慢性燃煤砷污染所致肾损害的临床病理观察

目的　探讨慢性燃煤型砷污染对肾脏功能损害的临床病理学特征。方法　对 10 8例慢性砷中毒患者进行血、尿β2 -微球蛋白及肌酐、尿素氮检测 ,并对其中 5例患者进行肾脏病理学检查。结果　慢性燃煤污染型砷中毒组血肌酐、尿素氮与对照组比较差异无显著意义 (P>0 .0 5) ,而血、尿 β2 -微球蛋白 2组差异有显著意义(P <0 .0 1) ;病理学检查显示肾小球体积增大 ,毛细血管内皮细胞肿胀 ,肾间质水肿 ,系膜细胞增生 ,有少许炎性细胞浸润 ,近曲小管中度肿胀变性及脂肪变性。结论　燃用高砷煤所致砷污染可造成肾小球、肾小管功能病理性损害 ;血、尿β2 -微球蛋白是早期发现砷对肾脏损害较为敏感的临床指标     

足细胞内陷性肾小球病

57岁女性患者,临床诊断系统性红斑狼疮(SLE),抗核抗体、SSA、SSB阳性,无口干和眼干症状,少量蛋白尿是肾脏损害的临床表现,其肾功能正常。肾活检光镜组织学病变轻,仅见肾小球节段轻度系膜增生,但毛细血管袢略僵硬,免疫荧光检查阴性,超微结构观察肾小球基膜内见质膜样结构,个别足细胞胞质突入肾小球基膜,肾小球系膜区、毛细血管袢基膜内皮下及上皮侧均未见电子致密物沉积。诊断符合足细胞内陷性肾小球病。     

燃煤型砷中毒所致神经肌肉损害的临床病理观察

目的探讨燃煤型砷中毒所致神经肌肉损害的临床病理特征。方法对4例中、重度燃煤型砷中毒患者的腓肠神经与腓肠肌进行活检,光镜与电镜观察周围神经与肌肉的病理变化。结果光镜下见神经纤维变性萎缩,部分区域呈现脱髓鞘改变,间质中未见炎症细胞浸润;骨骼肌呈现节段性凝固性坏死(蜡样坏死),肌肉中未见炎症细胞浸润。电镜下见有髓神经纤维,部分有髓鞘分层、溶解塌陷,髓鞘下可见大空泡,轴浆内结构基本正常,部分血旺氏细胞轻度肿胀;肌丝灶性溶解,肌膜呈城垛样改变,T小管增多,肌细胞部分发生萎缩,间质增多。结论燃煤型砷中毒可致周围神经、肌肉病理改变,从而导致一系列临床症状,并引起功能障碍。     

燃煤型砷污染所致肺损害的临床病理观察

目的：探讨慢性燃煤型砷污染对肺损害的临床病学特征，方法：采用MD TECH活检针对10例慢性燃煤型砷中毒患者行右下肺穿刺活检术，进行肺组织病理检查，结果：所获得慢性燃煤污染型砷中毒患者肺组织外观褐红色，光镜下肺间质纤维组织增多，淋巴及中性粒细胞浸润，肺泡壁水肿，增厚，肺泡腔内含有蛋白样物质及少许尘埃细胞。电镜见肺泡Ⅱ型细胞变性，坏死，脱落，数量减少，板层颗粒变性，胶原原纤维显著性生，结论：燃用高砷煤所造成的砷污染对肺脏的影响以肺间质损害为主，表现为肺间质纤维化，临床肺功能检测表现为限制型通气功能障碍。     

先兆子痫肾病患者的临床病理及转归

目的:总结19例先兆子痫肾病患者的临床特点、肾活检病理改变特征及转归。方法:19例先兆子痫肾病患者,15例为初产妇,4例为经产妇,平均年龄23～40(28.1±4.5)岁。观察指标包括病程、临床表现、肾功能、尿液检查、肾活检病理、临床与病理联系及临床转归。结果:临床表现为高血压(100%)、蛋白尿(100%),少部分患者伴有镜下血尿(15.8%)和肾功能不全(21.1%)。肾活检组织改变表现为肾小球内皮细胞增生、肿胀(94.7%),系膜细胞增多、系膜基质增加(89.5%),周边袢弥漫或节段双轨(78.9%),肾小球局灶节段硬化(31.6%)。内皮细胞增生指数与终止妊娠时间有关,随着终止妊娠时间的延长,内皮细胞增生、肿胀逐渐消退(P<0.05)。小管间质损害较轻,但是,病理表现为局灶节段性肾小球硬化(FSGS)样损害的患者,小管间质损害较重。血管病变主要表现为小动脉透明变性(36.8%)、内皮肿胀(26.3%)、内膜增厚(26.3%)、弹力层增厚分层(26.3%),严重患者血管壁呈纤维素样坏死(5.3%)。终止妊娠后绝大部分患者,血压下降,尿蛋白减少至转阴,但病理表现FSGS、血管病变较重者尿检异常持续存在。结论:先兆子痫肾病患者临床主要表现为高血压、蛋白尿,部分患者出现镜下血尿,血肌酐升高。肾脏病理特征性表现以内皮细胞病变为主,其他表现包括系膜细胞增多、     

IgA肾病合并线粒体病

16岁女性,典型肾病综合征起病,且足量激素治疗有效.肾活检病理组织学见肾小球节段轻度系膜增生性病变,免疫荧光IgG、IgA及Clq系膜区沉积,电镜下系膜区增宽,并见系膜区电子致密物沉积,肾小球足细胞足突广泛融合,病理诊断为IgA肾病(微小病变型).2年后患者肾病综合征复发,并出现多系统损害,血白细胞基因检测示8969G＞A基因突变,符合线粒体病.尽管重切电镜标本观察到肾小管上皮细胞胞浆中异常线粒体蓄积,但不能证实肾脏疾病与线粒体相关,最终诊断为IgA肾病合并线粒体病.     

轻链足细胞病伴轻链肾小管病

老年女性患者,临床表现肾脏及血液系统为主的多系统损害,肾脏损害以中等量蛋白尿、低白蛋白血症为主要症状.肾外有轻度贫血及血小板减少,血清免疫固定电泳提示κ型IgG单克隆免疫球蛋白条带.肾活检组织学改变为肾小球足细胞及肾小管上皮细胞肿胀,胞质内见结晶样物质;免疫病理示κ轻链阳性,电镜下见菱形、圆形、梭形等多种形状的结晶,免疫胶体金技术证实上述结晶κ轻链阳性.该患者最终诊断为轻链足细胞病伴轻链肾小管病,考虑浆细胞异常增生性疾病所致.     

增生性肾小球肾炎伴晶格状结构的单克隆IgG沉积

51岁男性,病程1月,以高血压起病,肾脏损害主要表现大量蛋白尿,低白蛋白血症,伴少量镜下血尿,肾功能异常。肾外表现有轻度正细胞正色素性贫血,血清免疫固定电泳提示κ型IgG单克隆免疫球蛋白条带,骨髓活检和骨髓细胞学检查均阴性。肾活检组织学改变为肾小球系膜细胞、内皮细胞增生,毛细血管袢内较多CD68+细胞浸润,肾小球基膜内皮下大量、少量系膜区、偶见上皮侧嗜复红物沉积,沉积物免疫荧光染色仅IgG1和κ轻链阳性,电镜观察沉积物具有晶格状结构,免疫电镜证实这些晶格状的物质IgG和κ轻链阳性。该患者最终诊断为增生性肾小球肾炎伴具有晶格状结构的单克隆IgG沉积。     

肾小球固有细胞在介导局灶性和节段性肾小球硬化中的作用

各种持续的原发性或继发性肾脏损伤最终都会导致肾脏产生局灶性和节段性肾小球硬化（FSGS）的病理过程，在慢性肾脏损伤的病理过程中，FSGS的发生和发展起着关键作用。近年的研究证实：肾小球内的球内系膜细胞、脏层上皮细胞和内皮细胞等肾小球内固有细胞在介导FSGS发生和发展过程中起着重要的作用。     

遗传性C3肾炎

青年男性,5岁起病,临床表现为中至大量蛋白尿,大量镜下血尿,肾功能缓慢减退,同时补体C3水平轻度下降。有肾脏疾病家族史。肾活检光镜初始改变为肾小球系膜增生性病变,重复肾活检见肾小球不典型膜增生性病变伴内皮下、系膜区大量嗜复红物沉积,免疫荧光以C3沉积为主,Ⅳ型胶原染色正常。电镜下肾小球系膜区、内皮下大量、基膜内节段电子致密物分布。基因测序未见补体相关基因突变。最终诊断为遗传性C3肾炎。     

Microvascular disease and endothelial dysfunction in chronic kidney diseases: therapeutic implication

This paper was aimed to study biomarkers of endothelial injury in chronic kidney diseases. Fifty chronic kidney disease patients were subject to the following determinations: (i) circulating endothelial cells, (ii) soluble VCAM-1, (iii) transforming growth factor beta (TGFB), and (iv) intrarenal hemodynamics. Increased number of circulating endothelial cells was significantly observed. A significant depletion of vascular endothelial growth factor (VEGF) or a depleted VEGF/TGFB ratio was also documented. Results showed that sVCAM was not significantly different from normal control. Intrarenal hemodynamic alteration demonstrated a characteristic of hemodynamic maladjustment. Since increased number of circulating endothelial cells is a sensitive biomarker for endothelial cell injury in chronic kidney diseases, such injury is supported by the depletion of VEGF. The endothelial cell loss correlates with the glomerular endothelial dysfunction characterized by hemodynamic maladjustment at the efferent arteriole and reduction in peritubular capillary flow. In conclusion, correction of such hemodynamic maladjustment with multidrug vasodilators can effectively restore renal function in chronic kidney diseases.     

A community-based study of chronic kidney disease among type 2 diabetics in Kinmen, Taiwan

Diabetic nephropathy is the major cause of end-stage renal disease. Many studies show that chronic kidney disease can be prevented, or its progression to end-stage renal disease delayed, by effective intervention. The aim of this study was to estimate the prevalence of proteinuria and renal impairment in patients with type 2 diabetes. A community-based screening for chronic kidney disease in type 2 diabetic patients was conducted in 1999-2001. Proteinuria was defined in terms of urine protein-to-creatinine ratio. The glomerular filtration rate per 1.73m(2) body surface area was calculated using an equation from the Modification of Diet in Renal Disease Study. The overall response rate was about 78.6%. Prevalence rates of proteinuria and renal impairment were 29.4% and 15.1%, respectively. Females had higher prevalence of proteinuria and renal impairment than males. And prevalence increased with increasing age. Hypertension was associated with both proteinuria and renal impairment. Only 43.0% of patients with stages 3-5 chronic kidney disease had proteinuria. Proteinuria and renal impairment screening may identify different segments of the diabetic population. Both a glomerular filtration rate and proteinuria test are recommended as screening tools for early detection of chronic kidney disease in type 2 diabetics.     

Renal function after intravitreal administration of vascular endothelial growth factor inhibitors in patients with diabetes and chronic kidney disease

The present study aimed to determine whether intravitreal administration of vascular endothelial growth factor inhibitors is associated with deterioration of renal function, as seen with systemic administration, in patients with diabetes and chronic kidney disease. Estimated glomerular filtration rates before and after 160 intravitreal injections of vascular endothelial growth factor inhibitors (aflibercept, bevacizumab or ranibizumab) were compared in 69 patients with diabetes and with a baseline estimated glomerular filtration rate <60 mL/min/1.73 m². We also determined the incidence of acute kidney injury. The data showed no significant difference in the estimated glomerular filtration rate before and after vascular endothelial growth factor inhibitor administration in all patients and in patient subgroups based on each inhibitor. Furthermore, no episodes of acute kidney injury occurred. In conclusion, intravitreal administration of vascular endothelial growth factor inhibitors is unlikely to be associated with a deterioration of renal function in patients with diabetes and chronic kidney disease.     

Impact of diabetes on haemoglobin levels in renal disease

AIMS/HYPOTHESIS: Anaemia is a common complication of renal impairment. It has been suggested that renal failure secondary to diabetes is associated with more severe anaemia, but this has not been clearly substantiated in the published literature. To clarify this, we undertook a single centre, retrospective study to identify the impact of diabetes on anaemia associated with renal impairment. MATERIALS AND METHODS: Information on clinical, biochemical and haematological parameters of 2,052 stable ambulatory patients attending a single tertiary referral renal unit was collected. The impact of diabetic kidney disease on haemoglobin levels at all degrees of renal impairment was studied by comparison with patients with non-diabetic kidney disease after correcting for other commonly associated variables that influence anaemia in patients with renal impairment. RESULTS: Linear regression analysis showed lower haemoglobin in patients with diabetic kidney disease (p < 0.01). At chronic kidney disease (CKD) stages 3, 4 and 5, mean haemoglobin levels in patients with diabetic kidney disease compared with those in patients with non-diabetic kidney disease were 129.5 vs 136.9 g/l (p < 0.001), 120.5 vs 126.9 g/l (p < 0.001) and 107.1 vs 115.9 g/l (p < 0.01), respectively. At CKD stage 4 and 5 the two groups were comparable for ferritin, plasma intact parathyroid hormone levels, ACE inhibitor use and length of follow-up by a nephrologist. CONCLUSIONS/INTERPRETATION: Diabetic kidney disease is associated with lower haemoglobin in comparison with non-diabetic kidney disease, especially at GFR <60 ml/min.     

Dabrafenib- and trametinib-associated glomerular toxicity: A case report

Rationale:Combined treatment with dabrafenib, a B-RAF inhibitor, and trametinib, a mitogen-activated protein kinase inhibitor, is an effective option for patients with metastatic melanoma. A few cases of acute kidney injury associated with tubulointerstitial nephritis and 1 case of nephrotic syndrome have been reported in patients on this drug combination; however, progressive renal injury has not been reported. In this case study, we report a patient with metastatic melanoma who developed glomerular capillary endothelial toxicity and progressive glomerular sclerosis during combination therapy.Patient concern:Our patient was an 80-year-old woman with a history of type 2 diabetes and chronic kidney disease.Diagnosis and intervention:She was diagnosed with metastatic melanoma and commenced combination therapy with dabrafenib and trametinib.Outcomes:Her renal function progressively deteriorated; by month 20 after treatment commencement, her serum creatinine level had increased from 1.59 to 3.74 mg/dL. The first kidney biopsy revealed marked glomerular and endothelial cell damage. Her medication was stopped, but no improvement was evident. At 5 months after the first biopsy, her serum creatinine level had increased to 5.46 mg/dL; a second kidney biopsy revealed focal segmental glomerular sclerosis and marked tubulointerstitial fibrosis. She was started on hemodialysis.Lessons:We describe a patient with a metastatic melanoma who developed progressive kidney failure during treatment with dabrafenib and trametinib. The most prominent microscopy findings were glomerular endothelial damage in the initial kidney biopsy and accelerated glomerular sclerosis and tubulointerstitial fibrosis in the follow-up biopsy. We hypothesize that a decreased renal reserve and impairment of kidney repair capacity caused by inhibition of B-RAF, a downstream mediator of vascular endothelial growth factor, may explain the progressive kidney injury.     

Severe hyperparathyroidism with hypercalcemia associated with chronic renal failure at pre-dialysis stage.

We report a case of a 23-year-old Japanese woman who had severe hyperparathyroidism associated with chronic renal failure before the start of dialysis treatment. Her chief complaints were swelling and pain in both shoulders. Laboratory examination revealed renal failure (BUN 134 mg/dl, serum Cr 7.3 mg/dl), severe normocytic normochromic anemia (hemoglobin 4.3 g/dl), hypercalcemia (11.8 mg/dl), and hyperphosphatemia (9.7 mg/dl). Serum PTH levels were extremely increased (intact PTH >1,000 pg/ml: normal range 10-50 pg/ml). X-ray examination of the skull and shoulders showed a salt and pepper appearance, and cauliflower-like deformity of the distal end of both clavicles, respectively. Accelerated ectopic calcification was observed in the costal cartilages, internal carotid arteries, and splenic arteries. Ultrasonographic examination revealed enlargement of the four parathyroid glands. Thallium-technetium subtraction scintigraphy of the parathyroid glands showed increased uptake into the upper two. Renal needle biopsy revealed severe impairment of the interstitium and tubules with much milder changes in glomeruli. The etiology of the renal failure could not be identified. Hemodialysis, total parathyroidectomy and auto-transplantation into the forearm were immediately performed. The pathological diagnosis was chief cell hyperplasia of the parathyroid glands. Based on the presence of chronic renal failure, remarkable hyperphosphatemia with mild hypercalcemia, an unusually high level of serum PTH, and accelerated ectopic calcification, the patient was diagnosed to have severe secondary hyperparathyroidism caused by chronic renal failure with major impairment of the renal interstitium and tubules.     

Disturbances in renal autoregulation and the susceptibility to hypertension-induced chronic kidney disease

The risk of developing chronic kidney disease in the setting of hypertension varies among patient populations. Black hypertensive patients have an increased risk of developing hypertension-induced chronic kidney disease even after taking into account socioeconomic factors. There is evidence to suggest that the kidney is intrinsically more susceptible to the damaging effects of hypertension in black patients. This susceptibility can be traced to disturbances in the way the kidney autoregulates. Impaired renal autoregulation may be the renal manifestation of a more widespread abnormality in endothelial function. Other conditions that can impair renal autoregulation and add to the risk of chronic kidney disease include low birth weight, obesity, insulin resistance, hyperuricemia, and hypercholesterolemia. To minimize the risk of chronic kidney disease in patients with impaired renal autoregulatory capability, strict blood pressure control is required. There is indirect evidence that blocking the renin-angiotensin system may improve renal autoregulation.     

The simplified modification of diet in renal disease equation as a predictor of renal function after coronary artery bypass graft surgery

Background

After open-heart surgery, a percentage of patients have impaired renal function. This deterioration is even seen in patients with serum creatinine (s-creatinine) values that fall within the normal laboratory range, therefore s-creatinine is not an accurate reflection of renal function. Glomerular filtration rate (GFR) is a better indication of renal status. GFR can be calculated with the simplified modification of diet in renal disease (MDRD) equation – a formula that takes age, gender, race and s-creatinine level into account. The purpose of this study was to investigate the relationship between estimated GFR pre-operatively and renal impairment postoperatively.

Methods

All patients who had an isolated coronary artery bypass graft (CABG) done by one surgeon in one hospital between January 2005 and October 2007 had their s-creatinine levels determined pre-operatively. Using a computer desktop calculator, the patient’s age, gender and race were used together with the s-creatinine value to estimate the GFR. Prior to CABG, all patients were grouped into the five stages of chronic kidney disease. Renal outcome postoperatively was compared with the estimated pre-operative GFR.

Results

Nineteen per cent of the 451 patients had chronic kidney disease pre-operatively, as defined by the National Kidney Foundation, according to their estimated GFR. Twenty-three per cent of these patients had renal impairment after surgery. Of the patients with reasonable renal function pre-operatively only 4% had further deterioration of renal function. Mortality did not differ significantly, but patients with postoperative renal impairment stayed in hospital on average 2.4 days longer than those who had no renal impairment postoperatively.

Conclusions

Patients with chronic kidney disease before CABG have a six times greater chance of developing further renal impairment postoperatively than those with reasonable renal function beforehand. There is therefore a significant relationship between estimated GFR before CABG and deterioration of kidney function after surgery. The GFR, as calculated with the simplified MDRD, is a predictor of the risk of having renal dysfunction after CABG.     

慢性肾功能衰竭患者肾活检的临床意义

目的：对慢性肾功能衰竭（ＣＲＦ）患者肾活检的临床意义进行评价。方法：对２２２例临床诊断为ＣＲＦ,ＳＣｒ〉１７８μｍｏｌ／Ｌ（２ｍｇ／ｄｌ）的口才行肾活检术,分析其病理类型、标本合格率、穿刺成功率、并发症发生率及并发症的危险因素。根据肾穿后有无并发症,将患者分为并发症且和无并发症组两组,对并发症影响因素进行统计学分析。结果：肾活检后能明确诊断者占８９．１％,其中ＩｇＡ肾病、血管炎、慢性间质性肾炎、狼