post-streptococcal AGN: 6.7%, 0.07/1000, 0.65 vs 0.75/100,000 (ns), 1.2 vs 0.6. Idiopathic crescentic GN: 4.7%, 0.05/1000, 0.25 vs 0.75/100,000 (less than 0.01) 1.5 vs 1.5. S and F proliferative GN: 1.9%, 0.02/1000, 0.15 vs 0.25/100,000 (ns), 2 vs 0.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Is there a hepatitis B virus (HBV) associated glomerulonephritis? Evaluation of the significance of HBV antigen deposition in the kidney].

In order to clarify the relationship between HBV infection and glomerulonephritis (GN) and to explore the significance and mechanism of HBV deposition in the kidney, renal biopsies from 60 patients with various forms of GN and HBV antigenemia (Agb) were compared with those from 59 age, sex and renal histology matched controls. The biopsies were studied with 4 layer PAP immunoperoxidase and immunofluorescence techniques using monoclonal antibodies to HBV surface (HBsAg), core (HBcAg) and e (HBeAg) antigens. All the 3 HBV antigens were detected in the kidneys of greater than 67% of the patients with membranous nephropathy and in greater than 64% of the cases with lupus nephritis regardless of the presence of HBV Agb or not. In certain patterns of primary GN, including mesangioproliferative GN, IgA nephropathy and membrano-proliferative GN. HBsAg in the kidney was more common in patients with HBs Agb than those without (47.7% vs 20.5%, P less than 0.05). No difference in HBcAg or HBeAg deposition was observed in patients with or without HBV Agb Granular deposition of HBV antigens was shown in the same pattern as that of Ig(s) and complement deposition. Renal HBV deposition correlated closely with the extent of other deposits. We concluded that the deposition of HBV antigens in kidney is often non-specific, although HBsAg is more commonly seen in some HBsAg carriers with primary GN Massive immune complex deposits seem to be the prerequisite of renal HBV deposition. The role of HBV in the development of GN is therefore not confirmed and further evaluation is needed for "HBV-TC nephritis".

Adolescent↗

Systemic Proteome Profiling to Differentiate Primary Glomerular Diseases.

KEY POINTS: Plasma proteome profiling identified distinct signatures across biopsy-proven primary glomerular disease subtypes. An elastic net model using 93 proteins classified primary glomerular disease subtypes and controls, with external validation. Integrating proteomics with machine learning yields biologically interpretable insights in primary glomerular diseases. BACKGROUND: Primary GN is a heterogeneous group of kidney disorders where understanding of their pathophysiology remains incomplete. Despite the diagnostic potential of high-throughput proteomics, constrained proteomic depth and a reliance on binary comparisons have left the feasibility of using systemic signatures to differentiate multiple GN subtypes largely unexplored. METHODS: To identify protein signatures that noninvasively differentiate major primary glomerular disease subtypes and provide mechanistic insights, we performed large-scale systemic proteome profiling of 5416 plasma proteins via Olink Explore HT in a discovery cohort ( n =147) and an external validation cohort ( n =85) of Korean participants (mean age, 41&#xb1;13 years; 46% female). The study population included patients with four GN subtypes-focal segmental glomerulosclerosis, IgA nephropathy, minimal change disease, and membranous nephropathy-alongside healthy controls. We developed a machine learning (ML) model using logistic regression with elastic net regularization to classify disease groups based on proteomic profiles and evaluated its performance in the independent validation cohort. RESULTS: Plasma proteome profiles were distinct among disease subtypes, emerging as a significant source of data variation independent of conventional markers such as eGFR or proteinuria levels. The ML model performed robustly in both the discovery and validation cohorts, achieving an area under the receiver operating characteristic curve >0.8 for differentiating minimal change disease, membranous nephropathy, and IgA nephropathy. The model, even without clinical information, correctly identified 93% of minimal change disease cases (14 of 15) and 63% of IgA nephropathy cases (20 of 32), but its performance was limited for focal segmental glomerulosclerosis, with only 21% of cases (three of 14) correctly classified. Functional analysis of key proteins highlighted distinct biologic pathways, such as hemostasis in minimal change disease. CONCLUSIONS: We identified distinct systemic proteome signatures for primary glomerular diseases, where disease subtype served as a major determinant of proteomic variance alongside conventional clinical markers. ML models demonstrated robust discriminatory performance for minimal change disease, membranous nephropathy, and IgA nephropathy, underscoring the potential for proteome-based classification.

Humans↗

Genetic variants of microsomal metabolism and susceptibility to hydrocarbon-associated glomerulonephritis.

Hydrocarbon (HC) exposure can play a role in the development of chronic glomerulonephritis (GN). Interindividual variations in various metabolizing enzymes may influence HC biotransformation, and hence susceptibility to HC-associated GN. We evaluated the role of human genotypic polymorphism in HC-associated GN, in 41 patients (30 male, 11 female) with primary GN (17 diffuse mesangial proliferative GN, 12 focal segmental GN, 11 membranous GN, one membranoproliferative GN) and 60 (46 male, 14 female) healthy controls. Genotypic polymorphisms of (CYP) P450 2D6 (CYP2D6), glutathione S-transferases mu (GSTM1) and theta (GSTT1) and N-acetyltransferase (NAT-2) were determined using polymerase chain reaction analysis of white-blood-cell DNA. HC exposure scores were determined using a validated questionnaire, and were significantly elevated in GN patients compared to controls. While no significant differences in the various genotypic frequencies were observed in the GN group overall, compared to controls, there was a significant increase in GSTM1 null (n = 10) to GSTM1 wild type (n = 1), and NAT fast (n = 10) to slow (n = 1) acetylators, in the membranous GN group compared to controls (p < 0.05). These results suggest a possible role for GSTM1 null and NAT fast acetylator in the development of HC-associated membranous GN.

Acetyltransferases↗

Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology.

BACKGROUND: Children's renal biopsy data were gathered for 3 consecutive years (1992-1994) by the Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology, which opened a paediatric section of the Italian Registry of Renal Biopsies. MATERIALS: The Registry recorded the histological diagnosis and the clinical data at renal biopsy of 432 children < or = 15 years old (mean age 8.96 +/- 3.7 years). RESULTS: The most common glomerulonephritis (GN) at renal biopsy was idiopathic IgAGN (18.8%) and the most frequent secondary GN was Henoch-Schönlein purpura (HSP) nephritis (11.6%). Minimal-change disease (MCD) accounted for 11.6%, focal and segmental sclerosis (FSG) 8.5%, mesangial proliferative GN (MPGN) 9.5%, membranoproliferative GN 5.5%, and thin-membrane disease 5%. Lupus nephritis was diagnosed in 5% and Alport's GN in 3.9% of the cases. The annual incidence of primary GN in Italian children was 11.1 cases per million children population (p.m.c.p.), IgAN accounting for 3.1 cases, MCD 2.3, and HSP nephritis 1.9 cases p.m.c.p. respectively. Italian children underwent renal biopsy because of isolated microscopic haematuria in 19.3% of the cases, non-nephrotic proteinuria with or without microscopic haematuria in 31.2%, and nephrotic-range proteinuria in 34.2%, less frequently (15.3%) because of acute or chronic renal failure. Children with persistent isolated microscopic haematuria had most frequently IgAN (34.9%) or thin-membrane disease (25.3%), while those with non-nephrotic proteinuria had IgAN (30.4%) and HSP nephritis (23%). In cases with nephrotic proteinuria renal biopsy showed MCD in 34.5% of the cases, FSG in 16.9%, and MPGN in 12.2%. When renal biopsy was performed in chronic renal failure, chronic interstitial renal disease was detected in 62.5% of the cases. CONCLUSIONS: This National Registry provides data on the indications for performing renal biopsy in Italian children and on the frequency and annual incidence of histological lesions detected. IgAN, primary or related to HSP, was the most common nephritis in Italian children undergoing renal biopsy.

Adolescent↗

[Clinico-morphological characteristics and prognosis of glomerulonephritis in chronic alcoholism].

The paper is concerned with the results of a long-term study with clinicomorphological correlations of 86 patients with alcoholic glomerulonephritis (GN), i. e. 12% of all morphologically verified cases of primary GN. GN clinical features in alcoholism were painless microhematuria, moderate hyperuricemia, frequent combination with the alcoholic involvement of the other organs and the elevated blood serum IgA level. An important diagnostic sign in alcoholic GN was a positive clinicolaboratory time course in abstinence. A morphological study showed prevalence of mesangioproliferative GN with deposits containing IgA and C3, often with a noticeable tubulointerstitial component and fibroplastic glomerular transformation. The accumulation of podocytes and nephrocytes of intermediate filaments in the cytoplasm should be regarded as an important morphological feature of alcoholic GN. An unfavorable course of alcoholic GN with an outcome into chronic renal failure was observed in 35% of the patients. Prognostically unfavorable signs were the age under 40, the presence of considerable proteinuria (over 1 g/day), the nephrotic syndrome, the detection of the glomerular immune complexes, a tubulointerstitial component, fibroplastic transformation of mesangioproliferative nephritis as well as the detection of mesangiocapillary, diffuse fibroplastic and extracapillary nephritis.

Adult↗

The Italian experience of the national registry of renal biopsies.

BACKGROUND: Although several registries collecting data of patients with kidney diseases exist, there are only a few registries which specifically collect data relating to renal biopsy; one such registry is the Italian Registry of Renal Biopsies (IRRB). The aim of this study was to report on the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on the histologic diagnosis during the years 1996 to 2000. METHODS: We evaluated data relating to 14607 renal biopsies, provided by 128 renal units in Italy. Data entry was performed by using the Internet-based database directly (URL http://www.irrb.net). Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS), acute nephritic syndrome (ANS). Renal diseases were divided in four major categories: (1) primary glomerulonephritides (GN); (2) secondary GN; (3) tubulointerstitial nephropathies (TIN); and (4) vascular nephropathies (VN). RESULTS: Primary GN, TIN, and VN were more frequent in males compared to females while secondary GN was more frequent in females. Diseases whose frequency was higher in males were IgA nephropathy (IgAN), benign nephroangiosclerosis (BNA), and acute tubular necrosis (ATN). A significantly higher frequency of immune-mediated secondary GN, as well as primary GN, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and mesangiocapillary GN (MCGN), was shown in females. Primary and secondary GN, TIN, and VN were more frequent in the range 15 to 65 years of age. At the time of biopsy 77% of primary GN and 61% of secondary GN presented with normal renal function. Acute renal failure (ACR) was more present in TIN (52%), while chronic renal failure (CRF) was more frequent in VN (47%). CONCLUSION: We believe collection of data relating to renal biopsies in a national registry is a useful tool for nephrologists in that it meets one of the current challenges facing the clinical research enterprise. The availability of these data will allow epidemiologic studies in health care to answer the several open questions in both prevention and treatment of renal diseases.

Adolescent↗

Detection of circulating immune complexes in patients with glomerulonephritis.

A panel of three immune complex (IC) assays was used in this study to test sera from patients with glomerulonephritis (GN): the Raji cell radioimmune assay (IRCA), the radio-labeled C1q binding assay (IC1qBA), and the microcomplement consumption test (MCT). The sensitivity and specificity of each assay was evaluated in preliminary studies, and the greater sensitivity (5 to 10microgram of aggreagated human gamma-globulin (AHG) per ml of serum) and IgG specificity of the IRCA was apparent. Problems related to the preliminary heat inactivation of test sera, the interaction of C1q with substances other than IC, and the effects of suboptimal storage of test sera were experienced with the MCT and, to a lesser extent the IC1qBA. The individual reactivities of the different assays were exploited by using them in combination. Thus ICs were detected by one or more of the assays in 87% of patients with systemic lupus erythematosus (SLE), 65% of patients with GN associated with other systemic diseases, and 39% of patients with primary GN. ICs were detected more frequently in patients with acute GN than chronic GN, and in patients with low serum C3, C4, and properdin factor B (C3PA) levels.

Acute Disease↗

[Idiopathic membranous glomerulonephritis. Clinico-morphologic relations and prognosis].

Membranous glomerulonephritis (GN) was diagnosed in 61 of 993 patients with histologically confirmed primary GN. Two-thirds of the patients were men. High hypertension was recorded in 7.5% of the patients. A typical finding was marked proteinuria (6.15 +/- 4.88 g/24 h.) with mild erythrocyturia (median 8 million in Addis sediment). At the time of biopsy 86% of the patients had normal creatininaemia, the level of which was positively correlated with the blood pressure and degree of tubulointerstitial regression. The cumulative duration of renal function in 5, 10 and 20 years was 88, 80 and 57%; during the same time intervals 22, 48 and 52% of the patients were cured.

Adult↗

Effect of sodium depletion on urinary excretion of active and inactive kallikrein in glomerulonephritic patients.

To investigate the response of urinary active and inactive kallikrein excretion to sodium depletion in golmerulonephritic (GN) patients, we measured the excretion of urinary active and inactive kallikreins in 10 primary GN patients before and after a low sodium (17 mEq/day), constant potassium (40 mEq/day) diet. They ranged in age from 24 to 47 years with 7 men and 3 women. The etiology included 4 IgA nephropathy, 4 mesangial proliferative GN, 1 minimal change disease and 1 focal sclerosis. The active urinary kallikrein activity was measured by assay of its enzymatic activity on synthetic chromogenic substrate S-2266. The urinary inactive kallikrein excretion was determined indirectly by substracting active kallikrein activity from total kallikrein activity. The latter was measured after trypsin activation of inactive kallikrein. The results showed a significant increase in total and active urinary kallikrein excretion following a low salt diet. Yet, the inactive urinary kallikrein excretion and the ratio of active/total kallikrein excretion showed no significant change. There was no correlation between active and inactive urinary kallikrein excretion either before or after a low sodium, constant potassium diet. These findings suggest that the renal kallikrein-kinin system of GN patients responds normally to the stimulation of sodium depletion.

Adult↗

Current therapeutic strategies in glomerulonephritis.

Over the past 20 years the therapy of glomerulonephritis (GN) has evolved. Today apart from steroids and cyclophosphamide, newer agents like cyclopsorine A and tracrolimus (FK 506) have been reported to achieve remission (partial or complete) in patients with nephrotic syndrome due to various GN which have failed to respond to steroids and cyclophosphamide. For those patients who do not respond to any of the primary therapeutic agents, there are now other therapies available like angiotensin II converting enzyme inhibitors, angiotensin II receptor antagonists, dipyridamole, low dose warfarin including protein restriction and therapy aimed at hypercholesterolaemia in an attempt to retard progression to end stage renal failure. This paper presents a therapeutic approach for the various forms of primary GN.

Angiotensin II↗

Strong polarization toward Th1 immune response in ANCA-associated glomerulonephritis.

AIM: Human immune response can be classified into 2 different subsets of T helper cells (Th1 and Th2) based on the pattern of cytokine production. In modern immunology, Th1/Th2 paradigm helps to explain the different inflammatory effector pathways and outcomes in human diseases. The present study was designed to determine the type of immunological response that influences anti-neutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis (GN) using cytokine analysis of peripheral T cells and diseased kidney tissues. PATIENTS AND METHODS: We analyzed peripheral blood Th1/Th2 ratio in 91 patients with primary GN, including 10 cases of ANCA-associated GN. Tissues were immunostained with markers of T cells and macrophages and osteopontin (OPN). Intrarenal expression of IFN-gamma and IL-4 mRNAs was evaluated by reverse transcriptase (RT)-PCR. RESULTS: Peripheral Th1/Th2 ratio was significantly higher in ANCA-associated GN (19.4 +/- 9.4, mean +/- SD, n = 10), than those in healthy controls (7.6 +/- 4.1, n = 27), IgA nephropathy (9.6 +/- 5.6, n = 45), membranous nephropathy (7.1 +/- 4.4, n = 13), minimal-change nephrotic syndrome (8.2 +/- 4.5, n = 13) and focal segmental glomerulosclerosis (8.3 +/- 3.9, n = 10) (p < 0.01, each). In 7 of 10 cases of ANCA-associated GN, Th1/Th2 ratio decreased significantly after treatment with corticosteroid from 21.0 +/- 12.0 to 9.0 +/- 6.6 (p < 0.05). Immunohistochemical staining showed numerous infiltrating T cells, macrophages and OPN-positive cells in both glomerular tuft and cellular crescent; OPN-positive cell distribution was similar to that of macrophages. Intrarenal expression of IFN-gamma mRNA was strongly enhanced whereas a weak expression of IL-4 mRNA was observed especially in advanced cases showing tubulointerstitial injury. CONCLUSION: Both peripheral and renal immune responses are strongly polarized toward Th1 type immune response in ANCA-associated GN. Peripheral Th1/Th2 ratio may reflect the immune responses in renal injury of ANCA-associated GN.

Adult↗

Effect of organic solvent exposure on chronic kidney disease progression: the GN-PROGRESS cohort study.

It has been suggested that solvent exposure may have a role in the progression of glomerulonephritis (GN) to ESRD, but this has never been tested with an appropriate cohort study design. A total of 338 non-ESRD patients with a first biopsy for primary GN between 1994 and 2001 were included: 194 IgA nephropathies (IgAN), 75 membranous nephropathies (MN), and 69 FSGS. ESRD, defined as an estimated GFR <15 ml/min per 1.73 m2 or dialysis, was registered during a mean follow-up period of 5 yr. Patients' lifelong solvent exposures before and after diagnosis were recorded by interview and assessed by industrial hygienist experts. Cox models were used to estimate adjusted hazard ratios (HR) of ESRD related to exposures. Overall, 15 and 14% of the patients had been exposed at a low and a high level before diagnosis, respectively. Forty-two with IgAN, 12 with MN, and 22 with FSGS reached ESRD. A graded relationship was observed for MN (age- and gender-adjusted HR [95% confidence interval] for low exposure versus none was 3.1 [0.5 to 18.2] and for high exposure versus none was 8.2 [1.9 to 34.7]) and for IgAN (1.6 [0.7 to 3.9] and 2.2 [1.0 to 4.8]) but not for FSGS. Solvent risk was mediated only partly by baseline proteinuria: Adjusted HR for high exposure versus none was 5.5 (1.3 to 23.9) for MN and 1.8 (0.8 to 3.9) for IgAN. In patients with IgAN, there was a trend in increasing HR with exposure duration before and its persistence after diagnosis. These findings support the hypothesized association of solvent exposure with the progression of GN to ESRD. They should prompt clinicians to give greater attention to patients' occupational exposures and possibly to consider professional reclassification.

Adult↗