Urinary transforming growth factor-β in patients with glomerular diseases

We measured the urinary levels of active transforming growth factor-β (TGF-β) by enzyme-linked immunosorbent assay in 12 healthy controls and 42 patients with various glomerular diseases, including mesangial proliferative (IgA nephritis, Henoch-Sch?nlein purpura nephritis, and IgA-negative mesangial proliferative glomerulonephritis) and non-proliferative (minimal change nephrotic syndrome and focal glomerulosclerosis) types. Urinary TGF-β, expressed as a ratio to urinary creatinine (ng/mg creatinine), was elevated in patients with IgA nephritis and focal glomerulosclerosis, and was significantly higher than in patients with other types of glomerular diseases and healthy controls. There was a significant correlation between urinary TGF-β levels and the grade of interstitial fibrosis. Among patients with proliferative-type disease, urinary TGF-β was significantly correlated with the grade of mesangial matrix increase and the magnitude of proteinuria. The relationship between urinary TGF-β levels and the immunostaining intensity of TGF-β in the glomeruli was not significant. These results indicated that urinary TGF-β reflects the grade of interstitial fibrosis in glomerular diseases and also the mesangial matrix increase in proliferative-type glomerulonephritis. Measuring TGF-β levels in the urine might be helpful in monitoring patients with some types of glomerular disease. Received November 20, 1995; received in revised form October 8, 1996; accepted October 18, 1996     

Parietal epithelial cells and podocytes in glomerular diseases

In recent years, it has become apparent that parietal epithelial cells (PECs) play an important role within the renal glomerulus, in particular in diseased conditions. In this review, we examine current knowledge about the role of PECs and their interactions with podocytes in development and under physiological conditions. A particular focus is on the crucial role of PECs and podocytes in two major glomerular disease entities. In rapidly progressive glomerulonephritis, PECs and podocytes proliferate and obstruct the tubular outlet, resulting in loss of the affected nephron. In focal and segmental glomerulosclerosis, PECs become activated and invade a segment of the glomerular tuft via an adhesion. From this entry site, activated PECs displace podocytes and deposit matrix. Thus, activated PECs are involved in inflammatory as well as degenerative glomerular diseases, which both can lead to irreversible loss of renal function.     

Relationship between urinary podocytes and kidney diseases

Podocyte loss is an important component of disease progression in glomerular diseases. To some extent, the loss of podocytes can predict the degree of damage and the advancement of renal disease. Detecting the loss of podocytes in the urine could be a valuable, noninvasive method for obtaining information about the activity of the disease or the disease type, allowing the early diagnosis of glomerular diseases. One of the most robust markers that has been successfully used for urinary podocyte diagnostics is podocalyxin (PDX). PDX is a sialoprotein that is expressed on podocytes and on a variety of nonrenal cells as well as on glomerular endothelial and parietal epithelial cells. Therefore, podocyte loss can be detected by the amount of PDX in the urine. The relationship between urinary podocytes and renal diseases is supported by the detection of podocytes in patients with immunoglobulin A (IgA) nephropathy, Henoch-Sch?nlein purpura nephritis, lupus nephritis, diabetic nephropathy, and focal segmental glomerulosclerosis. The use of technology for detecting podocytes in the urine would have broad implications for the evaluation of disease activity, the degree of dedifferentiation, and the possibility of regeneration.     

Causes of hyperhomocysteinemia in patients with chronic kidney diseases

Plasma homocysteine (Hcy) levels are increased significantly in patients with moderate renal failure and increase markedly in patients with end-stage renal disease. An increase in plasma Hcy level theoretically could be caused by an increased production rate (ie, transmethylation), a decreased rate of removal by transsulfuration or remethylation, or a decrease in the excretion of Hcy. Current evidence indicates that the major mechanism for hyperhomocysteinemia in renal failure is a decrease in Hcy removal from the body. However, it is debated whether this effect is the result of a decrease in the renal metabolic clearance or a result of extrarenal metabolic changes. The human kidney plays a major role in the removal of several aminothiols or Hcy-related compounds from the circulation (eg, cysteine-glycine, glutathione, AdoMet, and AdoHcy). However, the glomerular filtration of Hcy seems to be restricted because of protein binding. Besides glomerular filtration, the normal kidney can remove Hcy by plasma flow and peritubular uptake. Although in the low normal range in absolute terms, the flow through the transsulfuration pathway is reduced if related to Hcy levels in uremia; in addition, the remethylation pathway also is impaired. Besides the potential effect of the reduced renal mass on Hcy removal, available evidence suggests the occurrence of a generalized down-regulation of the methionine cycle and catabolism in uremia. AdoHcy, sulfate, and dimethylglycine currently are being investigated as retained solutes that can inhibit 1 or more pathways of Hcy metabolism. In addition, the high Hcy levels decrease in malnourished end-stage renal disease patients and change according to nutrient intake and several other nutritional parameters, indicating that circulating Hcy levels become an expression of nutritional status.     

Assessment of glomerular filtration rate in elderly patients with chronic kidney disease

Purpose

We sought to evaluate various glomerular filtration rate (GFR) estimating equations in elderly patients with chronic kidney disease (CKD).

Methods

A total of 332 Chinese elderly patients with CKD who had undergone technetium-99m diethylenetriaminepentaacetic acid (^99mTc-DTPA) renal dynamic imaging were enrolled. The MDRD equation, the re-expressed MDRD equation, the Chinese equation, the Ruijin equation, the previously Japanese equation, the new Japanese equation, the CKD-EPI equation, and the BIS1 equation were compared.

Results

The median of difference between estimated GFR and standard GFR ranged from ?9.78 to 1.79 ml/min/1.73 m². The interquartile range of difference ranged from 12.38 to 20.87 ml/min/1.73 m². Accuracy with a deviation <30 % ranged from 44.9 to 66.3 %. However, none of the equations had accuracy up to the 70 % level. Bland–Altman analysis demonstrated that the precision ranged from 50.5–87.6 ml/min/1.73 m². The slopes of regression line ranged from ?0.26 to 0.55 and the intercepts ranged from ?18.71 to 11.07. In both the overall performance and the performances in different stage of CKD, GFR estimated by the BIS1 equation performed better results.

Conclusion

None of the GFR estimating equations are suitable for the specific Chinese population tested. At present, the BIS1 equation may be the optimal one for elderly Chinese CKD patients.     

Urinary excretion of podocytes in patients with diabetic nephropathy.

BACKGROUND: Detection of podocytes in the urinary sediments of children with glomerulonephritis has been shown to indicate severe injury to the podocytes. The aim of the present study was to determine whether podocytes are present in the urine sediments of adult patients with diabetes with and without nephropathy and whether trandolapril is effective for podocyte injury. METHODS: Fifty diabetic patients (10 with normoalbuminuria, 15 with microalbuminuria, 15 with macroalbuminuria and 10 with chronic renal failure) and 10 healthy controls were studied. Urinary podocytes were examined by immunofluorescence using monoclonal antibodies against podocalyxin, which is present on the surface of podocytes. In addition, we studied plasma metalloproteinase (MMP)-9 concentrations in all patients. RESULTS: Urinary podocytes were absent in healthy controls, diabetic patients with normoalbuminuria and diabetic patients with chronic renal failure. Podocytes were detected in the urine of eight diabetic patients with microalbuminuria (53%) and of 12 patients with macroalbuminuria (80%). The number of podocytes in the urine of patients with macroalbuminuria was significantly greater than in patients with microalbuminuria (P:<0.01). However, there was no relationship between urinary albumin excretion and urinary podocytes. In addition, plasma MMP-9 concentrations were significantly correlated with the number of urinary podocytes (P:<0.01). Twelve diabetic patients with macroalbuminuria and eight patients with microalbuminuria who had urinary podocytes were treated with the angiotensin-converting enzyme inhibitor trandolapril. Urinary albumin excretion, the number of podocytes and plasma MMP-9 concentrations were reduced by the trandolapril treatment. CONCLUSIONS: Podocytes in the urine may be a useful marker of disease activity in diabetic nephropathy. Trandolapril may be effective for podocyte injury.     

Urinary sediment features in proliferative and non-proliferative glomerular diseases

BACKGROUND: The studies on urine sediment particles in patients with glomerular diseases (GD) are few and have focused only on single urine particles. In this study, we investigated the prevalence and number of 12 urine sediment particles in two groups of patients, one with proliferative GD, and the other with non-proliferative GD. METHODS: The urine sediment of 100 consecutive patients, with a renal biopsy-proven proliferative or non-proliferative GD and marked cylindruria, were examined a few hours before renal biopsy according to a standardized method. The urine particles investigated were erythrocytes, leukocytes, renal tubular cells, lipids and hyaline, hyaline-granular, granular, waxy, erythrocytic, leukocytic, epithelial and fatty casts. RESULTS: Patients with proliferative GD (n=52) had both a significantly higher prevalence of microscopic hematuria, leukocyturia, tubular epithelial cells, erythrocytic casts, epithelial casts, and significantly higher amounts of erythrocytes,leukocytes, tubular epithelial cells/20 high power field (HPF), erythrocytic and epithelial casts. On the other hand, patients with non-proliferative GD (n=48) had significantly higher numbers of fatty casts. In proliferative GD, leukocyturia was associated with intracapillary and extracapillary proliferation, crescents and fibrinoid necrosis at renal biopsy. At discriminant analysis, the two types of GD could be identified with 80.8% sensitivity and 79.2% specificity. By multiple logistic regression analysis, patients with erythrocytes, leukocytes and erythrocytic casts in the urine had an odds ratio (OR) of 9.91 (95% confidence interval (95% CI): 1.01-97.51), 7.85 (95% CI: 2.77-22.20), and 4.33 (95% CI: 1.41-13.31), respectively, of having proliferative GD. CONCLUSIONS: Our examination of the urine sediment shows that proliferative GD and non-proliferative GD differ in many respects.     

Correlation of kidney size with kidney function and anthropometric parameters in healthy subjects and patients with chronic kidney diseases

Abstract

Background/Aim: Echosonography is a simple, noninvasive method of kidney visualization. The objective of this study was to compare the kidney echosonograpic characteristics with the kidney function and anthropometric characteristics in healthy subjects and patients with the chronic kidney disease (CKD). Methods: The study involved 49 patients (21 men; 46.02?±?14.27 years) with CKD and the control group of 46 healthy persons (20 males; 45.45?±?18.48 years). Physical examination, kidney echosonography and laboratory analyses including creatinine clearance (Ccr; 24?h and calculated by Cockroft--Gault (C--G) formula) were done in all persons. Results: There was no significant difference in age and sex between two groups but serum creatinine concentration was significantly higher (218.8 vs. 84.5?μmol/L) and Ccr significantly lower (66.44 vs. 94.20?mL/min, C--G) in patient group. The left kidney was larger in both groups, but the only significant difference was in kidney depth (p?<?0.01). There was significant correlation between all measured kidney dimensions, volume, parenchymal thickness and serum creatinine concentration and Ccr (C--G) in patient group. In the controls, there was no significant correlation between the kidney size and function, but there was a significant correlation between the kidney width, depth, volume and patients’ age and anthropometric parameters. On the contrary, all analyzed parameters of kidney size, except volume, did not correlate significantly with the anthropometric parameters of patients. Conclusion: Kidney size of patients with CKD correlated significantly with kidney function, while correlation with anthropometric parameters, which is otherwise present in healthy subjects, was lost in patients with CKD.     

Recent insights into kidney diseases associated with glomerular cysts

Glomerular cysts can exist in the context of several different kidney diseases. Advances in the last few years have begun to unravel the genetic bases and pathogenesis of some of these entities, many of which have an origin in abnormal development. In this review, we highlight recent insights into three types of disease associated with glomerular cysts: (1) mutations of the hepatocyte nuclear factor 1β (HNF-1β) in the recently described renal cysts and diabetes syndrome, (2) mutations of OFD1 in the oral facial digital syndrome type 1 and (3) the role of fetal urinary tract obstruction. Received: 10 August 2001 / Revised: 7 December 2001 / Accepted: 10 December 2001     

Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.     

慢性肾脏病患者血栓调节蛋白与动脉粥样硬化的相关性

目的 探讨慢性肾脏病(CKD)患者血栓调节蛋白（Tm）水平与动脉粥样硬化（AS）的相关性。 方法 以北京朝阳医院肾内科住院的96例CKD患者为对象,其中血液透析32例,非透析64例;30例健康志愿者为对照。参试者均于清晨空腹采静脉血,分别测定Scr、胆固醇、三酰甘油、高密度脂蛋白、低密度脂蛋白、C反应蛋白、血红蛋白及血栓调节蛋白。应用彩色多普勒超声检测颈动脉内膜中层厚度（IMT）。对血栓调节蛋白与IMT及相关参数进行相关分析。 结果 CKD患者血栓调节蛋白为（12.15±3.04） mg/L,显著高于健康对照组的（3.12±0.23） mg/L（P < 0.01）。血液透析组血栓调节蛋白为（16.89±3.35） mg/L,显著高于非透析组的（9.78±2.49） mg/L（P < 0.01）。血液透析组IMT值为（1.13±0.31） mm,斑块检出率为48.5%,均显著高于非透析治疗组的（0.95±0.33） mm和28.7%（均P < 0.05）。96例CRF患者的Tm水平与IMT呈正相关（r = 0.335,P < 0．01）。动脉病变程度越重者,血浆Tm水平越高。多元逐步回归分析结果显示,Tm（OR=1.13,95%CI 1.010~1.121）、SBP（OR=1.09,95%CI 1.009~1.114）、CRP（OR=1.22,95%CI 1.216~2.007）分别与CKD患者IMT独立相关。 结论 CKD患者Tm水平与IMT独立相关。血管内皮细胞损伤与CKD患者动脉粥样硬化并发症密切相关。Tm有可能成为血管内皮细胞损伤或功能紊乱的标志物。     

Cytokines in chronic kidney disease: potential link of MCP-1 and dyslipidemia in glomerular diseases

Background

Many studies have indicated a role for cytokines in chronic kidney disease (CKD). The aim of this study was to evaluate plasma and urinary levels of monocyte chemoattractant protein-1 (MCP-1/CCL2), transforming growth factor-beta1 (TGF-β1), and interleukin-8 (IL-8/CXCL8) in pediatric patients with CKD stages 2–4.

Methods

Cytokines were measured in 37 healthy controls and in 42 CKD patients by enzyme-linked immunoassay. Patients were divided into groups according to CKD etiology: glomerular disease (group 1, n?=?11) and congenital anomalies of the kidney and urinary tract (group 2, n?=?31). Urinary cytokine measurements were standardized for creatinine.

Results

Plasma and urinary levels of MCP-1/CCL2 were significantly higher in both CKD groups compared to the control group. Between the two CKD groups, only urinary MCP-1/CCL2 levels were significantly different, with MCP-1/CCL2 levels higher in group 1 patients. Plasma and urinary levels of IL-8/CXCL8 and TGF-β1 were undetectable in the control group but comparable between the two CKD groups. In group 1 patients, urinary MCP-1/CCL2 levels were negatively correlated to serum albumin levels and positively correlated to the levels of total cholesterol and triglycerides. In group 2 patients, urinary levels of IL-8/CXCL8 were negatively correlated with the estimated glomerular filtration rate and positively correlated with body mass index.

Conclusions

Differences in cytokine profiles may be related to CKD etiology and other disease-associated alterations.     

Glomerular podocytes and adhesive interaction with glomerular basement membrane

Normal podocyte function requires attachment to the underlying glomerular basement membrane. Alteration or disruption of podocyte attachment occurs in many forms of glomerular injury, leading to the development of proteinuria and eventually progressive glomerulosclerosis. The inability of podocytes to proliferate and thereby recover denuded glomerular basement membrane areas may be central to the pathogenesis of certain forms of glomerular diseases.     

Impact of percutaneous nephrolithotomy on estimated glomerular filtration rate in patients with chronic kidney disease

BACKGROUND AND PURPOSE: We investigated the impact of percutaneous renal procedures on estimated glomerular filtration rate (GFR) of patients with chronic kidney disease (CKD). PATIENTS AND METHODS: The GFRs of adult patients were calculated using the Modification of Diet in Renal Disease formula, and the patients were staged according to the Kidney Disease Outcome Quality Initiative CKD classification system. The study included 185 patients with preoperative GFR values less than 60 mL/min/1.73 m(2). The impact of percutaneous nephrolithotomy (PCNL) on GFR was analyzed by comparing the preoperative GFR with the GFR before discharge and at postoperative month 3. RESULTS: Patients with CKD had a significant increase in the GFR after the procedure. In postoperative month 3, the mean GFR was more than 60 mL/min/1.73 m(2) in 25% of the patients with CKD and less than 60 mL/min/1.73 m(2) in 75%. While all patients with stage 5 CKD improved to better stages, some other patients' conditions declined to stage 5 from better stages at the end of postoperative month 3. No patient needed dialysis. The presence of urinary tract infections tended to affect GFR negatively. CONCLUSION: Estimated GFR, as a better indicator of renal function, is significantly affected by the PCNL procedure. While significant improvement was observed in late-stage patients with CKD, unexpected deterioration could occur in patients at earlier stages.     

Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases

Background Electron-dense deposits are often found around glomerular capillary lumens in patients with glomerulonephritis, forming a portion of the blood-urine barrier (BUB). Methods Four hundred and four patients with primary glomerular diseases or donors for living-related kidney transplantation who underwent both percutaneous renal biopsy and renal clearance tests were included in the study. Sodium thiosulfate and paraamino hippurate double-clearance studies were performed with catheterized urinary collection. The filtration fraction (FF) was determined as follows: FF = sodium thiosulfate clearance/paraamino hippurate clearance (Cpah). Histomorphometric analyses were performed in 53 patients with overt para-capillary electron-dense deposits (PCEDD) by electron microscopic observations. Results Patients with membranous nephropathy and membranoproliferative glomerulonephritis showed significantly lower levels of FF than the donors for living-rebated kidney transplantation (normal controls). FF levels were significantly lower in patients with PCEDD than in those without (P < 0.001), while the levels of mean blood pressure and Cpah were comparable in the two groups. The PCEDD/BUB ratio demonstrated a significant negative correlation with FF (P < 0.0001; r² = 0.331). Patients with a ratio of 0.5 or more showed significantly lower FF levels than those with a ratio of 0.25 or less. Conclusions PCEDD significantly affected FF levels in patients with primary glomerular diseases. FF may not be an accurate indicator of intraglomerular blood pressure in patients with overt PCEDD.