Membranoproliferative Glomerulonephritis and Persistent Hypocomplementaemia

The clinical, laboratory, and histological findings of 50 patients with membranoproliferative glomerulonephritis are described. Three-quarters of the patients, who were mostly older children and young adults, presented clinically with a mixture of “nephritic” and “nephrotic” symptoms; the remaining quarter had no symptoms and were diagnosed after the discovery of proteinuria and microscopic haematuria.Though this clinical picture may occur in other forms of glomerulonephritis, the patients described here were unified as a group by their glomerular morphological appearance—namely, a combination of mesangial proliferation and capillary wall thickening, mainly due to subendothelial accumulations of mesangial matrix.In 68% serum C3 (β10-globulin) levels were reduced initially, while a further 16% subsequently showed a fall to abnormally low levels. All patients had substantial proteinuria, usually of moderately impaired selectivity, and all but one had haematuria in addition. Children frequently presented with an illness resembling acute nephritis, whereas adults usually had a nephrotic syndrome from the start.In 31 patients, followed for periods of one to eight and a half years, serial measurements of glomerular filtration rate were made. Sixteen have experienced no deterioration of renal function, though their proteinuria continues unchanged. Fifteen have shown progressive deterioration; six of them are still well, six are on regular dialysis treatment, and three have died. Treatment with corticosteroids, azathioprine, or cyclophosphamide, alone or in combination, did not seem to influence the course of the disease, and another two patients died from complications of steroid therapy. The disease usually runs a chronic course and appears to be progressive.     

Natural course of penicillamine nephropathy: a long term study of 33 patients

To elucidate the natural course of the nephropathy associated with penicillamine and thereby facilitate its clinical management 33 patients with rheumatoid arthritis who developed proteinuria during treatment with oral penicillamine were studied in detail throughout their renal illness. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 74 months (range 16-148 months). Fourteen patients developed proteinuria within six months after the start of treatment and 27 within 12 months. When treatment was stopped the proteinuria reached a median peak of 4·2 g/24 h (range 0·3-15·0 g/24 h) at one month (range 0-7 months) before resolving spontaneously by six months (12 patients), 12 months (21), or 18 months (29). In all patients but one, who developed carcinoma of the renal pelvis, proteinuria resolved by 21 months and its median duration was eight months. The median first and last measurements of creatinine clearance showed no appreciable change (80 ml/min and 78 ml/min), and no patient died from or needed treatment for renal failure. The HLA-B8 or HLA-DR3 alloantigen, or both, were identified in 10 patients. Renal biopsy specimens showed membranous glomerulonephritis in 29 patients, minimal change nephropathy in two, and electron dense deposits in the mesangial regions in two.In all the patients whose nephropathy was due solely to treatment with penicillamine the proteinuria resolved completely when the drug was withdrawn; renal function did not deteriorate, and corticosteroids were unnecessary.     

Canada's medical schools

A 20-year-old man with a 10-year history of glomerulonephritis presented with a purpuric rash on his legs. A renal biopsy specimen obtained when he was 11 years old had shown mesangial glomerulonephritis; staining 9 years later for IgA had negative results. A second renal biopsy, performed when the rash was present, revealed mesangial glomerulonephritis and mesangial deposits of IgA; biopsies of the involved skin showed leukocytoclastic vasculitis. In this case isolated glomerulonephritis appeared to change to a multisystem illness, with a different immunologic character, through one of several possible pathogenetic mechanisms.     

Recurrent haematuria: role of renal biopsy and investigative morbidity.

The usefulness of renal biopsy in investigating unexplained haematuria was assessed by a study of 33 adults referred consecutively with this syndrome. Unequivocal abnormalities were seen on light microscopy or immunofluorescence in 31 of the 33 specimens of renal tissue examined. In 18 patients deposits of IgA were present in the mesangium. Loin pain occurred in only two of the 18 patients with mesangial IgA deposits, compared with 11 of the 15 patients without these deposits. Seven of the nine women in this series had had loin pain compared with only six of the 24 men. Thus a woman with loin pain and haematuria was not likely to have mesangial IgA nephropathy but this was found in 14 of the 18 men with unexplained painless haematuria. Failure to appreciate the role of renal biopsy in the investigation of unexplained haematuria may result in unnecessary radiology, considerable morbidity, and even in unjustified nephrectomy.     

Isolated glomerulonephritis with mesangial IgA deposits.

Mesangial deposits of IgA, occurring in the absence of systemic disease known to be associated with nephritis, were detected by immunofluorescence microscopy in renal biopsy specimens from 25 patients (4% of 630 specimens studied). Associated deposits of C3 were always present, usually with IgG, but IgM deposits were less common and C1q was never seen. On light microscopy most of the biopsy specimens showed mesangial of focal nuclear proliferation though some were normal. Fifteen of the 25 patients presented with macroscopic haematuria, which was usually recurrent and preceded by a sore throat, whereas the remaining, and usually older, patients presented with persistent proteinuria and were more likely to have impaired renal function. This incidence of "mesangial IgA disease" is less than that reported by French workers. There was a significantly high incidence of familial renal disease among these patients. No abnormalities of serum complement or IgA concentration were found.     

亲属活体供肾的病理改变及其临床相关性

目的 探讨亲属活体供肾的病理改变与类型,分析供肾病理改变与供体临床预后的相关性.方法 2007 年5 月至2008 年7 月完成59 例亲属活体供肾肾移植,供肾灌注后用Trucut 肾活检针(18 G)行肾下极穿刺活检,常规行光镜检查和免疫组化检查.供体术后观察血清肌酐、尿常规和尿生化等.结果 55 岁以下供者肾脏出现...     

Glomerular lesions in HIV-infected patients: a Yale University Department of Medicine Residency Peer-Teaching Conference.

HIV-associated nephropathy (HIVAN) is a clinicopathologic entity characterized by heavy proteinuria, absence of edema and an irreversible decline in renal function. Findings on renal biopsy include: collapsed glomerular capillaries; visceral glomerular epitheliosis; microcystic tubules; mesangial prominence; and endothelial tubuloreticular inclusions. Early in the AIDS epidemic, HIVAN was the predominant glomerular lesion observed in HIV-infected patients. It is being increasingly recognized, especially in Caucasian populations, that a variety of immune complex-mediated lesions such as membranoproliferative glomerulonephritis, proliferative glomerulonephritis and IgA nephropathy are associated with HIV infection. In this review we present two cases: one patient whose first presentation of AIDS was end-stage renal disease, who on biopsy was found to have HIVAN, and the second, who was infected with HIV, and on biopsy was found to have hepatitis C-related hepatitis C related membranoproliferative glomerulonephritis. We also review the current literature on HIVAN and HIV-associated immune complex diseases (HIVICDs). Each case illustrates an important clinical point. The first that renal disease can be the first manifestation of HIV infection and the second that HIV-infected patients may develop immune complex related renal diseases, some of which may be potentially treatable.     

Hereditary Nephropathy with Hematuria (Alport's Syndrome)

Among 82 members and four generations of a French-Canadian family, 14 cases of hereditary nephropathy (Alport''s syndrome) were documented. Five additional members of the family had died, probably because of this same illness. Deafness occurred in five family members with nephropathy and in one without renal disease. Ten of 12 affected males died in uremia before they had reached the age of 40 years. One of seven affected females died following a pregnancy. In two surviving patients, special investigations failed to elicit intrinsic tubular defects such as amino-aciduria, renal tubular acidosis, hyperphosphaturia or renal glucosuria. Systemic illness such as abnormal aminoacids in serum, primary hyperoxaluria, diabetes mellitus and infections were also excluded. Immunological defects were not demonstrable and the staining of renal biopsy tissue with fluorescein-labelled anti-β₁c, anti-IgG and antifibrinogen was negative. Renal tissue material of early, advanced and terminal hereditary nephropathy showed both tubular and interstitial, vascular and glomerular lesions. Electronmicroscopy showed marked thickening of tubular and glomerular basement membranes, increase of mesangial tissue and fusion of foot processes but failed to demonstrate “immune deposits.” It is postulated therefore that hereditary nephropathy results from an inborn error of metabolism where an as yet unidentified metabolite damages the renal tissue as well as the acoustic nerve, analogous perhaps to the action of certain drugs, e.g. nephro-ototoxic antibiotics.     

Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy

Aims

To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin''s lymphoma (NHL) by renal biopsy.

Methods

The clinical features and histological findings at the time of the renal biopsy were assessed for each patient.

Results

We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients.

Conclusion

A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.     

Controlled Trial of Prednisone in Adult Patients with the Nephrotic Syndrome

A multi-centre controlled trial of steroid treatment of the nephrotic syndrome was carried out on 125 patients. Of these, 64 were controls and 61 received prednisone in a recommended dose range of 20-30 mg./24 hours. The actual initial dose averaged 29 mg./24 hours. Treatment was continued for a variable period, but not less than six months. More than 10 mg./24 hours was given on average for 12 months to all patients, and for longer periods to some. Patients were classified, on the basis of biopsy specimens, into three groups: A, minimal change; B, membranous nephropathy; and C, proliferative glomerulonephritis. In groups B and C prednisone did not have any strikingly favourable effect on proteinuria or on renal function as compared with the control group. In group A, however, prednisone reduced proteinuria to a striking and statistically significant extent. It had little if any effect on long-term renal function in any group. The death rate was higher in the combined prednisone groups (17/61) than in the control groups (12/64). This difference was not statistically significant, but there was a significantly higher number of deaths from cardiovascular disease in the prednisone group, whereas the numbers of deaths from renal failure were not significantly different in the two groups.     

Haematuria Increases Progression of Advanced Proteinuric Kidney Disease

Background

Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function.

Objective

To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up.

Results

The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73m2/year, p<0.05), but not in patients >65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025).

Conclusions

The presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatment.     

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

Anti-Thy1 glomerulonephritis is a rat nephritis model closely simulating human mesangial proliferative glomerulonephritis. It affects primarily the mesangium, yet displays substantial proteinuria during the course. This study investigated the molecular signals underlying proteinuria in this disease and the modulation of which by the known antiproteinuric agent, pentoxifylline. Male Wistar rats were randomly divided into a control group and nephritic groups with or without treatment with IMD-0354 (an IκB kinase inhibitor), SB431542 (an activin receptor–like kinase inhibitor) or pentoxifylline. Kidney sections were prepared for histological examinations. Glomeruli were isolated for mRNA and protein analysis. Urine samples were collected for protein and nephrin quantitation. One day after nephritis induction, proteinuria developed together with ultrastructural changes of the podocyte and downregulation of podocyte mRNA and protein expression. These were associated with upregulation of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β/activins mRNAs and activation of nuclear factor (NF)-κB p65 and Smad2/3. IMD-0354 attenuated proteinuria on d 1, whereas SB431542 decreased proteinuria on d 3 and 5, in association with partial restoration of downregulated podocyte mRNA and protein expression. Pentoxifylline attenuated proteinuria and nephrinuria through the course, plus inhibition of p-NF-κB p65 (d 1) and p-Smad2/3 (d 5) and partial reversal of downregulated podocyte mRNA and protein. Our data show that the pathogenesis of proteinuria in anti-Thy1 glomerulonephritis involves TNF-α and TGF-β/activin pathways, and the evolution of this process can be attenuated by pentoxifylline via downregulation of NF-κB and Smad signals and restoration of the podocyte component of the glomerular filtration barrier.     

The natural course of gold nephropathy: long term study of 21 patients.

To clarify the natural course of gold nephropathy and thereby facilitate its clinical management 21 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular sodium aurothiomalate were studied in detail throughout their renal illnesses. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 60 months (range 16-130 months). Ten patients developed proteinuria after six months'' treatment, 15 after 12 months, and 18 after 24 months. When treatment was stopped the proteinuria reached a median peak of 2.1 g/day (range 0.7-30.7 g/day) at two months (range 1-13 months) before resolving spontaneously, in eight patients by six months, in 13 by 12 months, and in 18 by 24 months. All patients were free of proteinuria by 39 months, the median duration being 11 months. The median first and last measurements of creatinine clearance showed no significant change (77 ml/minute and 59 ml/minute, respectively), and no patient died from or needed treatment for renal failure. HLA-B8 or DR3 alloantigens, or both, were identified in seven patients. Renal biopsy specimens showed membranous glomerulonephritis in 15 patients, a minimal change nephropathy in two, mesangial electron dense deposits in two, and no appreciable glomerular changes in two. In these 21 patients the proteinuria of gold nephropathy resolved completely when treatment was withdrawn. Renal function did not deteriorate, corticosteroids were unnecessary, and several different renal lesions were seen.     

Localization in situ of type VI collagen protein and its mRNA in mesangial proliferative glomerulonephritis using renal biopsy sections

 Extracellular matrix accumulation is crucial in the pathogenesis of glomerulosclerosis in mesangial proliferative glomerulonephritis (GN). In an attempt to explore the distribution of type VI collagen and its synthesizing cells in normal and diseased glomeruli, we investigated mRNA and protein expression of type VI collagen in renal biopsy sections, histologically diagnosed as mesangial proliferative GN. Five renal biopsies from patients diagnosed as having minor glomerular abnormalities and one surgical renal tissue were also simultaneously examined as controls. Immunohistochemical studies revealed type VI collagen immunostaining in the mesangium and glomerular basement membrane of the control glomeruli. Compared to the control, increased deposition of type VI collagen was noted in the mesangial proliferative and sclerotic lesions in GN. To identify the cells responsible for the synthesis of type VI collagen mRNA, renal sections were hybridized in situ with digoxigenin-labeled antisense oligo-DNA probe complementary to a part of α1 (VI) mRNA. Occasionally intraglomerular cells hybridized with digoxigenin-labeled antisense pro α1 (VI) oligo-DNA in control glomeruli. An increased number of intraglomerular cells (mostly epithelial cells) were, however, positive for α1 (VI) mRNA expression in GN sections. The present study documents the distribution of type VI collagen in the normal glomeruli and provides further evidence of accelerated synthesis of this collagen in mesangial proliferative GN. Accepted: 21 July 1998     

糖尿病肾病合并非糖尿病肾病的临床病理分析

目的：分析糖尿病肾病合并非糖尿病肾病的临床病理特点。方法：选取我院肾内科收治的临床诊断为糖尿病肾病的患者56 例,肾脏穿刺进行肾脏活体组织检查,通过病理诊断将患者分为两组,分别为糖尿病肾病组和糖尿病肾病合并非糖尿病肾病组, 比较两组患者的糖尿病病程、糖化血红蛋白、血压、血肌酐、血尿素氮、血尿酸、血清白蛋白、尿蛋白定量、血尿、视网膜病变。结果： 经肾脏组织活检,56例患者中NDRD 患者24 例(42.9%),DN患者32 例(57.1%);对24 例NDRD患者进行病理类型分类,其中IgA 肾病33.0%,膜性肾病25.0%、系膜增生性肾小球肾炎20.2%、高血压肾损害8.3%、微小病变4.2%、局灶节段硬化性肾炎4.2%、新 月体性肾小球肾炎4.2%。与DN组比较,NDRD 组糖尿病病程、糖化血红蛋白、血尿、视网膜病变均有差异(P＜0.05);而血肌酐、血 尿素氮、血尿酸、血清白蛋白、尿蛋白定量均无明显差异(P＞0.05)。结论：临床诊断的糖尿病肾病患者中有很大一部分实际上为糖 尿病肾病合并非糖尿病肾病,且以IgA 型肾病比较多见,糖尿病病程、糖化血红蛋白、血尿、视网膜病变对鉴别二者具有一定的指 导意义。     

应用高脂饮食联合维生素D3建立慢性系膜增殖性肾炎血管病变大鼠模型

目的 探讨应用高脂饮食建立慢性系膜增殖性肾炎血管病变模型的方法.方法 雄性Wistar大鼠行单侧肾切除后随机分为单纯肾切除组、单纯肾炎组、单纯高脂组、肾炎高脂组.单纯肾炎组、肾炎高脂组在单侧肾切除后3d尾静脉注射OX7抗体(100 mg/kg),1周后尾静脉连续注射OX7抗体(每次100 mg/kg,1次/周,共3次),单纯肾切除组和单纯高脂组在同一时间尾静脉注射PBS,注射抗体后第2天单纯高脂组、肾炎高脂组腹腔注射维生素D3(6万U/kg,1次/4周),同时给予高脂饲料.分别于第4、8、10周观察各组大鼠的一般情况、体重、血压、尿蛋白、血浆白蛋白、血脂、血钙、肾功能以及肾脏病理改变.结果 模型组(肾炎高脂组)大鼠第8周肾小球外的小动脉出现管壁增厚,管腔变小,平滑肌细胞减少,细胞排列紊乱,纤维组织增生.第10周单纯肾炎组和单纯高脂组肾小球外小动脉管壁轻度增厚,管腔变化不明显,模型组血管病变积分明显高于单纯肾炎组和单纯高脂组(P＜0.05).结论 通过对慢性抗Thy1肾炎大鼠加用高脂饲料并腹腔注射维生素D3的方法,可以成功建立慢性系膜增殖性肾炎血管病变模型.     

Effect of Proteinuria and Glomerular Filtration Rate on Renal Outcome in Patients with Biopsy-Proven Benign Nephrosclerosis

Background

Reduced estimated glomerular filtration rate (eGFR) and proteinuria are risk factors for end-stage renal disease (ESRD), of which benign nephrosclerosis is a common cause. However, few biopsy-based studies have assessed these associations.

Methods

We performed retrospective cohort study of 182 Japanese patients who underwent renal biopsy from June 1985 through March 2014 and who were diagnosed with benign nephrosclerosis. Competing risk regression analyses were used to investigate the effect of eGFR and proteinuria levels at the time of renal biopsy on the risk for renal events (ESRD or a 50% decline in eGFR from baseline).

Results

During a median 5.8-year follow-up, 63 (34.6%) patients experienced renal events. The incidence of renal events increased with lower baseline eGFR and greater baseline proteinuria levels. After adjustment for baseline covariates, lower eGFR levels (subhazard ratios [SHRs], 1.30; 95% confidence interval [CI], 1.01–1.67, per 10 mL/min/1.73 m²) and higher proteinuria levels (SHR, 1.52; 95% CI, 1.23–1.87, per 1.0 g/day) at the time of renal biopsy were associated independently with higher risk for renal events. Lower levels of serum albumin (SHR, 2.07; 95% CI, 1.20–3.55 per 1.0 g/dL) were also associated with renal events. Patients with both eGFR <30 mL/min/1.73 m² and proteinuria ≥0.5 g/day had a 26.7-fold higher risk (95% CI, 3.97–179.4) of renal events than patients with both eGFR ≥60 mL/min/1.73 m² and proteinuria <0.5 g/day.

Conclusions

Reduced eGFR and increased proteinuria as well as lower serum albumin at the time of renal biopsy are independent risk factors for renal events among patients with biopsy-proven benign nephrosclerosis.     

PLA2R Antibody Levels and Clinical Outcome in Patients with Membranous Nephropathy and Non-Nephrotic Range Proteinuria under Treatment with Inhibitors of the Renin-Angiotensin System

Patients with primary membranous nephropathy (MN) who experience spontaneous remission of proteinuria generally have an excellent outcome without need of immunosuppressive therapy. It is, however, unclear whether non-nephrotic proteinuria at the time of diagnosis is also associated with good prognosis since a reasonable number of these patients develop nephrotic syndrome despite blockade of the renin-angiotensin system. No clinical or laboratory parameters are available, which allow the assessment of risk for development of nephrotic proteinuria. Phospholipase A₂ Receptor antibodies (PLA₂R-Ab) play a prominent role in the pathogenesis of primary MN and are associated with persistence of nephrotic proteinuria. In this study we analysed whether PLA₂R-Ab levels might predict development of nephrotic syndrome and the clinical outcome in 33 patients with biopsy-proven primary MN and non-nephrotic proteinuria under treatment with blockers of the renin-angiotensin system. PLA₂R-Ab levels, proteinuria and serum creatinine were measured every three months. Nephrotic-range proteinuria developed in 18 (55%) patients. At study start (1.2±1.5 months after renal biopsy and time of diagnosis), 16 (48%) patients were positive for PLA₂R-Ab. A multivariate analysis showed that PLA₂R-Ab levels were associated with an increased risk for development of nephrotic proteinuria (HR = 3.66; 95%CI: 1.39–9.64; p = 0.009). Immunosuppressive therapy was initiated more frequently in PLA₂R-Ab positive patients (13 of 16 patients, 81%) compared to PLA₂R-Ab negative patients (2 of 17 patients, 12%). PLA₂R-Ab levels are associated with higher risk for development of nephrotic-range proteinuria in this cohort of non-nephrotic patients at the time of diagnosis and should be closely monitored in the clinical management.     

Urinary Fibrinogen Derivative Excretion and Intraglomerular Fibrin Deposition in Glomerulonephritis

The relations between glomerular fibrin deposition, urinary excretion of fibrinogen derivatives (F.D.), and proteinuria were explored in 81 patients with glomerulonephritis. A positive correlation existed between proteinuria and F.D. excretion even when no fibrin could be detected in the glomerulus. In two patients with tubular proteinuria F.D. excretion was also raised, suggesting that tubular reabsorption or catabolism of F.D. or both normally occur.Disproportionately high titres of F.D. were observed when fibrin was deposited in an extracapillary site, but mesangial fibrin deposition was not accompanied by a higher excretion of F.D. than that observed in patients in whom intraglomerular fibrin was not detected. These observations suggest that the immunofluorescent findings on renal biopsies should be the major criteria on which a trial of anticoagulants in proliferative glomerulonephritis might be instituted and that measurement of urinary F.D. is likely to be of value in monitoring therapy in patients with extracapillary fibrin deposition.     

An ultrastructural study of proliferative nephritis induced experimentally by a monoclonal antibody against mesangial cells: replacement of mesangial cells by cells of the monocyte-macrophage system

An experimental nephritis accompanied by transient proteinuria can be produced by an intravenous injection of the monoclonal antibody, 1-22-3, raised against isolated rat glomeruli. The present study deals with the ultrastructural changes in the glomeruli in rats after the injection of this antibody. At 2 h after injection, all the mesangial cells had completely degenerated and neutrophils invaded most mesangial areas. Monocytes occupied the vacant mesangial areas at 24 h and gradually increased in number over the next 4 days. At 4 and 6 days, macrophage-like cells, possibly derived from monocytes, underwent frequent mitosis, resulting in a remarkable proliferation of these cells. The interpretation of these cells as macrophages was strongly supported by the fact that they contained previously injected latex particles in large numbers. From 2 to 4 weeks after injection, the macrophage-like cells gradually transformed into cells indistinguishable from normal mesangial cells. In the present experimental nephritis where all mesangial cells were initially destroyed, cells of the monocyte-macrophage system appear to play a leading role in the pathogenesis of the ensuing proliferative glomerulonephritis, and represent the source of the replacing mesangial cells.