BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.
Acute-Phase Proteins/*urine ; Adult ; Biomarkers/blood/urine ; Biopsy ; Chi-Square Distribution ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology/*urine ; Humans ; Kaplan-Meier Estimate ; Kidney/*metabolism/pathology/physiopathology ; Lipocalins/*blood/*urine ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood/*urine ; Retrospective Studies ; Risk Factors ; Young Adult

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) is a well-known biomarker of acute kidney injury. We evaluated the value of plasma NGAL (pNGAL) as an independent predictor of prognosis in immunoglobulin A nephropathy (IgAN). METHODS: In total, 91 patients with biopsy-proven IgAN at a single center were evaluated. pNGAL was measured using a commercial enzyme-linked immunosorbent assay kit (R&D Systems). Adverse renal outcome was defined as chronic kidney disease (CKD) stage 3 or above at the last follow-up. Pearson correlation coefficient and Cox regression were used for analyses. RESULTS: The mean age of all patients (male:female, 48:43) was 35 years (range, 18 to 77). pNGAL ranged between 21.68 and 446.40 ng/mL (median, 123.97) and showed a correlation with age (r = 0.332, p = 0.001), creatinine (r = 0.336, p = 0.001), estimated glomerular filtration rate (r = -0.397, p < 0.001), uric acid (r = 0.289, p = 0.006), and the protein-to-creatinine ratio (r = 0.288, p = 0.006). During a mean follow-up period of 37.6 months, 11 patients (12.1%) had CKD stage 3 or above. In a multivariate Cox regression model, hypertension (hazard ratio [HR], 8.779; 95% confidence interval [CI], 1.526 to 50.496; p = 0.015), proteinuria > 1 g/day (HR, 5.184; 95% CI, 1.124 to 23.921; p = 0.035), and pNGAL (HR, 1.012; 95% CI, 1.003 to 1.022; p = 0.013) were independent predictors associated with adverse renal outcome. CONCLUSIONS: pNGAL showed strong correlations with other clinical prognostic factors and was also an independent predictor of adverse renal outcome. We suggest pNGAL as a potential predictor for prognosis in IgAN, while further studies are needed to confirm the clinical value.
Acute-Phase Proteins ; Adolescent ; Adult ; Aged ; Biomarkers/blood ; Biopsy ; Chi-Square Distribution ; Creatinine/blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications/pathology/physiopathology ; Humans ; Kidney/*metabolism/pathology/physiopathology ; Linear Models ; Lipocalins/*blood ; Male ; Middle Aged ; Multivariate Analysis ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models ; Proto-Oncogene Proteins/*blood ; Renal Insufficiency, Chronic/blood/etiology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Young Adult

PURPOSE: Behcet's disease (BD) theoretically affects all sizes and types of blood vessels and results in multi-organ involvement. However, renal BD has not been fully characterized, though the kidneys are histologically rich in blood vessels. MATERIALS AND METHODS: A total of 2007 patients who fulfilled the diagnostic criteria for BD were enrolled in this study. We reviewed the medical records and test results of the BD patients and used univariate and multivariate logistic regression analyses to determine the clinical significance of renal involvement in BD. RESULTS: Among the 2007 BD patients, we noted hematuria in 412 (20.5%) and proteinuria in 29 (1.4%). Univariate analysis showed that the BD patients with hematuria were predominantly female and older, had higher erythrocyte sedimentation rates (ESRs), and more frequently presented with genital ulcerations. BD patients with proteinuria had higher ESR levels compared to BD patients without proteinuria. In the multivariate analysis, age, sex, and ESR were found to be significantly associated with hematuria in BD patients, whereas only ESR was associated with proteinuria in BD patients. We also found that IgA nephropathy was the most common pathologic diagnosis in 12 renal BD patients who underwent renal biopsies. CONCLUSION: We suggest that routine urinalysis and serum renal function tests be performed for the early detection of renal BD, especially in older female BD patients with recurrent hematuria, high ESR levels, and frequent genital ulcers, as well as in BD patients with proteinuria and high ESR levels.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Behcet Syndrome/*complications/epidemiology/*metabolism ; Biopsy ; Female ; Glomerulonephritis, IGA/complications/diagnosis ; Hematuria/complications/diagnosis ; Humans ; Kidney/*pathology ; Kidney Diseases/*diagnosis ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Proteinuria/complications/diagnosis ; Republic of Korea ; Young Adult

No abstract available.
Aged ; Anemia/diagnosis ; Bone Marrow Cells/pathology ; Chromosomes, Human, Pair 11 ; Electrophoresis ; Glomerulonephritis, IGA/complications/*diagnosis ; Hematuria/pathology ; Hemoglobin A/analysis ; Heterozygote ; Humans ; Male ; Renal Insufficiency/diagnosis ; beta-Globins/genetics ; beta-Thalassemia/*diagnosis/etiology

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.
Acute Kidney Injury/etiology/pathology ; Antimalarials/therapeutic use ; Creatinine/blood ; Glomerulonephritis, IGA/*diagnosis/*etiology ; Hematuria/etiology ; Humans ; Immunoglobulin A/*metabolism ; Malaria/*complications/drug therapy/*pathology ; Male ; Middle Aged ; Plasmodium falciparum/*isolation & purification ; Proteinuria/etiology ; Quinine/therapeutic use

OBJECTIVETo explore the changes in the clinicopathological features of patients with IgA nephropathy with elevated uric acid level.

METHODSA total of 171 patients with IgA nephropathy diagnosed at biopsy were classified into 3 groups, namely normotensive group with normal level uric acid (group 1), normotensive group with elevated uric acid level (group 2), and hypertensive group with elevated uric acid level (group 3). The clinicopathological features were compared between the 3 groups.

RESULTSFrom group 1 to group 3, the disease duration became elongated, body weight increased, systolic and diastolic pressures elevated, blood urea nitrogen and serum creatinine increased, glomerular filtration rate decreased, and 24-h urine protein increased; the apolipoprotein A, high-density lipoprotein and albumin levels decreased, while apolipoprotein B100, triglyceride, cholesterol and low-density lipoprotein increased. The glomerular damage, tubulointerstitial lesions and arteriole hypertrophy worsened, and Lee's grade III changes were predominant in group 1, grade III or IV in group 2 and grades III-V in group 3. Mesangial proliferative glomerulonephritis was the major pathological type in groups 1 and 2, as compared with focal segmental glomerulonephritis or sclerosing glomerulonephritis in group 3.

CONCLUSIONPatients with IgA nephropathy and elevated uric acid level have greater clinicopathological damage than those with normal uric acid level, and hypertension further aggravates such damages.

Adolescent ; Adult ; Creatinine ; blood ; Female ; Glomerulonephritis, IGA ; complications ; pathology ; Humans ; Hypertension ; complications ; pathology ; Hyperuricemia ; etiology ; pathology ; Kidney ; pathology ; Male ; Middle Aged ; Young Adult

Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-alpha. The patient developed progressive, severe anemia after the use of erythropoietin-alpha. As the anemia did not improve after the administration of either other erythropoietin-alpha products or erythropoietin-beta, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-alpha at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-alpha can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.
Adult ; Anemia/drug therapy/etiology ; Antibodies/*blood/immunology ; Bone Marrow Cells/pathology ; Drug Hypersensitivity/immunology ; Erythropoietin/*analogs & derivatives/therapeutic use ; Erythropoietin, Recombinant/adverse effects/*immunology/therapeutic use ; Female ; Glomerulonephritis, IGA/complications ; Hematinics/adverse effects/immunology/*therapeutic use ; Humans ; Kidney Failure, Chronic/complications ; Oxymetholone/therapeutic use ; Red-Cell Aplasia, Pure/chemically induced/*drug therapy/immunology

Urological complications are not uncommon in Crohn's disease (CD). The most common manifestations are renal stones, enterovesical fistulas, and ureteral obstruction, but renal parenchymal disease has rarely been reported. IgA nephropathy, the most common form of primary glomerulonephritis, is usually isolated, but can be sometimes associated with chronic extrarenal disorders such as inflammatory bowel disease. We describe a case of 36 year-old man with CD associated with IgA nephropathy. He was diagnosed as CD 6 years ago and at that time, isolated proteinuria was observed. He presented recurrent proteinuria and elevation of creatinine level while he had been managed well with mesalamine and azathioprine. The renal biopsy was performed and IgA nephropathy (type IV) was diagnosed. Strict blood pressure control with angiotensin converting enzyme inhibitor and calcium channel blocker resulted in clinical improvement and normalization of serum creatinine level.
Adult ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antimetabolites/therapeutic use ; Azathioprine/therapeutic use ; Blood Pressure ; Calcium Channel Blockers/therapeutic use ; Colonoscopy ; Crohn Disease/*diagnosis/drug therapy/etiology ; Glomerulonephritis, IGA/complications/*diagnosis/pathology ; Humans ; Male ; Mesalamine/therapeutic use ; Proteinuria/diagnosis/etiology

OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.

METHODSThe renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.

RESULTSThe mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.

CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVE: To evaluate the clinical and pathological features of 94 children suffering from IgA nephropathy (IgAN) while estimating the prevalent situation in Hunan province. METHODS: To summarize the annual number of hospitalized children, those with kidney diseases, those accepted biopsy, and those confirmed as IgAN in both Xiangya Hospital and Second Xiangya Hospital undertaking kidney biopsy in Hunan province during 1995 and 2004. RESULTS: In the past 10 years, as the hospitalized population in both hospitals accrued to 9.98% each year. The rate of 7.5% was seen in those with kidney diseases. Among whom 56.3% accepted kidney biopsy and 94 of them were confirmed as IgAN. Hematuria was the main clinical presentation, seen in 71 cases, accounting to 76%, and even to 98% after excluding those with nephrotic syndrome and isolating proteinuria type of IgAN. Inflammation infiltration (91%), renal tubule degeneration (81%), and renal interstitial fibrosis (31%) were the major pathological features of 94 children, especially in nephrotic syndrome IgAN. CONCLUSION The number of children with IgAN synchronously accrues as hospitalized population, those with kidney diseases, and those by kidney biopsy. Hematuria is the major symptom. To routinely perform urine analysis and kidney biopsy in asymptomatic hematuria may improve the diagnosis. Inflammation infiltration, renal tubule degeneration, and renal interstitial fibrosis are the major pathological features in IgAN children, especially in nephrotic syndrome IgAN, probably relating to continuous proteinuria. Early control of proteinuria may delay or decrease renal tubule fibrosis.
Adolescent ; Biopsy, Needle ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Glomerulonephritis, IGA ; complications ; epidemiology ; pathology ; Hematuria ; diagnosis ; etiology ; Hospitalization ; statistics & numerical data ; Humans ; Kidney ; pathology ; Male