Clinical Findings And Histopathological Analysis Of47Patients With Renal Amyloidosis

Objectives The renal histopathologic changes with amyloidosis comprise a spectrum. Clear relationship between the extent of amyloid deposition and the severity of clinical manifestations has not been demonstrated. Sait Sen, a pathologist in Turkey, has established a pathological type, score and, grade methods of renal amyloidosis. The incidence of renal amyloidosis and the relationship between clinical manifestations and pathologic features are not well known. The aim of the study is to investigate the incidence, the relationship of clinical manifestations and pathological features of renal amyloidosis in Chinese, to further explore the correlation between the clinical manifestations and the pathological features in patients with renal amyloidosis using a histopathologic classification, scoring, and grading methods proposed by Sait Sen.MethodsCase selection:A retrospective analysis of patients with renal amyloidosis diagnosed in our hospital from January1998to May2012. The diagnosis of renal amyloidosis is made by pathologists. The diagnosis criteria of renal amyloidosis are:HE staining showed amorphous hyalineand eosinophilic extracellular material. Silver staining showed light black homogeneous amorphous extracellular material. Congo red staining is positivity. Electron microscope showed particular ultrastructural appearance with8to10nm-diameter fibrils. Exclusion criteria:the clinical and pathological data are not intact.Clinical data:Renal amyloidosis are divided into three stages based on clinical manifestations:①proteinuria(proteinuria<3.5g/24h),②nephrotic syndrome(serum albumin<30g/L, proteinuria≥3.5g/24hy), and③renal insufficiency(serum creatinine>106umoL/L). The following clinical and laboratory variables were recorded and used for analysis:sex, age, blood pressure, microscopic hematuria, hemoglobin levels, serum albumin,24-hour urine protein excretion, blood urea nitrogen, serum creatinine, and glomerular filtration rate evaluated by MDRD.Pathological methods:For light microscopy (LM), the following stains were applied to tissue sections:hematoxylin and eosin, periodic acid-Schiff, Masson’s trichrome, Jones methenamine silver, and Congo red. For immunofluorescence, tissue sections were stained with FITC-conjugated antibodies to IgG, IgM, IgA, C3, Clq, fibrinogen, κ, λ, and SAA. Histopathological features of renal amyloidosis are standardization according to a proposed histopathologic classification, scoring, and grading system for renal amyloidosis in2010by Sait Sen. Electron microscopy (EM) was performed on47cases.Results The7975native renal biopsies were performed in our hospital from January1998to May2012. Sixty-eight patients (0.85%) were diagnosed as renal amyloidosis. Forty-seven patients with complete data entered this study. Of these,45cases were immunoglobulin light chain renal amyloidosis (AL), complicating with multiple myeloma (MM) in8cases, and2cases were amyloid A amyloidosis (AA). In45AL patients,41of patients presented with light chain of λ, and4of patients presented with light chain of κ, the ratio of them was10.3:1. The mean age of47patients was56.9±10.2years (23-76years). Thirty-three patients were male, and male to female ratio was about2.4:1.48.9%of patients were older than60ys. Twenty-four hours urine protein excretion was≥1g/24h in all patients.74.5%of patients have hypoproteinemia. Serum creatinine was higher than106umol/L in31.9%of patients. eGFR was lower than90ml/min in61.7%of patients. Hemoglobin was negatively correlated with serum creatinine (r=-0.452P=0.01). Urinary protein excretion was statistically correlated with serum albumin (r=-0.292P=0.04). Blood pressure was positively correlated with serum albumin (r=0.308P=0.008). Twenty-four hours urine protein excretion was not correlated with renal histopathologic classification, score, and grade. Immune complex deposition was associated with other glomerulonephropathy, such as IgA nephropathy (P<0.001) Histopathologic classification and grade was significantly associated (P<0.001) Clinical stages and pathological classification was statistically significantly associated (P=0.03). Clinical stages and pathological grading was significant correlated (P=0.044). The score of renal interstitial fibrosis and renal interstitial inflammatory cell infiltration was significantly difference among different clinical stage (P<0.001). Serum creatinine was higher than106umol/L in15cases, of which histopathyologic classification was type IV in6cases, type VI in7cases. Of which histopathyologic grade was grade2in8cases, grade3in7cases. In patients with renal insufficiency, the score of the amyloid deposition on the vessel wall was3or4. Histopathologic classification and grade were significantly associated with serum creatinine (r=0.295P=0.048; r=0.411P=0.004).There was no correlation between serum creatinine and the degree of interstitial amyloid deposition. There was no significant difference in AL patients complicating with MM or not.Conclusion Renal amyloidosis is an uncommon disease, accounting for less than1%in the renal biopsy. AL is the most common form of renal amyloidosis in China, with a predominant light chain type of X. Immune complex deposition was associated with other glomerulonephropathy. Urine proteinuria excretion could not show the severity of renal amyloidosis in pathology. Serum creatinine was more higher, the histopathologic classification, score and grade were more severe in patients with renal amyloidosis. The clinical stages were associated with histopathologic classification, score, and grade.