Schistosomal glomerulopathy and changes in the distribution of histological patterns of glomerular diseases in Bahia, Brazil

Distinct patterns of glomerular lesions, including membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis, are associated with infection by Schistosoma mansoni or Schistosoma japonicum. Evidence suggests that immune complex deposition is the main mechanism underlying the different forms of schistosomal glomerulonephritis and that immune complex deposition may be intensified by portal hypertension. The relationship between focal segmental glomerulosclerosis and schistosomiasis remains poorly understood. A clinicopathologic classification of schistosomal glomerulopathies was proposed in 1992 by the African Association of Nephrology. In Brazil, mass treatment with oral medications has led to a decrease in the occurrence of schistosomal glomerulopathy. In a survey of renal biopsies performed in Salvador, Brazil, from 2003-2009, only 24 (4%) patients were identified as positive for S. mansoni infection. Among these patients, only one had the hepatosplenic form of the disease. Focal segmental glomerulosclerosis was found in seven patients and membranoproliferative glomerulonephritis was found in four patients. Although retrospective studies on the prevalence of renal diseases based on kidney biopsies may be influenced by many patient selection biases, a change in the distribution of glomerulopathies associated with nephrotic syndrome was observed along with a decline in the occurrence of severe forms of schistosomiasis.     

Histological Reassessment of Three Kidneys Originally Described by Richard Bright in 1827-36

Portions of kidney from three patients with renal disease that were originally described by Richard Bright between 1827 and 1836 have been preserved in the Gordon Museum at Guy''s Hospital. Histological study has shown that two cases fall into the current diagnostic category of mesangiocapillary (membranoproliferative) glomerulonephritis. One of these patients had a five-year clinical history and died with chronic renal failure and uraemia. The other patient died after three to four months with a severe nephrotic syndrome. The third patient was a young woman with chronic “phthisis pulmonalis” and renal amyloidosis.     

Renal leptin in experimental nephrotic syndrome

Leptin is a fat derived hormone involved in the regulation of metabolism and body composition. The kidney is the principle organ responsible for elimination of circulating leptin. Our aim is to evaluate if the nephrotic kidneys participate in the metabolism of leptin by comparing the serum leptin level in renal veins and in their renal arteries and to study the relationship between leptin and lipoprotein levels in healthy and nephrotic rats. Methods: Rats were divided into two equal groups: group 1 in which experimental nephrotic syndrome was produced by injecting them intraperitoneally with a supernatant of the homogenized mixture of their own kidney (obtained by previous unilateral nephrectomy) and complete Freund’s adjuvant. Another group constituted the control group. Leptin and lipid profile were estimated in blood samples of renal veins and renal arteries. There was a highly significant increase in leptin and lipid profile levels in the nephrotic rats compared with the normal group. There was a high significant decrease in leptin in the renal venous blood compared with its level in the renal arterial blood of normal and nephrotic rats. This work has stressed the involvement of kidney and the nephrotic renal tissue in the process of leptin metabolism and lipogenesis.     

Plasminogen activator in nephrotic syndrome

Plasminogen activators were studied in blood urine in 207 patients with nephrotic syndrome of different etiological forms. The blood plasminogen activator activity was decreased in chronic glomerulonephritis, SLE, systemic vasculities as result of great level of inhibitors (L2M), penetration of enzymes to abdominal and pleural transudates, excretion to urine. The blood plasminogen activator activity and urokinase level in chronic glomerulonephritis was dependent on the degree of nephrotic syndrome. The plasminogen activator in amyloidosis was sharply elevated because of permanent irritability of endothelial wall by amyloid mass. Venous occlusion caused the release of plasminogen activator to blood only in more favourable clinical course of nephrotic syndrome.     

Circulating soluble antigens and antibody in schistosomiasis.

Some patients with Schistosoma mansoni and S. haematobium infections were shown to have soluble schistosomal antigen in their plasma. Antibody to this antigen and to other antigens of adult worms were also present. These findings may be relevant to schistosomal-related immune-complex disease, especially the nephrotic syndrome.     

High levels of Schistosoma mansoni infections among schoolchildren in central Sudan one year after treatment with praziquantel

A longitudinal study was conducted to evaluate the impact of praziquantel (PZQ) for the treatment of Schistosoma mansoni infection among schoolchildren in Al Gunaid in Central Sudan. A cohort of schoolchildren (6-15 years of age) was investigated before and 1 year after treatment with a single dose of PZQ 40?mg/kg. Parasitological examinations for S. mansoni were performed before and after treatment, and prevalence and intensity of infection were analysed. Of 2741 schoolchildren recruited from six elementary schools at baseline, 2521 were successfully traced and re-examined at follow-up, with two complete sets of longitudinal parasitological data on S. mansoni. Boys showed significantly higher prevalence of S. mansoni infection than girls. A single dose of PZQ reduced the overall prevalence of S. mansoni infection by 36.7% (from 59.1 to 37.4%) and the intensity of infection by 41.1% (from 116.7 to 68.7 eggs per gram of stool) 1 year after treatment. The reduction in prevalence was significantly higher among the group of children with heavy infections (by 76.1%, from 6.7 to 1.6%) and among girls (by 54.1%, 42.3 to 19.4%) at 1 year after treatment. Thus, in spite of a significant reduction in the prevalence and intensity of S. mansoni infection 1 year after PZQ treatment, the prevalence of the disease was still high and further research is needed on this topic.     

儿童激素耐药型肾病综合征合并星形诺卡菌脑脓肿1例

本文报道1例激素耐药型肾病综合征儿童合并星形诺卡菌(Nocardia asteroides,N.asteroides)脑脓肿。患儿,男性,8岁,临床诊断为原发性肾病综合征(激素耐药型),病理诊断为局灶节段性肾小球硬化症(经典型)。肾穿后第4天患儿出现持续高热、抽搐,时有头痛,抗感染、抗凝治疗效果不佳。复查颅脑磁共振成像(magnetic resonance imaging,MRI)提示多发脑脓肿。头颅脓肿液经穿刺后培养显示为星形诺卡菌感染。予以多种抗生素联合糖皮质激素等治疗2个月,患儿体温正常,头痛缓解,脑脓肿范围明显缩小。因此,肾病综合征患儿在应用激素及免疫抑制剂治疗过程中如出现化脓性炎症,常规抗生素疗效差,应积极寻找病原,高度警惕诺卡菌病及其他机会性感染的可能。     

Microspectrophotometric study of the sialomucin content of the glomerular filter in the nephrotic syndrome

A microspectrophotometric study of sialomucins in human glomerular filter of the kidney in some diseases was carried out. Sialomucins were detected in paraffine sections stained after Haim, and examined on scanning microspectrophotometer. Lipid nephrosis, secondary amyloidosis, membranous-proliferative glomerulonephritis with the nephrotic syndrome were accompanied by a significant decrease in the amount of sialic acid. No reduction of sialomucins occurred in subacute glomerulonephritis with the nephrotic syndrome. A connection between the selective proteinuria and a decrease of the amount of sialomucins in the glomerulus is suggested.     

Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms

Background aimsMinimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired.MethodsThe adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time–polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry.ResultsMSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group.ConclusionsOur data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.     

Increased glomerular atrial natriuretic peptide receptor affinity in experimental nephrotic syndrome.

Atrial natriuretic peptide (ANP) is a cardiac hormone with natriuretic and diuretic effects. To better define the ANP hormonal system in the nephrotic syndrome, a condition associated with renal sodium retention, we undertook a study of glomerular ANP receptors in rats with puromycin aminonucleoside-induced nephrotic syndrome and in pair-fed controls. Nephrotic rats had significantly decreased serum albumin and total protein and significantly increased serum cholesterol, triglycerides and 24 hour urinary protein excretion. Plasma level of atrial natriuretic peptide was similar in both groups of rats. Competition binding inhibition studies in isolated glomeruli demonstrated one binding site in both groups of rats. The density of ANP binding sites in isolated glomeruli was similar in nephrotic and pair-fed rats while the binding affinity was increased significantly in the nephrotic rats. This is the first study to demonstrate alterations in renal ANP receptors in the nephrotic syndrome. Further studies will be necessary to determine whether alterations in glomerular ANP receptors contribute to renal sodium retention in the nephrotic syndrome.     

The Spectrum of Kidney Pathology in B-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma: A 25-Year Multicenter Experience

Background

Chronic lymphocytic leukemia and small lymphocytic lymphoma are 2 different presentations of the most common B-cell neoplasm in western countries (CLL/SLL). In this disease, kidney involvement is usually silent, and is rarely reported in the literature. This study provides a clinicopathological analysis of all-cause kidney disease in CLL/SLL patients.

Methods

Fifteen CLL/SLL patients with kidney biopsy were identified retrospectively. Demographic, clinical, pathological and laboratory data were assessed at biopsy, and during follow-up.

Results

At biopsy 11 patients presented impaired renal function, 7 patients nephrotic syndrome, 6 patients dysproteinemia, and 3 patients cryoglobulinemia. Kidney pathology revealed CLL/SLL-specific monoclonal infiltrate in 10 biopsies, glomerulopathy in 9 biopsies (5 membranoproliferative glomerulonephritis, 2 minimal change disease, 1 glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits, 1 AHL amyloidosis). Five patients presented interstitial granulomas attributed to CLL/SLL. After treatment of the hematological disease, improvement of renal function was observed in 7/11 patients, and remission of nephrotic syndrome in 5/7 patients. During follow-up, aggravation of the kidney disease systematically occurred in the absence of favorable response to hematological treatment.

Conclusions

A broad spectrum of kidney diseases is associated with CLL/SLL. In this setting, kidney biopsy can provide important information for diagnosis and therapeutic guidance.     

原发性肾病综合征小儿发生院内感染的危险因素分析及护理研究

目的:探讨原发性肾病综合征患儿发生院内感染的危险因素及有效的护理对策。方法:回顾性分析在我院儿科住院的原发性肾病综合征患儿的临床资料,用单因素分析与多因素非条件Logistic回归分析原发性肾病综合征(PNS)患儿发生院内感染危险因素,探究合理的护理对策对患儿疾病恢复的影响。结果:PNS患儿院内感染发生率为32(36.4%),以呼吸道感染为最常见部位18(56.3%)。PNS患儿发生院内感染组的免疫球蛋白G(Ig G)、免疫球蛋白A(Ig A)、ALB水平低于非感染组(P0.05),住院天数、24 h尿蛋白定量非感染组(P0.05)。住院天数和血清白蛋白(ALB)是院内感染独立的危险因素,其OR值(95%CI)分别为3.461(1.33~9.01)和2.215(0.87~5.63)。早期、合理的护理措施使PNS患儿疾病恢复良好。结论:住院天数长和血清白蛋白降低是并发院内感染的独立危险因素,健全院内感染控制制度、加强病房管理、完善护理措施等,可降低院内感染发生率,改善患者预后。     

Changes in renal haemodynamics in the nephrotic syndrome

It has repeatedly been found that haemodynamic changes during hypoproteinaemia in the chronic phase of the nephrotic syndrome are different from those during hypoproteinaemia in the acute phase. In our series of patients, a decrease in the filtration fraction and relative hyperperfusion of the kidneys were associated with the presence of the nephrotic syndrome. No significant changes in renal haemodynamics were observed in patients with chronic glomerulonephritis without the nephrotic syndrome or in a group of healthy volunteers. The question of whether relative hyperperfusion of the kidneys in a repeatedly relapsing nephrotic syndrome can lead to the development of focal segmental glomerulosclerosis needs to be elucidated.     

Profound urinary protein loss and acute renal failure caused by cyclooxygenase-2 inhibitor

Cumulative evidence has shown that nonsteroidal anti-inflammatory drugs (NSAIDs) can induce acute renal failure and nephrotic-range proteinuria. Cyclooxygenase-2 (COX-2) inhibitors have less nephrotoxicity; however, recent data indicate that they may cause the same renal problems as NSAIDs do. Herein, we present a case of celecoxib-associated minimal change disease (MCD) with profound urinary protein loss and acute renal failure. Renal function and nephrotic syndrome in this patient resolved completely after discontinuation of celecoxib and treatment with methylprednisolone. Clinicians should keep high index of suspicions in patients developing nephrotic syndrome and acute renal failure after taking COX-2 inhibitors since secondary MCD responds well to timely cessation of COX-2 inhibitors and administration of steroid therapy.     

Cyclophosphamide Therapy in the Nephrotic Syndrome in Childhood

Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.     

Effect of human erythropoietin (hEPO) treatment on anemia in ICR-derived glomerulonephritis (ICGN) mice.

ICR-derived glomerulonephritis (ICGN) mice are a novel inbred strain with hereditary nephrotic syndrome and are thus considered a good animal model of human idiopathic nephrotic syndrome. In the present study, we investigated the effect to erythrocyte production by human erythropoietin (hEPO) treatment in ICGN mice during the early nephrotic stage. Erythrocyte count, hemoglobin concentration and hematocrit value in hEPO-treated (5 U/body/day, for 5 days) ICGN mice were recovered to the levels found in normal ICR mice. In addition, there was no correlation between plasma creatinine level, a marker of renal function, and erythrocyte count after hEPO treatment. Therefore, anemia in ICGN mice may be caused by decreased production of EPO in the kidney following progressive parenchymal damage.     

Nephrotic Syndrome Due to Primary Renal Disease in Adults: II. A Controlled Trial of Prednisolone and Azathioprine

A controlled trial in 20 adult patients with the nephrotic syndrome due to proliferative glomerulonephritis compared the effects of consecutive eight-week courses of treatment with prednisolone in conventional dosage and a low-dose azathioprine–prednisolone combination. Though the azathioprine regimen avoided serious toxicity and produced a statistically significant improvement in creatinine clearance and urine protein excretion, the results were not significantly better than with prednisolone itself and overall were not of great clinical value. Prolongation of the azathioprine–prednisolone treatment to one year was associated with some small improvement in the results.The effectiveness of prednisolone in the nephritic syndrome of adults with minimal renal histological abnormality was confirmed by a complete loss of proteinuria within eight weeks in six out of eight patients and substantial reduction in the other two. These two patients subsequently received azathioprine as well but with equivocal results.     

Amyloidosis and familial Mediterranean fever

Familial Mediterranean Fever (F. M. F.) is an autosomal recessive disorder occurring most commonly in Sepharadi Jews and Armenians. Two phenotypic features characterize the disease: brief episodic febrile attacks of peritonitis, pleuritis or synovitis recurring from childhood or adolescence and the development of systemic amyloidosis. Attacks are accompanied by striking elevations of acute phase proteins, including serum amyloid A protein. The amyloidosis of Familial Mediterranean Fever is of the AA type, and manifest clinically as a nephropathy that passes through proteinuria, nephrotic and uremic stages to renal death. Although there is ethnic variation in the incidence of amyloidosis of F. M. F. in our patient population--predominantly Sepharadi Jews of North African extraction--an amyloidotic death at an early age is their genetic destiny. Since the introduction in 1972 of colchicine to prevent the febrile attacks, the drug has been proven and become the main stay of therapy. Today, colchicine has been shown to be effective in preventing amyloidosis as well as the febrile attacks in Familial Mediterranean Fever. End stage renal disease is not the end of the road for patients with F.M.F. because of improving outlook for dialysis and renal transplantation in these patients.     

自拟益气活血方治疗小儿脾肾气虚型肾病综合征的疗效观察

目的:探讨自拟益气活血方治疗小儿脾肾气虚型肾病综合征的临床疗效。方法:选择2014年6月到2016年10月我院收治的80例脾肾气虚型肾病综合征患儿,按随机数字表法分为对照组和治疗组各40例。对照组给予强的松治疗,治疗组在对照组治疗的基础上给予自拟益气活血方治疗,两组均治疗4个月。评估两组临床疗效,检测治疗前后两组24h尿蛋白、总胆固醇(TC)、血浆白蛋白(Alb)以及肾功能指标包括尿素氮(BUN)、血肌酐(Scr)、血肌酐清除率(Ccr)。结果:治疗组的总有效率为95.00%,明显高于对照组的67.50%,差异具有统计学意义(P0.05)。治疗后,两组24 h尿蛋白、TC、BUN及Scr水平低于治疗前,Alb、Ccr水平高于治疗前,且治疗组上述各指标水平变化均显著优于对照组,差异均具有统计学意义(P0.05)。结论:自拟益气活血方治疗小儿脾肾气虚型肾病综合征的临床疗效显著,能够明显改善患儿肾功能,值得在临床上推广应用。     

Masugi's nephritis: preparation of an active nephrotoxic serum

An active nephrotoxic serum (NTS) was prepared by immunization of rabbits with isolated renal glomeruli of rats and Freund's complete adjuvant. The glomeruli were isolated from the renal cortex by the sieving procedure. Intravenous injection of the NTS to rats induced the development of marked proteinuria and the nephrotic syndrome. Histological and electron microscopic studies of renal tissue performed by days 5 and 15 since the first injection of the NTS revealed extracapillary proliferative glomerulonephritis. IgG depositions on the basal membranes of the glomerular capillaries were linear on day 5 and granular on day 15 since the first injection of the NTS.