轻链沉积病肾损害的临床和病理分析

目的：了解轻链沉积病(LCDD)肾损害的临床和病理特征。方法：回顾性分析26例经临床和肾活检确诊的LCDD患者的临床和病理改变。结果：26例LCDD患者起病时的平均年龄为49.4岁(27—72岁)，其中男性21例，女性5例。8例确诊为多发性骨髓瘤(MM)，2例伴有浆细胞异常增生，另有16例病因不明。临床表现为急性肾衰3例(11．5％)，慢性肾衰17例(65．4％)，肾病综合征17例(65．4％)，15.4％的患者起病时即需行肾脏替代治疗。实验室检查发现血清和尿液游离κ、λ轻链的阳性率分别为56．5％和91．7％。肾脏病理改变以系膜结节样病变多见，占53．8％，2例表现为膜增生样病变、1例为膜性病变，中—重度小管间质慢性化病变为本组患者较特征性的病变(92．3％)。肾组织中以λ轻链沉积为主者占65．4％(17例)，κ轻链沉积占34．6％(9例)。18例患者行肾组织电子显微镜检查，均显示肾小球和(或)肾小管基膜内(外)侧不规则的纤细颗粒样电子致密物。结论：LCDD患者临床以肾功能不全伴肾病综合征多见，部分患者合并浆细胞增生性疾病。病理以系膜结节样伴严重的小管间质病变为特征。血清、尿液以游离λ轻链增高多见，肾组织中也以λ轻链沉积居多。     

Pseudo-nonsecretory multiple myeloma with light chain deposition disease

A diagnosis of nonsecretory myeloma was established in two patients with anemia and proteinuria on the basis of the suppression of polyclonal immunoglobulins and the increase of plasma cells in the bone marrow. No paraprotein was detected in the serum or concentrated urine of these patients. However, a plaque-forming assay of bone marrow cells showed the secretion of monoclonal immunoglobulin by the myeloma cells. Moreover, renal biopsies from both patients indicated the deposition of monoclonal light chains in the glomerular mesangium and basement membrane, as well as in the tubular basement membrane, a pattern consistent with light-chain deposition disease. These observations suggested that the secreted paraprotein disappeared rapidly as a result of enhanced catabolism or deposition in organs such as the kidney, producing severe proteinuria and chronic renal failure. The plaque-forming assay is a useful technique for the demonstration of this type of nonsecretory myeloma, pseudo-nonsecretory myeloma.     

Renal biopsy in elderly adults over 75 years of age

The results of 177 renal biopsies (RB) in patients over 75 years of age were analysed. The three most frequent histological types were: Overall: membranous nephritis (MN), minimal change disease (MCD) and IgA Nephropathy (IgAN); In nephrotic syndrome (51% of RB): MN (36%), MCD (33%) and amyloidosis (12%); In chronic renal failure without nephrotic syndrome (25% of RB): chronic interstitial nephritis (17%), benign nephrosclerosis (12%) and IgAN (12%); In acute or progressive renal failure (18% of RB): acute tubular necrosis (36%), crescentic GN (16%) and IgAN (12%). Isolated proteinuria was most frequently associated with IgAN. In only 40% of patients was the medical history relevant, and only in selected cases it allowed for accurate prediction of the histological findings. Our data favor a more liberal use of biopsy in the elderly patients.     

The prognosis of focal segmental glomerular sclerosis of adulthood

We describe 46 adults with idiopathic focal segmental glomerular sclerosis (FSGS). The mean age was 36.9 years (range, 15 to 80 years). Males represented 61%, and 65.2% were white. Hypertension was a presenting feature in 63% and 32.6% had microscopic hematuria. Twenty-nine patients had nephrotic proteinuria (greater than or equal to 3.0 g/24 h) at presentation, and 13 had renal insufficiency (serum creatinine concentration greater than 1.5 mg/dl). A mean follow-up of 59.8 months (range, 3 to 255 months) was obtained. In addition to segmental sclerosis, glomerular hyalinosis was observed in 65.3% of biopsies, and this was similar irrespective of the severity of proteinuria. Sixteen of the 29 patients with nephrotic proteinuria received prednisone therapy (60 mg/day) for at least 1 month. Three received cytotoxic agents in addition. A response to therapy was observed in 50%, 5 achieving a complete remission and 3 a partial remission. No patient with non-nephrotic proteinuria received prednisone therapy. The clinical course of each patient was evaluated based on the slope calculated by the linear regression method using the inverse of serum creatinine from the time of presentation to follow-up. Patients with non-nephrotic proteinuria had a better prognosis than nephrotics (P less than .05). Nephrotic patients responding to therapy had a better course than non-responders or patients not treated (P less than 0.01). At the time of last follow-up, 8 patients had progressed to end-stage renal disease, 6 of whom had presented with nephrotic proteinuria. No patient responding to therapy had progressed to end-stage renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal artery stenosis with significant proteinuria may be reversed after nephrectomy or revascularization in patients with the antiphospholipid antibody syndrome: a case series and review of the literature

Renal artery stenosis (RAS) is a disease which might present as hypertension, renal insufficiency or proteinuria and even as nephrotic syndrome. While 90% of cases are secondary to atherosclerosis, the rest of the cases are usually related to fibromuscular dysplasia. Recently, RAS has also been documented in patients with the antiphospholipid syndrome (APS). Although cases of nephrotic syndrome induced by RAS have been published, cases of patients with APS and nephrotic syndrome attributed to RAS were not reported in the literature. In this paper, three young male patients with APS, hypertension and significant proteinuria secondary to RAS are presented. The patients were treated with nephrectomy or revascularization in addition to prior treatment with warfarin, with improvement of the hypertension and the proteinuria. The relationship between renal artery stenosis, nephrotic range proteinuria and APS is reviewed. We suggest that renal artery stenosis should be included in the differential diagnosis of the nephrotic syndrome and that APS should be included in the differential diagnosis of renal artery stenosis especially in young male patients with proteinuria.     

Renal function in patients with multiple myeloma.

Renal tubular and glomerular functions were evaluated in 35 consecutive patients with multiple myeloma and were correlated with changes in renal histopathology and myeloma protein patterns. All nine patients without Bence Jones proteinuria had CCr greater than 50 ml/min. In contrast 16/26 patients with Bence Jones proteinuria had CCr less than 50 ml/min and the magnitude of the Bence Jones proteinuria correlated well with the degree of renal insufficiency. Frequent abnormalities in renal tubular acidifying and concentrating ability were observed only in patients with Bence Jones proteinuria and occurred in the absence of significant reductions of glomerular filtration rate. Severely deranged renal histology was seen only in patients with Bence Jones proteinuria and consisted primarily of tubular atrophy and degeneration; glomeruli appeared normal. These data suggest that Bence Jones proteins exert a direct nephrotoxic effect at the tubular level with resultant tubular dysfunction and tubular atrophy. Glomerular filtration rate remains relatively preserved despite the significant abnormalities of tubular function. Although obstructing tubular casts were observed only in patients with severely impaired glomerular filtration rate, many patients with similarly impaired renal function had no evidence of such casts. Instead, tubular atrophy and degeneration correlated best with renal dysfunction.     

Glomerular lesions in the acquired immunodeficiency syndrome

Between January 1982 and December 1983, 75 patients with the acquired immunodeficiency syndrome were identified in our hospitals: 35% used intravenous drugs, 50% had proteinuria in excess of 0.5 g/dL, and 10% were nephrotic. Glomerular changes seen at autopsy in 36 patients included frequent mesangial lesions and deposits associated with mild asymptomatic proteinuria. Focal and segmental glomerular sclerosis was found in 5 patients and 4 of these had the nephrotic syndrome. Whereas reversible episodes of acute renal failure were not uncommon, terminal episodes of acute renal insufficiency occurred in 14 patients. The short survival of these patients may prevent the development of chronic renal failure.     

肾病综合征合并特发性急性肾功能衰竭10例分析

１０例肾病综合征患者在病程中合并无明显诱因的急性肾功能衰竭，其临床特征均为大量蛋白尿，高度水肿，病程中突发少尿，尿渗透压降低，肾功能急骤性恶化，血肌酐及尿素氮升，高肾脏病理组织学显示肾小球无明显病变或轻微病变，但多数病人肾间质高度水肿及部分病人有肾小管上皮细胞呈灶状脱落坏死，经利尿、肾上腺皮质激素等治疗肾功能逐步恢复正常，提示肾病综合征合并特发性急性肾功能衰竭并不少见，发生率为肾功能逐步恢复正常。     

轻链沉淀病肾脏损害1例报道及文献回顾

报告了１例轻链沉淀病（ＬＣＤＤ）合并多发性骨髓瘤（ＭＭ）具有典型肾脏损害的患者。临床表现为肾病综合征、肾功能损害、异常浆细胞增生、低γ血症等。肾活检病理示肾小球系膜结节、肾小管基膜增厚、免疫酶标法抗ｋ轻链阳性。ＬＣＤＤ与异常浆细胞增生有关，多合并ＭＭ，肾脏损害为其首发和突出表现，肾功能受累明显肾脏病理有特异性的改变，免疫荧光和免疫酶标法可检出轻链的沉积，是明确诊断的重要依据。     

Durable hematological response and improvement of nephrotic syndrome on thalidomide therapy in a patient with refractory light chain deposition disease

Light chain deposition disease (LCDD) is a rare disease for which an optimal treatment is not yet available. Here, we report the clinical course of a 32-year-old woman with LCDD who was successfully treated with thalidomide. She presented with nephrotic syndrome. Based on the renal biopsy findings and the presence of monoclonal immunoglobulin light chains in her serum and urine, LCDD was diagnosed. Prednisolone and cytotoxic chemotherapy used for multiple myeloma proved ineffective. We initiated administration of thalidomide (100 mg daily) and dexamethasone (20 mg for 4 days per month). After 8 months of treatment, she achieved complete hematological remission, defined as the disappearance of monoclonal protein and a normalized free light chain ratio, which led to improvement of her renal insufficiency. She has shown sustained hematological and organ response for 31 months with thalidomide therapy. Thus, thalidomide therapy seems to be a promising approach to the treatment of LCDD.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients.

A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.     

Revisiting secondary amyloidosis for an inadequately investigated feature: dyslipidemia

Secondary amyloidosis is the most frequent form of the systemic amyloidosis around the world. Data on frequency and nature of dyslipidemia in patients with secondary amyloidosis are not conclusive. We evaluated the lipid abnormalities and their association with clinical and laboratory characteristics of the patients with secondary amyloidosis. The reports of the kidney biopsies performed in our hospital were reviewed. Clinical and laboratory data of the patients with biopsy-proven secondary amyloidosis were analyzed retrospectively. A total of 102 patients were diagnosed as having secondary amyloidosis. Familial Mediterranean fever was the leading cause of secondary amyloidosis accounting for 42.2 % of the cases. The most frequent indication for kidney biopsy was the nephrotic range proteinuria. The most common clinical and laboratory characteristics at the time of the diagnosis were edema, proteinuria and impaired renal function. The frequency of the nephrotic range proteinuria and microscopic hematuria were 75.5 and 18.6 %, respectively. Dyslipidemia was found in 88 % of the cases. Serum lipids significantly correlated with estimated glomerular filtration rate (eGFR), but not with serum albumin or urine protein levels. We demonstrated that majority of the patients with secondary amyloidosis had serum lipid abnormalities. Dyslipidemia was closely associated with GFR in a manner that patients with advanced stage kidney disease had lower serum lipid levels.     

Proteinuria: potential causes and approach to evaluation

Proteinuria may be associated with a renal or systemic disease, or it may be isolated. The latter occurs in asymptomatic patients without evidence of any disease or abnormality of the urine sediment. Isolated proteinuria may be subdivided into two broad groups: (1) benign forms, with a favorable-to-excellent prognosis and (2) persistent forms, some of which have a worrisome prognosis. Functional proteinuria may occur in disorders with altered renal hemodynamics, usually resolves, and is not associated with progressive renal disease. Idiopathic transient proteinuria is typically discovered on routine screening and usually disappears on subsequent testing. In idiopathic intermittent proteinuria, a significant number (50%) of urine samples exhibit abnormal rates of protein excretion. Although structural abnormalities may be observed on renal biopsy, progressive renal insufficiency is unusual. In orthostatic proteinuria, the rate of protein excretion completely normalizes in the recumbent position. Long-term studies show this to be a benign condition. In persistent isolated proteinuria, at least 80% of random urine samples exhibit abnormal protein excretion. This represents a heterogeneous group, but a significant proportion of these patients have prominent renal pathologic findings and progress to serious renal disease. Proteinuria with significant renal disease may be non-nephrotic or nephrotic range. The former does not exclude glomerular disease, but tubulointerstitial or vascular disorders are also likely when proteinuria is less than 2 g/24 hours. Patients with nephrotic-range proteinuria generally have a glomerular disorder. Distinction between benign and more ominous forms of proteinuria requires careful evaluation.     

Renal disease in multiple myeloma

Multiple myeloma is a malignant tumor of B (plasma) cells that is characterized by monoclonal immunoglobulin production. The incidence of myeloma is increasing worldwide, particularly among individuals of advanced age. Renal impairment at diagnosis is present in approximately 20% of patients with myeloma, and uremia is the cause of death in about 15%. Several renal disorders may be present in myeloma. Bence Jones cast nephropathy (BJCN), acute tubular necrosis, and “nonspecific” tubulointerstitial nephritis are related to nephrotoxic light chains in urine. Hypercalcemia potentiates the toxicity of urinary light chains. The tissue deposition of light chains leads to renal AL-amyloidosis or light chain deposition nephropathy (LCDN). In necropsy series, the incidence of BJCN, renal AL-amyloidosis, and LCDN is about 30%, 10%, and 4%, respectively. Clinically, urinary nephrotoxic light chain-associated disorders and LCDN are usually manifested in chronic or acute renal failure. The nephrotic syndrome is commonly due to renal AL-amyloidosis. Most cases of end-stage renal failure are due to BJCN and LCDN. The basic therapy of renal impairment is hydration, forced diuresis, and initiation of chemotherapy. Diphosphonates are effective new tools for the correction of hypercalcemia, and decrease the incidence of pathological fractures. In acute renal failure, plasma exchange in association with forced diuresis, dialysis, and chemotherapy may improve renal function. End-stage renal failure requires maintenance renal replacement therapy. In myeloma patients with advanced age, the limits of medical intervention should be judged individually. Particular attention should be paid to the supportive care of the patients.     

Membranous glomerulopathy associated with captopril therapy

Two cases of nephrotic syndrome and biopsy-proved membranous glomerulopathy (membranous glomerulonephritis) were encountered during captopril treatment of 53 hypertensive subjects in our institution. Both patients had impaired renal function before treatment and were treated with 600 mg per day. Discontinuation of captopril led to transient partial remission of proteinuria but was followed by a recurrent, fluctuating course over one year later. Repeat biopsies, eight and 12 months after discontinuation of the drug, demonstrated persistent subepithelial deposits in the glomerular basement membrane. There has been a decline in glomerular filtration rate since discontinuation of the drug, apparently due to arterionephrosclerosis. These studies suggest that glomerular basement membrane deposits in captopril-associated membranous glomerulonephritis are not readily reversible and may be associated with persistent proteinuria, contrary to some previous reports.     

CASE REPORT: Light Chain Deposition Disease of the Liver Without Renal Involvement in a Patient with Multiple Myeloma Related to Liver Failure and Rapid Fatal Outcome

We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie stage III) who developed jaundice and severe cholestasis after a first cure with systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound and CT scan showed mild hepatomegaly without evidence of extrahepatic or intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive amorphous substance. Immunohistochemistry showed positivity for kappa-light chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD immunoglobulins as well as for AA and AL proteins and for amyloid P component. A diagnosis of light chain deposition disease (LCDD) of the liver was made. The patient developed rapid deterioration of liver function, leading to a multisystem dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5% and myeloma is the underlying disease in two thirds of patients with LCDD. The kidneys are involved in almost all cases of LCDD and renal dysfunction usually reveals the disease. Only three patients with LCDD of the liver without overt renal involvement have been reported so far. This is the first observation of LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis of high tumor mass myeloma, without overt renal involvement, leading rapidly to the patient's death.     

Les atteintes rénales au cours des hémopathies malignes. Stratégie diagnostique

Kidney involvement is frequent in hematologic malignancies. It is associated with adverse outcome and treatment difficulties. It can affect every area of the renal parenchyma (tubules, interstitium, glomerulus, vessels). Various mechanisms could be implicated: deposits of immunoglobulin fractions or crystals, renal infiltration by malignant cells, urinary tract obstruction, paraneoplastic or storage glomerulopathies… Diagnostic strategy relies on the clinical presentation: acute renal failure, chronic kidney disease, glomerular proteinuria with or without nephrotic syndrome, tubular proteinuria, hydroelectrolytic disorders. In this review, we detail the diagnostic tests that are needed for the detection and the follow-up of renal involvement in hematologic malignancies, and clarify the indications of renal biopsy. We propose diagnostic strategies of renal involvement in myeloma, Waldenström's disease, high grade lymphomas and acute leukemias, low grade lymphomas and chronic leukemias. The adverse effects of treatments (chemotherapy, radiotherapy, stem cell graft …) are not addressed in this review.     

薄基底膜肾病27例研究

为了深入了解我国薄基底膜肾病的发生情况和临床、病理特点。对我院肾内科近二年来（１９９５年１月至１９９６年１０月）７２２例肾活检标本进行前瞻性研究。结果：２７例诊断为薄基底膜肾病。男７例，女２０例，平均年龄３４．６岁（１５￣５７岁），均属原发性肾小球疾病。     

A case of nephrotic syndrome associated with renovascular hypertension successfully treated with candesartan.

A sixty eight-year-old man was referred to our hospital for evaluation of hypertension and hypokalemia. His chief complaints were fatigability and weakness of the lower extremities. Atrophy of the right kidney was noted on computed tomography. The laboratory findings demonstrated massive proteinuria, markedly elevated plasma renin activity, hypokalemia, and renal insufficiency. Angiography showed total occlusion of the right renal artery. The patient was diagnosed as having nephrotic syndrome associated with renovascular hypertension. Treatment with candesartan, an angiotensin-II-receptor blocker (ARB), controlled both hypertension and proteinuria satisfactorily without worsening of his renal function. This is the first report on the effect of ARB on nephrotic syndrome associated with renovascular hypertension. Based on the results, ARB can be considered a promising agent for the treatment of patients with renovascular hypertension with massive proteinuria and renal insufficiency.     

Renal manifestations of hepatitis C infection

Hepatitis C is an important cause of renal disease, and renal complications may be the presenting manifestation of hepatitis C infection. About half of patients present with evidence of renal insufficiency, and up to one quarter present with nephrotic syndrome. Others present with proteinuria or evidence of diminished renal function. The pathogenesis of hepatitis C-associated renal disease remains incompletely defined, but most evidence suggests that glomerular injury results from deposition of circulating immune complexes in the subendothelium and mesangium. Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, is the most common renal lesion. Interferon alpha-2b is currently the treatment of choice. However, success is limited, with many patients failing to respond or suffering relapse upon discontinuation of therapy. Studies of newer treatment modalities, such as longer courses of interferon or the use of ribavirin or immunosuppressive agents, are underway. Hepatitis C-associated renal disease may progress to end-stage renal failure requiring dialysis in about 10% of patients.