Clinical importance of the radioimmunologic determination of beta 2-microglobulin in patients with kidney pathology

High diagnostic significance of beta 2-microglobulin determination by radioimmunoassay in the blood and urine of patients with the main types of renal pathology (chronic glomerulonephritis, chronic pyelonephritis, hemorrhagic fever with the renal syndrome, and diabetic nephropathy) was shown. A study of beta 2-microglobulin level permitted accurate determination of the localization of pathology in the nephron and assessment of a degree of its expression as well as the detection of initial renal functional disorders, assessment of therapeutic efficacy and dynamic observation of renal function in patients with renal pathology.     

Immune complex hyperuricemic nephritis: aspects of its morphology and pathogenesis

The authors described the results of an immunohistochemical, electron microscopic and morphometric study of the kidney bioptates of 45 patients with latent glomerulonephritis with hyperuricemia, 8 patients with primary gout and 12 patients with latent glomerulonephritis without hyperuricemia. Two possible variants of the involvement of the renal glomerula were revealed against a background of purine metabolism: typical immunocomplex glomerulonephritis and the so called "reactive" mesangial changes. The expression of interstitial changes (by the results of histometric investigation) was maximum in gout, slightly less in latent nephritis with hyperuricemia and minimum in nephritis without hyperuricemia. The authors emphasized the possibility of immunocomplex nephritis as one of the variants of renal lesion in gout and hyperuricemia and the necessity of specifying therapeutic modalities to be used in this condition including general nephrological approaches to the treatment of latent nephropathies.     

The significance of microproteinuria for the diagnosis of kidney involvement in hypertensive disease and secondary forms of arterial hypertension]

N-acetyl-beta-glucosaminidase (NAG) activity, the concentrations of microalbumin (MA) and B2-microglobulin (B2-MG) were measured in urine of 50 healthy subjects and 200 patients suffering from arterial hypertension (AH) with preserved renal function, including patients with essential hypertension (EH), stages I and II, chronic pyelonephritis (CPN), chronic glomerulonephritis (CGN) and vasorenal hypertension (VRH). The healthy subjects, the patients with stage II EH, and those with secondary forms of AH demonstrated significant differences in NAG activity in urine. A positive correlation (r = +0.53; p < 0.03) was discovered between systolic AP and NAG activity in urine of EH patients. The concentration of MA in urine of CGN and VRH patients was significantly higher than that in the healthy subjects, EH and CPN patients. The patients with CPN and VRH showed significantly higher levels of B2-MG in urine.     

Hyperuricemia as a risk factor of nephropathy in gout

Among 196 patients with primary gout examined in hospital or earlier stable or transient hyperuricemia was noted in 160 (81.6%). These patients were entered into the study group. The control group included 36 persons in whom the level of blood uric acid did not exceed normal values. The familial pattern of disease was established in the patients of the study group. Urolithic, proteinuric and hypertensive types of nephropathy as well as chronic renal insufficiency were more frequently observed in hyperuricemia patients. Alongside with severe tubular, interstitial and vascular changes, glomeruli in the form of mesangioproliferative or mesangiocapillary glomerulonephritis were regularly involved in the pathological process. In the rest of the patients vascular lesions were less marked and less frequent, renal glomerular changes reminded the picture of mesangioproliferative glomerulonephritis only; urolithiasis in them took a more favorable course. Thus, a high level of blood uric acid is one of the risk factors of renal affection in gout determining in many ways prognosis of disease.     

Role of IL-8 and defensins in pathogenesis of chronic glomerulonephritis and pyelonephritis]

AIM: The study of interleukine-8 (IL-8) and defensines contribution to pathogenesis of chronic glomerulonephritis (CGN) and pyelonephritis (PN). MATERIALS AND METHODS: 122 patients were assigned to three groups: 42 CGN patients with isolated urinary syndrome (group 1); 60 patients with chronic pyelonephritis (CP) with normal nitrogen-excretory function (group 2); 20 patients with CGN and chronic renal failure (CRF) (group 3). 24 healthy volunteers served control. IL-8 and defensines were measured in urine and plasm of all the patients and controls using enzyme immunoassay. RESULTS: IL-8 in urine and plasm of controls was not found, in plasm of patients was found in 45%, the differences between the groups being insignificant. The highest IL-8 urine concentration was found in group 2. It was significantly higher than in group 1 and 3 (p < 0.001). Mean IL-8 urine concentration in patients with secondary pyelonephritis was significantly higher than in those with primary pyelonephritis (p < 0.05). In primary pyelonephritis, urinary IL-8 was higher than in patients of groups 1 and 3 (p < 0.001). Mean urinary IL-8 was significantly higher in patients of group 3 than 1 (p < 0.005). IL-8 urinary concentrations of group 3 patients tended to an increase with growing severity of renal failure. Plasm defensines were present in 46.5% of patients without marked differences between the groups. Urine defensines were the highest in group 2 being significantly higher than in group 1, 3 and controls (p < 0.001). Urine defensines in group 1 were slightly higher than in controls and significantly reduced vs group 3 (p < 0.005). Urine defensines concentrations rose with CGN stage. A strong positive correlation was established between IL-8 and defensines in urine (r = 0.62), leukocyturia and IL-8 in urine (r = 0.52). A weak positive correlation (r = 0.38) existed between proteinuria and urine IL-8 only in group 3 patients. A week later concentrations of IL-8 and defensines were low in group 2. In group 1 they rose, fell or remained unchanged. CONCLUSION: IL-8 and defensines may be of the same pathogenetic importance both in infectious and non-infectious inflammation in the kidneys. Cytotoxic action of defensines can be related to location of the inflammation in the kidney. IL-8 urine tests can be used in monitoring of inflammation activity and diagnosis of latent glomerulonephritis and pyelonephritis.     

A comparative study of serum alpha 1-microglobulin and beta 2-microglobulin levels in cancerous and other diseases

The levels of serum alpha 1-microglobulin in 60 normal persons and in 191 patients suffering from a variety of benign and malignant disorders were determined by an enzyme immunoassay, and these values were compared with the levels of beta 2-microglobulin. A discrepancy between the serum levels of these proteins was found in hepatobiliary disorders; that is, an increased serum level of beta 2-microglobulin was observed in 73.9%, while in only 4.3% was there an elevation of alpha 1-microglobulin. In particular, alpha 1-microglobulin levels in patients with liver cirrhosis were well below the normal range, while beta 2-microglobulin levels were elevated. Elevated levels of both proteins were noted in patients with some impairments of renal function, particularly in chronic renal failure, and in immunological diseases. In 81 patients with neoplastic diseases, a high alpha 1-microglobulin value was found in only 15 patients (16.4%), while a high beta 2-microglobulin value in 62 patients (76.5%). The serum levels of both alpha 1-microglobulin and beta 2-microglobulin were especially high in plasma cell dyscrasia with Bence Jones protein, but other neoplastic diseases were mostly associated with beta 2-microglobulin elevation alone.     

Beta 2-microglobulin concentration in plasma and production in liver cirrhosis

The beta 2-microglobulin plasma level is often high in patients suffering from cirrhosis. Many authors believe this to be due to an increased production, provided that the creatinine level is in the normal range. In the present study, alterations in the plasma level and production of beta 2-microglobulin were investigated in patients with liver cirrhosis without overt renal failure. 62 patients, 48 men and 14 women, suffering from liver cirrhosis were examined. The glomerular filtration rate (GFR) and plasma beta 2-microglobulin were measured in all patients and in 16 controls. As beta 2-microglobulin is freely filtered by glomeruli and its extrarenal catabolism is negligible, the beta 2-microglobulin filtration rate was calculated as the product of the beta 2-microglobulin plasma level times the GFR. In steady state conditions, the beta 2-microglobulin filtration rate may be used as an indirect index of beta 2-microglobulin production. The beta 2-microglobulin plasma level was high in 26 patients; however, only 12 of them showed a definite rise in beta 2-microglobulin production, as shown by an increased beta 2-microglobulin filtration rate. The 14 patients with high beta 2-microglobulin plasma levels without high beta 2-microglobulin filtration rates obviously showed a decreased GFR; however, creatinine was not increased because of its small sensitivity as an index of renal function. A linear correlation was found between IgG and the beta 2-microglobulin filtration rate (r = 052; p less than 0.02), not between IgG and the beta 2-microglobulin plasma level. The other indices of liver damage were not related to the beta 2-microglobulin filtration rate of plasma level.     

Serum beta2-microglobulin in liver disease.

The concentration of beta 2-microglobulin in serum was determined in seventy-one patients with various liver disorders. Elevated values were found in most patients with chronic active or chronic persistent hepatitis and in over 80% of patients with alcohol-induced liver cirrhosis. In contrast, patients with alcohol-induced fatty liver, the serum beta 2-microglobulin concentrations were mostly within the normal range. Significant correlation (P less than 0.001) was noted between the elimination rate of galactose from blood and the serum beta 2-microglobulin concentration in patients with alcoholic liver damage but not in patients with chronic hepatitis. The reasons for the increased S-beta 2-microglobulin concentrations in liver diseases are unknown. Several explanations including a release of beta 2-microglobulin from necrotic liver cells or an increased synthesis of beta 2-microglobulin consequent to inflammation in the liver are possible. Alternatively, raised beta 2-microglobulin levels may reflect the hepatic synthesis during reparative growth.     

Differentiation of glomerular, tubular, and normal proteinuria: determinations of urinary excretion of β2-microglobulin, albumin, and total protein

A low molecular weight beta(2)-globulin (beta(2)-microglobulin), albumin, and total protein were measured in concentrated 24-hr urine specimens from 20 healthy subjects and 30 patients with clinical proteinuria of glomerular or tubular type. Classification of proteinuria was made on the basis of clinical diagnosis and size distribution of urinary proteins after gel chromatography. The molecular radii (Stokes' radii) of beta(2)-microglobulin and albumin, estimated by gel chromatography, were 15 A and 35 A.The average 24-hr urinary excretion in healthy subjects was 0.12 mg for beta(2)-microglobulin, 10 mg for albumin, and 80 mg for total protein. The patients with renal glomerular disorders had normal or only somewhat increased excretion of beta(2)-microglobulin, despite considerably increased excretion of albumin and total protein. Most of the patients with tubular dysfunction excreted large amounts of beta(2)-microglobulin, although they excreted normal or only slightly increased amounts of albumin and only moderately increased quantities of total protein. Consequently, the ratio or urinary albumin/urinary beta(2)-microglobulin was high in glomerular proteinuria (1100: 14,200), intermediate in normal proteinuria (33: 163), and low in tubular proteinuria (1.0: 13.3). Determinations of urinary clearances of beta(2)-microglobulin and albumin in four healthy subjects and 11 patients indicated that increased excretions of the two proteins were associated with increased clearances. The results suggest that quantitative determinations of urinary beta(2)-microglobulin and urinary albumin may be useful for detecting disorders of the renal handling of plasma proteins. The findings also seem to suggest a selective tubular reabsorption of the two proteins.Estimates on sera revealed a close correlation between serum levels of beta(2)-microglobulin and creatinine and also a greatly raised serum concentration of beta(2)-microglobulin after bilateral nephrectomy.     

尿液吞噬细胞检测在泌尿系统疾病诊断中的应用价值

目的　分析817 例尿液标本吞噬细胞的检测结果,评价吞噬细胞在泌尿系统疾病诊断中的应用价值。方法　选 取西京医院检验科尿液红细胞形态门诊2019 年1 ～ 12 月就诊患者817 例,其中原发性肾小球肾炎患者623 例,继发性 肾病患者61 例,急性肾盂肾炎患者12 例,急性膀胱炎患者20 例,慢性上尿路感染患者41 例,正常尿液成分组19 例, 观察尿液有形成分中吞噬细胞形态并统计其在不同疾病组的检出率,进行统计分析。结果　正常尿液成分组吞噬细胞检 出率15.79%。与正常尿液成分组相比较,急性肾盂肾炎组检出率100%,急性膀胱炎组检出率100%,原发性肾小球肾 炎组吞噬细胞检出率86.35%,继发性肾病组吞噬细胞检出率67.21%,慢性上尿路感染组吞噬细胞检出率60.97%,差异 均有统计学意义（χ2=10.651~64.036,均P<0.01）。其中在急性泌尿系统感染检出率最高,其次为原发性肾小球肾炎。 在不同疾病中吞噬细胞形态有所差异,在泌尿系感染时多见大吞噬细胞,在原发性肾小球肾炎时多见小吞噬细胞。结论　 吞噬细胞不仅在尿路感染中有很高的检出率,在肾小球相关疾病中也有较高的检出率,且形态有所不同。     

Urinary excretion of beta 2-microglobulin in myeloma patients

The levels of beta 2-microglobulin in urine and serum were determined in 39 patients with myelomatosis. In 25 patients the serum beta 2-microglobulin was elevated, and in seven of the patients with increased serum beta-microglobulin the urinary excretion of the protein was also increased. It was concluded that the increased urine beta-microglobulin indicates a renal tubular disorder.     

Renal handling of beta2-microglobulin in experimental renal disease.

Renal extraction and urinary excretion of 125I-labelled beta2-microglobulin was studied in rats. The effect of ischaemic renal injury, experimental pyelonephritis, and unilateral nephrectomy was investigated. The tubular secretion of o-iodohippurate (OIH) was measured for comparison. The urinary excretion was calculated as the ratio between the clearance of protein and the glomerular filtration rate. The glomerular filtration rate was estimated as clearance of polyethylene glycol (PEG 1000). The renal arteriovenous concentration difference was lower for beta2-microglobulin than for PEG 1000 IN ALL THE EXperimental groups. In unilateral renal disease the beta2-microglobulin excretion of the intact kidneys was similar to that of the diseased kidneys. A significant differences was noted only after ischaemic renal injury. The same was found for OIH. After removal of the intact kidneys the excretion of beta2-microglobulin increased about 10-fold in pyelonephritic animals and 2- to 30-fold in animals with ischaemic renal injury. One hour after unilateral nephrectomy in normal animals the ratio increased about 50 per cent. The tubular secretion of OIH did not change noticeably. It is concluded that the glomerular filtration is a main step in the intrarenal catabolism of beta2-microglobin and that its urinary excretion is considerably influenced by a reduction in the functioning kidney mass.     

Familial gout

The authors observed 10 patients from 4 families with hereditarily determined gout and detected some specific features in its course. The familial disease was sex-unrelated, its first signs manifested themselves early acquiring a subsequent severe course; purine metabolic derangement was of a metabolic type, a urolithic form of nephropathy was seldom observed. A morphological picture was characterized by a glomerular lesion looking like focal segmental mesangiocapillary or mesangioproliferative glomerulonephritis with noticeable changes in the tubules, stroma and vessels causing early renal insufficiency. Pathogenetic therapy with uricodepressants made it possible to improve the course of nephropathy. The authors described a pedigree of 3 generations of a family in which gout developed in its 10 out of 17 members, in 6 with chronic renal insufficiency.     

Update on gout and hyperuricemia

There have been recent advances in the understanding of underlying mechanisms and treatment of gout and chronic hyperuricemia, making this an important time to review the current state of the disease. The goal of this article is to provide a practical review of the current standard of care as well as discuss some new developments in the management. There is an increasing prevalence of gout and hyperuricemia worldwide. Gout confers a significant individual and societal burden and is often under‐treated. Appropriate diagnosis and treatment of acute gout should be followed by aggressive and goal‐oriented treatment of hyperuricemia and other risk factors. Allopurinol remains as a first‐line treatment for chronic hyperuricemia, but uricosuric agents may also be considered in some patients. Febuxostat, a non‐purine xanthine‐oxidase inhibitor, is a new agent approved for the treatment of hyperuricemia in patients with gout, which may be used when allopurinol is contraindicated. Gout and hyperuricemia appear to be independent risk factors for incident hypertension, renal disease and cardiovascular disease. Physicians should consider cardiovascular risk factors in patients with gout and treat them appropriately and aggressively.     

Renal pathology and proteinuria determine progression in untreated mild/moderate chronic renal failure

The progression of renal failure was analyzed in 108 patients with mild to moderate renal impairment, none of whom had received any form of dietary protein, phosphate restriction or immunosuppressive treatment. The reciprocal of plasma creatinine was plotted against time using a minimum of six plasma creatinine values taken over at least six months (mean 13 values over 41 months). Plots indicated there was linear deterioration in 70 patients, non-linear deterioration in 15 and stable renal function in 24. Progressive renal failure was common in patients with glomerulonephritis, diabetic nephropathy, chronic pyelonephritis and polycystic kidney disease. Most patients with hypertensive nephrosclerosis, analgesic nephropathy and renal impairment following acute renal failure were stable. Among those with progressive impairment the mean rates of deterioration were significantly faster for patients with glomerulonephritis and diabetic nephropathy compared to those with chronic pyelonephritis, polycystic kidney disease and undiagnosed renal disease (p less than 0.01). Hence the underlying renal pathological changes appear to be important in determining progression of renal failure and also the subsequent rate of deterioration. For those with linear progression of renal failure there was a significant correlation between 24-h urinary protein excretion and the rate of deterioration. This relationship held for glomerulonephritis and chronic pyelonephritis as separate diagnostic groups only. Proteinuria, therefore, may be a useful prognostic index for the rate of progression of established renal failure. Calcium phosphate product correlated poorly with the rate of deterioration. We were unable to demonstrate a relationship between spontaneous protein intake and deterioration of renal function. However, patients prescribed high protein diets were not included in dietary analysis and we cannot, therefore, exclude the possibility that a high dietary protein intake may accelerate renal failure. Similarly we were unable to show a significant relationship between blood pressure and progression of renal failure although there were weak correlations between mean arterial pressure and rate of deterioration for chronic pyelonephritis and glomerulonephritis.     

Properdin and C3 Proactivator: Alternate Pathway Components in Human Glomerulonephritis

Serological and immunopathological studies of human glomerulonephritis have suggested that alternate pathways of activation of the third component of complement may be important in some forms of glomerulonephritis. We have investigated the role of two alternate pathway proteins, properdin and C3 proactivator, in 22 patients with chronic membranoproliferative glomerulonephritis, 21 patients with systemic lupus erythematosus, 20 patients with acute poststreptococcal glomerulonephritis, and 19 patients with other forms of renal disease. C3 (measured at beta(1)A), properdin, and C3 proactivator were assayed by single radial immunodiffusion.In sera with low beta(1)A (< 2 SD), mean properdin was most significantly decreased in patients with acute poststreptococcal glomerulonephritis but was also significantly decreased in chronic membranoproliferative glomerulonephritis and in untreated systemic lupus erythematosus. Properdin levels in other renal disease, acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis with normal beta(1)A levels were not significantly different from normal. A positive correlation between beta(1)A and properdin levels in individual sera was present in all diseases except systemic lupus erythematosus.Serum C3 proactivator was markedly decreased in active systemic lupus erythematosus and there was a positive correlation between beta(1)A and C3 proactivator levels in systemic lupus erythematosus and other renal diseases but not acute poststreptococcal glomerulonephritis.Properdin in fresh sera from four patients with systemic lupus erythematosus and five with chronic membranoproliferative glomerulonephritis showed increased migration toward the cathode on immunoelectrophoresis, suggesting in vivo change of the properdin molecule.The observation of reduced serum levels of properdin and C3 proactivator and altered electrophoretic migration of properdin in some patients with glomerulonephritis provide new evidence for participation of these alternate pathway proteins in glomerulonephritis.     

Gout nephropathy--ghost or reality?

Until the past decades, end stage renal disease was considered a major cause of death among patients with gout. Modern long-term follow up studies of renal function however have indicated that hyperuricemia and gout rarely result in kidney damage unless other renal diseases supervene. Subsequently, the use of the EDTA lead mobilization test confirmed that gout in the presence of chronic renal failure is a useful marker of chronic lead intoxication. Chelation treatment with EDTA can slow the progression of renal insufficiency, without apparent damage associated with the use of the chelating agent. Since chronic lead intoxication may remain clinically concealed for years, a high index of suspicion is warranted. Occult lead intoxication should be sought actively in gouty patients with chronic renal insufficiency of unknown etiology.     

Turnover in humans of β2-microglobulin: the constant chain of HLA-antigens

The turnover of beta 2-microglobulin, the common subunit of the HLA antigens, has been examined in normal subjects and in some patients with kidney disorders, multiple myeloma and rheumatoid arthritis. All patients displayed elevated serum levels of beta 2-microglobulin. The plasma disappearance curve of 125I-beta 2-microglobulin demonstrated that the protein has a rapid turnover (t 1/2 = 2.1 h; range 1.1-2.8 h) in normal persons and in patients with a normal glomerular filtration rate. In patients with kidney disorders the impaired renal filtration prolonged the turnover time and led to elevated serum levels of beta 2-microglobulin. Simultaneous measurements of 125I-beta 2-microglobulin in serum and urine allowed estimations of the beta 2-microglobulin net reabsorption in the renal tubuli. Two patients with renal disease reabsorbed 84% and 89%, respectively, of the beta 2-microglobulin filtered in the glomeruli. In normal persons the net reabsorption is close to 100%. In patients with normal kidney function increased serum levels of beta 2-microglobulin seem to be due to an increased synthetic rate of the protein as the elimination rate is normal. HLA antigen heavy chains in serum are present in smaller amounts than beta 2-microglobulin. The present data, therefore, suggest an imbalanced synthesis of the two chains.     

尿液分析中电导率的临床意义

目的探讨尿液分析中电导率的临床意义。方法(1)留取健康成人、孕妇、亚临床健康新生儿的尿液进行尿电导率;(2)随机留取40例各类病人尿液进行尿电导率、尿比重、尿素、肌酐、钾、钠、氯、钙检测;(3)留取急性肾小球肾炎、慢性肾小球肾炎、肾病综合症、肾结石、输尿管结石、糖尿病、高血压等病人的尿液进行尿电导率检测。结果(1)健康成人中男女无显著差异,晚孕孕妇、新儿生的电导率下降;(2)尿电导率与无机盐(钾、钠、氯、钙浓度之和)相关性最好(r=0.974),与肌酐、尿素、尿比重相关较差;(3)急性肾小球肾炎、慢性肾小球肾炎、肾病综合症、肾结石、输尿管结石、糖尿病、高血压等病人的尿电导率均偏低。结论尿电导率可以反应肾脏的浓缩功能。     

β2微球蛋白联合尿系列蛋白检测在无症状高尿酸血症肾损伤诊断中的应用及其临床意义

目的探讨血β2微球蛋白联合尿系列蛋白检测在无症状高尿酸血症肾损伤诊断中的价值。方法选取2016年3月至2018年1月于该院接受治疗的无症状高尿酸血症患者共98例,按照随机数字表法分为观察组、对照组,每组49例。对照组采用尿系列蛋白[微量清蛋白(MA)、免疫球蛋白(Ig)、转铁蛋白(TRU)和α1-微球蛋白(α1-MG)]诊断肾损伤,观察组在对照组的基础上联合血β2微球蛋白诊断肾损伤。选择同期入院检查的健康体检者49例为健康组,并接受血β2微球蛋白联合尿系列蛋白检测,比较3组研究对象以上指标的水平,以及对照组与观察组采用不同指标诊断肾损伤的阳性预测值、阴性预测值、特异度、灵敏度、约登指数。结果与健康组比较,观察组、对照组血β2微球蛋白、MA、Ig、TRU、α1-MG水平明显升高,差异有统计学意义(P<0.05);观察组、对照组阴性预测值、阳性预测值比较差异无统计学意义(P>0.05);而观察组特异度、灵敏度、约登指数明显高于对照组,差异有统计学意义(P<0.05)结论联合检测β2微球蛋白及尿系列蛋白对于无症状高尿酸血症肾损伤患者的诊断具有较高的价值,可有效提高检测的灵敏度与阳性预测值,对疾病的早期发现具有重要的临床意义。