Yao X

Idiopathic IgA Nephropathy with Diffuse Crescent Formation

Objective: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. Methods: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. Results: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 ± 264 µmol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50–95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans’ capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 µmol/l), and only 5 were dialysis-dependent. Conclusions: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.

Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis

BackgroundPathologic studies play an important role in evaluating patients with Alport syndrome besides genotyping. Difficulties still exist in diagnosing Alport syndrome (AS), and misdiagnosis is a not-so-rare event, even in adult patient evaluated with renal biopsy.MethodsWe used nested case–control study to investigate 52 patients previously misdiagnosed and 52 patients initially diagnosed in the China Alport Syndrome Treatments and Outcomes Registry e-system.ResultsWe found mesangial proliferative glomerulonephritis (MsPGN, 26.9%) and focal and segmental glomerulosclerosis (FSGS, 19.2%) were the most common misdiagnosis. FSGS was the most frequent misdiagnosis in female X-linked AS (fXLAS) patients (34.8%), and MsPGN in male X-linked AS (mXLAS) patients (41.2%). Previous misdiagnosed mXLAS patients (13/17, 76.5%) and autosomal recessive AS (ARAS) patients (8/12, 66.7%) were corrected after a second renal biopsy. While misdiagnosed fXLAS patients (18/23, 78.3%) were corrected after a family member diagnosed (34.8%) or after rechecking electronic microscopy and/or collagen-IV alpha-chains immunofluresence study (COL-IF) (43.5%) during follow-up. With COL-IF as an additional criterion for AS diagnosis, we found that patients with less than 3 criteria reached have increased risk of misdiagnosis (3.29-fold for all misdiagnosed AS patients and 3.90-fold for fXLAS patients).ConclusionWe emphasize timely and careful study of electronic microscopy and COL-IF in pathologic evaluation of AS patients. With renal and/or skin COL-IF as additional criterion, 3 diagnosis criteria reached are the cutoff for diagnosing AS pathologically.

Detection of serum and urinary lipoprotein(a) in patients with renal diseases

SUMMARY: We measured and analysed serum and urinary lipoprotein(a) [Lp(a)] in 73 patients with various renal diseases, and 168 control subjects. the results revealed that serum Lp(a) levels were significantly elevated in patients with mesangial proliferative glomerulonephritis, membranous nephropathy, chronic renal failure and diabetic nephropathy, except patients with IgA nephropathy (IgAN) with gross haematuria. Serum Lp(a) concentrations were found to be significantly correlated with serum albumin (r=−0.5033, P<0.001) and urinary protein excretion (r= 0.3541, P<0.005), while not with serum creatinine (r=−0.0144, P >0.05). Patients with selective urinary protein excretion had a lower serum Lp(a) level than those with non‐selective urinary protein excretion. the correlation between serum albumin and serum Lp(a) levels remained significant (P<0.001) after adjustment for serum creatinine, urinary protein excretion and the selectivity of urinary protein by multivariate regression analysis. Urinary Lp(a) excretion was decreased and related to the serum creatinine level (r=−0.312, P<0.01). Our conclusion is that renal patients with proteinuria and hypoalbuminemia tend to have elevated levels of Lp(a) which are more significantly correlated to serum albumin levels than other parameters such as serum 24‐h urinary protein, selectivity of urinary protein and serum creatinine; while urinary Lp(a) excretion varies inversely with serum creatinine levels.

The clinical and pathological characteristics of Chinese patients with pauci‐immune crescentic glomerulonephritis

SUMMARY In the present study, we investigated pauci‐immune crescentic glomerulonephritis (PICGN) in Chinese patients. During 13 years (1985–98), 6400 patients underwent non‐transplanting renal biopsy in the Nanjing Jinling Hospital. Twenty‐four patients were diagnosed as having PICGN. They were 16 women and eight men with a median age of 33 (range 10–76 years). Microscopic polyarteritis (33.3%) and polyarteritis nodosa (8.3%) were the secondary diseases. The incidence of PICGN was 0.37% in renal biopsies and 22.9% in crescentic glomerulonephritis. Clinically, most patients (75.0%) showed rapidly progressive nephritis with enlarged kidneys. Onset gross haematuria was noted in 58.3% of the patients, hypertension 45.8%, nephrotic syndrome 41.7%, and oliguria 25.0%. However, systemic symptoms were rare except anaemia. Pathologically, we observed necrosis of glomerular capillaries (62.5%), infiltration of monocytes and neutrophil cells in glomeruli (66.7%), and vasculitis in interstitium (53.3%), in addition to glomerulosclerosis more than 50% (45.8%), severe tubular atrophy (83.3%) and interstitial fibrosis (75.0%). Antineutrophil cytoplasmic antibodies were positive in 52.2%. All patients except two received intensively immunosuppressive therapy. Sixteen patients were subjected to long‐term follow up (median 29.8, range 8–92 months), 12 of them had life‐sustaining renal function, four had normal range of serum creatinine (< 124 μmol/L), only four patients were dialysis dependent.