Cardiac surgery in a patient with multiple myeloma combined with renal amyloidosis

We present a case of a 62-year-old woman who underwent mitral valve and aortic valve replacement owing to infective endocarditis. Previously, the patient had been diagnosed with renal amyloidosis and multiple myeloma. She underwent chemotherapy and autologous peripheral blood stem cell transplantation and has achieved nearly complete remission. The patient’s postoperative course was almost uneventful, and she was discharged on the 22nd postoperative day. This is the first case report about cardiac surgery for the patient with multiple myeloma combined with renal amyloidosis.     

肾脏淀粉样变性的临床病理分析

目的：探讨肾脏淀粉样变性病（amyloidosis,AL）的临床病理特点、诊断及鉴别诊断。方法回顾性分析9例肾脏淀粉样变性病患者的临床表现,并对其肾活检组织进行光镜、特殊染色、免疫荧光、免疫组化及超微结构观察。同时对患者进行随访获取预后信息。结果9例肾脏淀粉样变性病患者的临床上主要表现为肾病综合征伴进行性肾功能不全并逐渐恶化。肾活检组织光镜观察,早期淀粉样变光镜表现轻微,可有系膜轻度增生或基底膜空泡变性及轻度增厚,PASM染色可见节段性睫毛状结构;后期,肾小球系膜区明显增宽、基底膜增厚,毛细血管腔闭塞,呈无细胞结节硬化状态。免疫荧光表现不一,部分病例全部阴性,部分表现免疫球蛋白及补体沿系膜区或毛细血管壁不同程度的沉积。刚果红染色呈砖红色,甲基紫染色呈紫红色。免疫组化显示,5例来源于轻链λ,1例来源于轻链κ,全阴性者有3例。电镜观察下,肾小球毛细血管基底膜部分节段无明显病变,部分节段不规则增厚,肾小球基底膜外侧和（或）内皮下可见淀粉样纤维沉积;系膜轻、中度无细胞性增生,其内可见不规则排列淀粉样纤维沉积,直径8~10 nm,无分支,僵硬,排列紊乱。足突大部分融合,肾间质纤维化,其内亦可见淀粉样纤维沉积。结论肾脏淀粉样变性多见于中老年,根据光镜的典型病理学改变,并结合刚果红和甲基紫染色,可明确诊断。电镜检查是早期诊断肾淀粉样变的重要手段。     

Perimembranous-type renal amyloidosis: a peculiar form of AL amyloidosis

Six cases of perimembranous-type renal amyloidosis were reported. This type of renal amyloidosis was characterized by amyloid deposition predominantly involving the epithelial aspect of the glomerular capillary wall. Florid spicular arrangement was another representative feature. This type of amyloid deposition was found in 8% of autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations. autopsy cases of systemic amyloidosis. All cases were categorized as AL amyloidosis and developed the nephrotic syndrome irrespective of the amount of amyloid within the glomeruli. The results obtained suggest that perimembranous-type renal amyloidosis is a peculiar form of AL amyloidosis both in morphology and clinical manifestations.     

AL amyloidosis with renal involvement

Primary (AL amyloidosis) is a systemic disease characterized by an amyloid deposition process in many organs, with unsatisfactory survival of patients. The monoclonal light chains form the fibrils that deposit and accumulate in tissues. Renal involvement is very frequent in AL amyloidosis and could lead to development of nephrotic syndrome followed by the renal failure in many cases. Classic therapeutic combination melphalan and prednisone has been supplemented with drugs with different mechanisms of action in this group of patients: high-dose dexamethasone, high-dose dexamethasone with melphalan, combination of vincristine, doxorubicin, and dexamethasone or newly high-dose melphalan supported by peripheral blood stem cell transplantation. This progressive therapy leads to the better survival and prognosis in the majority of patients. Alternative therapeutic approaches include thalidomide (alone or in combination with cyclophosphamide), lenalidomide, iododoxorubicin, etanercept and rituximab. The development of immunotherapy is expected in the near future.     

New advances in renal amyloidosis

Renal amyloidosis is a rare and intractable disease that accounts for 0.2% of the original kidney diseases of dialysis patients in Japan. However, the number of patients with renal amyloidosis seems to be increasing in recent years. There have been some new concepts focusing on the mechanism of amyloidogenesis, such as molecular chaperones, seeding mechanism, and genetic polymorphisms of precursor protein. Clinical and histological features of renal amyloidosis vary according to the type. Significantly higher levels of urinary protein excretion are seen in the AL type, whereas microscopic haematuria is more prominent in the AA type. Histologically, amyloid deposition of AL type has stronger predilection for GBM than mesangium, and spicule formation is more frequently observed. In contrast, AA type has a higher affinity to TBM and interstitial area. For the histological diagnosis of renal amyloidosis, plural staining methods including Congo-red, Daylon and thioflavin-T stains are available. Combinations of these staining methods are necessary for establishing the precise diagnosis. The more recent and intensive treatments for renal amyloidosis are expected to improve patient outcome. For AL amyloidosis, high-dose melphalan plus high-dose dexamethasone or VAD, in conjunction with bone marrow stem cells transplantation, have shown a definitive effect on reducing urinary protein excretion. The biological agent, tumor necrosis factor (TNFα) blocker, improves the renal function in AA-type renal amyloidosis, as well as suppresses the inflammatory reactions in patients with rheumatoid arthritis. Clinical advances have been made in various aspects of renal amyloidosis.     

Dialysis-related amyloidosis after renal transplantation

There is no effective therapy for dialysis-related amyloidosis (DRA). The restoration of renal function with a functional graft seems the most reasonable therapy for this disturbing disease. Although there are not many prospective series on the efficacy of renal transplantation for DRA, all the studies agree that most of the patients experienced a significantly clinical improvement of the articular symptoms after a successful renal transplantation. Nevertheless, radiologic (bone cysts) and histologic lesions did not disappear after long-term follow-up.     

Gelsolin肾淀粉样变性一例

钙结合微丝蛋白(gelsolin)淀粉样变性是一种罕见的家族遗传性淀粉样变。我们报道1例gelsolin肾淀粉样变性,53岁男性,蛋白尿十余年,临床表现中等量蛋白尿,肾功能正常。肾组织光镜提示刚果红染色阳性,同时免疫病理阴性,gelsolin阳性,基因测序结果为gelsolin基因NM_000177.4:c.640G>A杂合突变,提示芬兰型gelsolin淀粉样变性。该患者最终诊断为gelsolin肾淀粉样变性,系国内首次报道。     

Primary amyloidosis of renal pelvis and renal cortical adenoma

A case of primary renal pelvic amyloidosis presenting with spontaneous extravasation is discussed. The association with an ipsilateral renal cortical adenoma is noted. A review of the pertinent literature is given.     

Influence of renal dysfunction on mortality after cardiac surgery: modifying effect of preoperative renal function

BACKGROUND: Acute renal failure (ARF) requiring dialysis is an independent risk factor of mortality after cardiac surgery; the level of preoperative renal function influences the risk of both postoperative ARF and mortality. The relationship between mild renal dysfunction and mortality, and the modifying effect of baseline renal function on this association, is less clear. METHODS: We studied 31,677 patients undergoing cardiac surgery between 1993 and 2002. We used a logistic regression model to assess the relationship between postoperative renal dysfunction and mortality, while adjusting for preoperative renal function, postoperative ARF requiring dialysis, and other risk factors. RESULTS: The overall postoperative mortality rate was 2.2% (698/31,677). For the entire cohort, a clinically relevant increase in the adjusted risk of mortality occurred beyond 30% decline in postoperative GFR. The mortality rate was 5.9% (N, 292/4986) among patients who developed 30% or greater decline in postoperative GFR not requiring dialysis versus 0.4% (N, 106/26,136) among those with <30% decline (P < 0.001). A significant interaction between preoperative GFR and percent change in postoperative GFR (P < 0.001) indicated that at equivalent degrees of renal dysfunction, the mortality risk was greater at a lower preoperative GFR. ARF requiring dialysis was strongly associated with mortality in the model (odds ratio 4.2; 95% CI 3.1-5.7). CONCLUSION: Renal dysfunction not requiring dialysis is an independent risk factor of mortality after cardiac surgery. A better preoperative GFR attenuates the effect of postoperative renal dysfunction on mortality; this interaction needs to be considered while defining a clinically relevant threshold of ARF.     

Juvenile rheumatoid arthritis and renal amyloidosis

Clinical renal abnormalities, including haematuria, proteinuria, abnormal urinary sediment, decreased renal functions and hypertension are relatively common in children with juvenile rheumatoid arthritis (JRA). These findings may be due to renal amyloidosis or administration of drugs that are potentially nephrotoxic. The case of an 11 years old boy diagnosed as JRA at 4.5 months of age and treated with steroids for 10 years is presented. In his history he had hypertension for 5 years and cataract for one year. Renal biopsy was done to evaluate the aetiology for proteinuria, which was overlooked before his admission to our Department. Secondary renal amyloidosis due to JRA was found at biopsy. The importance of investigation for amyloidosis during the long-term follow-up of JRA is reemphasized.     

Hereditary systemic amyloidosis with renal involvement

Hereditary systemic amyloidosis is caused by deposition of genetically variant proteins as amyloid fibrils. The types that present with renal disease are usually associated with mutations in the genes for either apolipoprotein AI, apolipoprotein AII, lysozyme or fibrinogen A alpha-chain. These diseases are inherited in an autosomal dominant manner with variable penetrance, and can present clinically at any time from the teen years to old age, though usually in mid-adult life. Hereditary amyloidosis is uncommon, but its precise characterization has major implications for patient management and genetic counseling, and it has been an extremely valuable model for elucidating the pathogenesis of amyloid deposition generally. The amyloidogenic variant proteins associated with hereditary amyloidosis are less stable than their normal wild type counterparts and even under physiological conditions can populate partly unfolded states, involving loss of tertiary or higher order structure, which readily aggregate with retention of beta-sheet secondary structure into protofilaments and fibrils. The clinical phenotype of hereditary renal amyloid is non-specific and is readily misdiagnosed as acquired AL amyloidosis. Indeed, we have lately demonstrated that five percent of patients with apparent sporadic amyloid have hereditary fibrinogen A alpha-chain amyloidosis associated with the valine 526 variant. Penetrance of this particular mutation is extremely low in most families obscuring the genetic etiology, but the renal histology is very characteristic showing substantial accumulation of amyloid within enlarged glomeruli, but none in blood vessels or the interstitium. DNA analysis is now performed routinely in UK National Amyloidosis Centre in patients with systemic amyloidosis in whom AA or AL fibril type cannot be definitively verified.     

Subclinical adrenocortical insufficiency in renal amyloidosis

In order to investigate the functional significance of possible adrenal amyloid infiltration in patients with renal amyloidosis, we performed corticotrophin stimulation tests in 15 patients having renal amyloidosis with no clinical evidence of adrenocortical insufficiency and 12 controls. In 7 of the patients, the cortisol increments obtained during the test were found to be consistent with primary adrenal insufficiency due to possible amyloid infiltration of the adrenal cortex; in contrast, in all control subjects, adrenal responses to the test were regarded as sufficient for proper adrenal function.     

肾淀粉样变的临床与病理分析

现总结经我院确诊的10例肾淀粉样变患者的资料，由此探讨肾淀粉样变的临床、病理特点及预后。 一、对象与方法 2003年1月至2005年12月在我院肾内科接受肾活检998例患者，经HE、刚果红染色及电镜观察等病理学检查，10例确诊为肾淀粉样变。     

Improved outcome of renal transplantation in amyloidosis

Abstract We report our results in 96 patients with amyloidosis who received 105 cadaveric renal allografts. The graft survival of amyloidosis patients has improved with time and with improved immunosuppression. The graft survival of amyloidosis patients is comparable to the results in another systemic disease, i.e., diabetes,     

The course of renal amyloidosis with uraemia

The course of uraemia in 47 patients with renal amyloidosis has been studied. The median survival with a S-creatinine of 150 μmol/l was approximately 18 months, but 15% survived for more than 3 years. Deterioration arose often suddenly and was of unclear cause. Approximately 25% of the patients improved for a while and the reason for this temporary improvement is also unclear. The unsteady course during the uraemia period for amyloidosis patients makes prognosis calculations very much less accurate than for patients with cystic kidneys.     

Long-term effects of losartan on proteinuria and renal function in patients with renal amyloidosis

OBJECTIVE: To investigate the effect of the angiotensin II receptor antagonist losartan on proteinuria in secondary amyloidosis cases. MATERIAL AND METHODS: Sixteen patients with renal biopsy-proven AA amyloidosis with proteinuria were included in the study. All the patients had received colchicine treatment for at least 18 months. The patients were divided into two groups with similar age and gender distributions. Eight patients were given losartan at a dose of 50 mg/day for 12 months and the other 8 patients served as controls. Mean arterial blood pressure, proteinuria, serum albumin level and renal function were determined at the initiation of the study and after 1 and 12 months. RESULTS: There were no significant differences in proteinuria, serum albumin level, renal function or mean arterial blood pressure at the initiation of the study. In the losartan group daily proteinuria decreased significantly from 5.2 +/- 0.7 g at the initiation of the study to 3.9 +/- 1.2 g at 1 month and 3.6 +/- 0.8 g at 12 months, while in the control group it changed from 4.6 +/- 1.0 g to 4.7 +/- 1.0 g and 6.1 +/- 1.2 g, respectively. The increment at 12 months was significant. After 12 months of treatment with losartan, proteinuria was significantly lower in comparison to the degree of proteinuria in the control group. Serum albumin level increased significantly in the losartan group but was unchanged in the control group. In the control group, creatinine clearance showed a significant decrease. There was no significant difference in mean arterial blood pressure measurements, serum creatinine levels, total protein, albumin and creatinine clearance levels between the two groups. CONCLUSIONS: Losartan seemed to prevent an increase in proteinuria without altering the creatinine clearance level in patients with amyloidosis type AA during a 12-month period. This indicates that losartan may be used to decrease proteinuria in this patient group. However, our results are only preliminary and need to be confirmed by larger studies.