Evaluation of criteria for the diagnosis of Balkan endemic nephropathy

BACKGROUND: The diagnosis of Balkan endemic nephropathy (BEN) is often made using Danilovic's criteria. The aim of this study was to determine the prevalence, sensitivity, specificity, and predictive value of Danilovic's criteria and several additional indices. METHODS: The study included 19 BEN patients, 23 BEN-suspected patients, 34 patients with other kidney diseases, and 23 healthy controls. The sensitivity and specificity of Danilovic's criteria was calculated, and these criteria, in addition to age, sex, blood pressure, creatinine clearance, glucosuria, urine osmolality, alkaline phosphatase, alpha 1-microglobulin, fractional sodium excretion, tubular phosphate reabsorption, kidney length, and volume, were combined in a logistic regression. RESULTS: All examined persons were from a BEN-affected village (criterion 1), and all BEN, BEN-suspected patients, and 12/23 healthy controls were from BEN families (criterion 2). None of the remaining Danilovic's criteria was found in the healthy controls. The prevalence of proteinuria, low specific gravity, and anemia (criteria 3-5) differed insignificantly among the patient groups. Azotemia and shrunken kidney (criteria 6 and 7) were significantly more frequent in BEN than in other patients. Only proteinuria showed high sensitivity and specificity in differentiating BEN and BEN-suspected patients from healthy persons, but no criteria differentiated BEN or BEN-suspected from other kidney diseases. Proteinuria is a significant predictor of both BEN and BEN-suspected vs. healthy persons, and alpha 1-microglobulinuria is a significant predictor of BEN vs. other kidney diseases. CONCLUSION: Danilovic's criteria enabled a diagnosis of BEN only in chronic renal failure and differential diagnosis between BEN and healthy persons but not between BEN and other kidney diseases. Out of the examined indices of proximal tubular disorders, only alpha 1-microglobulinuria significantly discriminated BEN from other kidney diseases.     

Prevalence of Balkan endemic nephropathy has not changed since 1971 in the Kolubara region in Serbia

BACKGROUND/AIMS: Thirty-one years after the first cross-sectional study, the population of Vreoci, a Balkan endemic nephropathy (BEN) village, was reinvestigated in order to determine the current prevalence of BEN and the clinical and laboratory characteristics of BEN family members with detected signs of kidney disease. METHODS: A total of 2,009 inhabitants (82% of the adult population) of the village were examined. Danilovic's criteria were used for diagnosis and classification of BEN. RESULTS: The prevalence of BEN (1.70%) was similar to that in 1971 (1.67%). Diagnosis of BEN was established in 19 BEN family members, suspected BEN in 23, proteinuria in 29, while 16 healthy members were examined as controls. Urine protein, alpha1-microglobulin levels and frequency of glucosuria were significantly higher and kidney length significantly smaller in the three patient groups than in healthy persons. Serum urea and creatinine levels were significantly higher, but creatinine clearance was lower in BEN and BEN suspected patients than in the other two groups. CONCLUSION: The prevalence of BEN remains stable over time in Vreoci village. Manifested disease was found in both BEN and BEN suspected patients. In persons with proteinuria but not enough criteria for BEN, tubular disorders and hypertension were frequently found.     

Detection of renal dysfunctions in family members of patients with Balkan endemic nephropathy

BACKGROUND/AIM: Recent studies have questioned whether new cases of Balkan endemic nephropathy (BEN) are occurring. The aim of the present study was to find out whether new members with renal dysfunctions can be identified among family members of BEN patients from the Kolubara region. METHODS: The study included 47 family members of 5 BEN patients on hemodialysis (HD) and 17 members of 3 non-BEN patients on HD. Their medical and epidemiological histories were taken, an objective survey made, and all persons were examined for global and tubular kidney function. RESULTS: Seven BEN family members (2 with previously known BEN) had creatinine clearance (Ccr) below the 75th percentile rank according to sex and age. All non-BEN family members had normal Ccr and no evidence of previous renal disorders. Hypertension was found in 20 (43%) BEN and 6 (35%) non-BEN family members. No significant differences in the frequency of renal function disorders (proteinuria, alpha1-microglobulinuria, urine specific gravity, osmolality, functional excretion of sodium, tubular phosphate resorption) or anemia were found between the groups. Renal disorders were detected in 18 BEN family members without previously detected disease, 3 of whom fulfilled criteria for a diagnosis of BEN and another 2 for BEN-suspected persons. CONCLUSION: New cases of BEN are still arising among the affected families in the Kolubara region.     

Beta2-Microglobulin and Alpha1-Microglobulin as Markers of Balkan Endemic Nephropathy,a Worldwide Disease

Background:?Urine beta2-microglobulin (beta2-MG) was mainly used as a tubular marker of Balkan endemic nephropathy (BEN) but recently alpha1-microglobulin (alpha1-MG) was proposed for the diagnosis of BEN. In this study, the potential of urine beta2-MG, alpha1-MG, albumin, and total protein in the differentiation of BEN from healthy persons and patients with glomerulonephritis (GN) and nephrosclerosis (NS) was examined.?Methods:?This study involved 47 patients with BEN, 36 with GN, 11 with NS, 30 healthy subjects from BEN families, and 46 healthy subjects from non-BEN families.?Results:?In BEN patients area under the curve (AUC) for urine beta2-MG (0.828) and alpha1-MG (0.782) was higher than for urine albumin (0.740), but in GN patients AUC for urine protein (0.854) and albumin (0.872) was significantly higher than for the two low molecular weight proteins. AUC for all four urinary markers in NS patients was significantly lower than in BEN patients, ranging between 500 and 595. Median urine beta2-MG excretion in BEN patients was 17.5 times higher than in GN patients and 18.3 times higher than in controls; median alpha1-MG excretion was higher only 3.0 and 2.25 times, respectively. In the differentiation of BEN from healthy controls, beta2-MG had higher sensitivity and specificity at the cutoff levels (p < 0.001) than alpha1-MG (p < 0.05). In the differentiation of BEN from GN, beta2-MG was the best marker.?Conclusion:?All four urinary markers can be used for the differential diagnosis of BEN, beta2-MG being the best. Like in aristolochic acid nephropathy, beta2-MG seems to be an early marker of tubular damage in BEN.     

Proteinuria and beta 2-microglobulinuria in patients with tumors of the renal pelvis and ureter and in healthy persons from areas of endemic nephropathy

Total proteinuria (SSA test) and beta-2-microglobulinuria (radial immunodiffusion and radioimmunoassay tests) were measured in 60 rural patients with histologically proven tumors of the renal pelvis and ureters and as many individually matched controls. The controls were the first neighbours of the same sex, age (+/- 2 yrs), profession and migratory history. Urinalysis was performed twice with an interval of nine years (in 1973/4 and 1982/3). As expected, both proteinuria and beta-2-microglobulinuria were more frequently elevated among the patients. However, these tests were very often positive among the controls as well. Thus, the prevalence rate of hyper-beta-2-microglobulinuria, as measured by the RIA method in 1982/3, was 26.3% in the control group. A high frequency of the tubular damage, as revealed by this test, among presumably healthy persons has been attributed to the fact that most upper urothelial tumor cases come from the Balkan endemic nephropathy foci where a significant proportion of inhabitants show signs of kidney affection.     

Creatinine clearance and kidney size in Balkan endemic nephropathy patients

BACKGROUND/AIMS: Symmetrically shrunken kidneys have been considered as one of the characteristics of Balkan endemic nephropathy (BEN), but there is no agreement when the shrinking does occur in the course of the disease. In the present study, the relation between creatinine clearance (Ccr) and kidney length was compared between the patients in the early phase of BEN and other renal diseases. METHODS: The study included 84 patients with BEN (39 males, aged 54 +/- 12 years), 31 patients with other renal diseases (15 males, aged 54 +/- 14 years) and 15 healthy subjects as controls. Only the patients with Ccr above 90 ml/min were included into the study. The kidney length was measured by sonography using sector sound of 3.5 MHz. RESULTS: In healthy controls and patients with renal disease other than BEN, Ccr varied between 90 and 177 ml/min, and only 3 patients had Ccr above 150 ml/min. On the contrary, 15 (18%) BEN patients had Ccr between 90 and 120 ml/min, and 37 (44%) BEN patients had Ccr above 150 ml/min. Sonographically measured kidney length of all healthy subjects and patients with renal diseases other than BEN was above 10.5 cm. Out of 84 BEN patients, 21 (25%) patients had kidney length less than 10.5 cm. CONCLUSION: BEN patients in the early phase of the disease had significantly higher Ccr and smaller kidney in comparison to the patients with other renal diseases.     

Balkan Endemic Nephropathy is Still Present in the Kolubara Region,Serbia

Background. Almost 50 years ago Balkan Endemic Nephropathy (BEN) was first described in Serbia in the village of ?opi? where the first field examination was carried out in 1971. Our aim was to find out whether BEN is still present in this region. Methods. Prevalence data on BEN from a field examination run in 1971 were compared with the results of a cross-sectional study conducted in the same village in 1992. In addition, every new case of the disease diagnosed between 1971 and 1992 was recorded retrospectively. The prospective study included 50 members of five BEN families randomly selected from 28 BEN families registered in the village ?opi? in 1992. The objective survey and examination of global and tubular kidney function was carried out in all examined persons once yearly in 1998, 1999, and 2000. Results. The overall prevalence of BEN was 6.4% in 1971 and 8.9% in 1992. In the period of 21 years, 161 new BEN patients were detected in 28 families in which the disease had already been recorded. No new family affected by BEN and none of the new patients in 47 families registered previously as nonaffected were discovered. In the prospective study of five BEN families, three new BEN cases were discovered among 50 members, and two patients fulfilled criteria for BEN-suspected ones. Conclusion. Balkan Endemic Nephropathy (BEN) is still present in the village of ?opi?, but the clinical course of the disease became more protracted over time. New cases of BEN appeared only in the affected families.     

How common is Balkan endemic nephropathy among immigrants in endemic regions?

Purpose

In the early 1970s, a number of authors described the development of Balkan endemic nephropathy (BEN) in immigrants in endemic regions. The aim of this study was to examine whether immigrants in endemic regions are suffering from BEN today.

Methods

The study involved 193 residents of two endemic regions divided into three groups: two groups of native residents—(1) members of BEN families, (2) members of non-BEN families, and (3) immigrants, who had moved from non-affected settlements to the endemic regions of Kolubara (38 years ago) or Semberia (20 years ago). All persons were subjected to an interview, objective examination, kidney ultrasound, and laboratory analysis to detect the presence of BEN consensus diagnostic criteria.

Results

The number of immigrants with BEN biomarkers outside cutoff values was significantly lower than for BEN family members. Five BEN family members met diagnostic criteria for BEN and four for suspected BEN. Although five non-BEN family members had different combinations of BEN biomarkers, all of them had diseases other than BEN in which these biomarkers also occurred. None of the immigrants met the criteria for BEN. Nevertheless, one descendant of an immigrant, a 78-year-old male, whose mother was from a non-BEN family in the Kolubara district, exhibited all the criteria for BEN: alpha1-microglobulinuria, chronic renal failure, and anemia.

Conclusion

While 30 years ago, BEN was reported equally among immigrants and natives, currently it is diagnosed in some BEN family members in the eighth decade of life, but extremely rarely in immigrants also in old age.

     

Balkan endemic nephropathy is still present in the Kolubara region, Serbia

BACKGROUND: Almost 50 years ago Balkan Endemic Nephropathy (BEN) was first described in Serbia in the village of Sopi? where the first field examination was carried out in 1971. Our aim was to find out whether BEN is still present in this region. METHODS: Prevalence data on BEN from a field examination run in 1971 were compared with the results of a cross-sectional study conducted in the same village in 1992. In addition, every new case of the disease diagnosed between 1971 and 1992 was recorded retrospectively. The prospective study included 50 members of five BEN families randomly selected from 28 BEN families registered in the village Sopi? in 1992. The objective survey and examination of global and tubular kidney function was carried out in all examined persons once yearly in 1998, 1999, and 2000. RESULTS: The overall prevalence of BEN was 6.4% in 1971 and 8.9% in 1992. In the period of 21 years, 161 new BEN patients were detected in 28 families in which the disease had already been recorded. No new family affected by BEN and none of the new patients in 47 families registered previously as nonaffected were discovered. In the prospective study of five BEN families, three new BEN cases were discovered among 50 members, and two patients fulfilled criteria for BEN-suspected ones. CONCLUSION: Balkan Endemic Nephropathy (BEN) is still present in the village of Sopi?, but the clinical course of the disease became more protracted over time. New cases of BEN appeared only in the affected families.     

Hemodialysis Treatment in Patients with Balkan Endemic Nephropathy: An Epidemiological Study

Aim. To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. Methods. A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. Results. Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004–2006) The mean survival time of BEN males was 4.70 (95% CI 3.66–5.75) and for females was 5.02 (95% CI 1.47–4.53). Difference between males and females was not statistically significant (log rank 0.14, p?=?0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97–5.70) in BEN patients and 3.1 (95% CI 2.78–3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p?=?0.0038, P < 0.01). Conclusion. The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Survival of Balkan endemic nephropathy patients

The retrospective cohort study comprised 97 Balkan endemic nephropathy (BEN) and BEN-suspected patients discovered in 1971 in the field examination in the village of Sopi?, one of the regions most frequently affected by the disease. Our aim was to determine the outcome of the disease in patients and to compare the survival of BEN-suspected and BEN-manifested patients and the survival of their kidneys. The mean survival time was 16.4 years for all patients (95% CI 14.51-18.21) and 23.1 years for suspected and 13.3 years for manifested patients (log-rank = 19.46; d.f. = 1; p < 0.001). According to our results, it can be concluded that BEN is characterized by slow course and prolonged evolution and that the prognosis was consistently better for BEN-suspected than for BEN-manifested patients.     

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy,a worldwide disease

Abstract

Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. Methods: Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74?yr (53–87) and 73?yr (66–83) in controls. Results: In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2?µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6?mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80?pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90?pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0?pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5?pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. Conclusion: Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.     

Reliability of different expert systems for profiling proteinuria in children with kidney diseases

This study was designed to compare three urinary protein expert systems for profiling proteinuria in children with kidney diseases. Freshly voided urine specimens were collected from 61 children with glomerular diseases, 19 children with tubular diseases and 25 healthy children aged 3–16 years. The urinary protein expert systems were: (1) albumin/total protein ratio (APR), (2) α-1-microglobulin/α-1-microglobulin + albumin algorithm (AAA), and (3) the complex urine protein expert system (UPES, PROTIS) algorithm. APR correctly identified glomerular proteinuria in 47/61 children, tubular proteinuria in 16/19 children and normal proteinuria in 23/25 healthy children. AAA correctly identified glomerular proteinuria in 61/61 children and tubular proteinuria in 18/19 children, and 25/25 healthy children were characterized as having no abnormal proteinuria. AAA was not influenced by the stage of chronic kidney disease. UPES differentiated the type of proteinuria in children with glomerular diseases into glomerular (50/61 patients) and mixed glomerulo-tubular (6/61 patients). Tubular proteinuria was identified in 16/19 patients and described as mixed glomerulo-tubular proteinuria in 3/19 patients. Mixed glomerulo-tubular proteinuria was found only in children with chronic kidney disease stages 2–5 of glomerular and tubular diseases. In conclusion, the AAA and UPES had the highest accuracy levels.     

Studies of the analysis of urinary proteins from children with renal diseases by reversed-phase high performance liquid chromatography]

In order to analyze urinary proteins from patients with various renal diseases, a reversed-phase high performance liquid chromatography (HPLC) with IPG PACK ODS column packed with polyporous glass was used. The reproducibility of standard proteins was good. The results by this method correlated well with those by radioimmunoassay or laser nephelometry, precolumn procedure needed the centrifugation only. The reversed-phase HPLC was superior to the other HPLC methods in the analysis of urinary proteins for its simplicity and high sensitivity. The peaks of both alpha 1-acid glycoprotein (alpha 1-AGP) and human serum albumin (HSA) in the chromatogram was regarded as the marker of renal damage. Urinary alpha 1-AGP/HSA ratio was calculated after measuring these two peak areas. As a result, it was significantly higher in the urine from patients with various glomerulonephritis (GN) than in those from healthy children. In the patients with postural proteinuria, it was the same level as that in healthy children. These date suggest that the urinary alpha 1-AGP/HSA ratio would be a beneficial indicator to find out the patients with GN from among children with proteinuria. Furthermore, it seems that this method is suitable for use in routine screening of renal diseases for its simplicity and speed.     

Acute effects of acetaminophen on renal function and urinary excretion of some proteins and enzymes in patients with kidney disease.

The acute effects of acetaminophen, a commonly used as analgesic drug, upon the urinary excretion of some proteins and enzymes as markers of kidney damage, was investigated. Patients with chronic glomerulonephritis (GN) and Balkan endemic nephropathy (BEN), having kidney vulnerable to toxic drugs, were enrolled in the study. Timed urine specimens were collected: before drug administration, and in 3-hour periods for 24 hours after an oral dose of 2 g of acetaminophen. Urinary excretion of albumin before acetaminophen treatment was significantly higher in patients with GN and BEN than in healthy adults, however, beta 2-microglobulin excretion was increased in BEN patients only. Urinary excretion of creatinine markedly increased immediately after acetaminophen ingestion. Urinary excretion of total protein and albumin was not changed after acetaminophen administration. However, acetaminophen treatment produced a significant increase in beta 2-microglobulin excretion in patient with BEN and GN, and in clinically healthy members of nephropathic families. Excretion of aminopeptidase N (APN) activity before acetaminophen treatment was significantly higher in patients with GN, however, NAGA excretion was higher in both GN and BEN patients than in healthy controls. After acetaminophen administration urinary excretion of APN, dipeptidylpeptidase IV (DPP IV), gamma-glutamyltranspeptidase (GGT) and N-acetyl-beta-D-glucosaminidase (NAGA) did not increase significantly in any group studied. This study has shown that urinary excretion of APN, DPP IV, NAGA and GGT, as markers of kidney brush border and lysosomal damage, did not change after 2 g of acetaminophen taken orally. beta 2-microglobulin was a marker of acute acetaminophen nephrotoxicity in kidney disease patients and in clinically healthy adults from nephropathic families.     

Hemodialysis treatment in patients with Balkan endemic nephropathy: an epidemiological study

AIM: To analyze hemodialysis (HD) treatment of patients with Balkan endemic nephropathy (BEN) from five endemic villages in the South Morava Region of Serbia. Analyses of patterns of incidence may generate hypotheses about the underlying causes of BEN, and prevalence data provide information on the current and likely future burden on health services for managing BEN. METHODS: A total of 143 end-stage kidney disease patients (ESKD) with BEN were admitted to the renal replacement program from 1974 to 2004: 121 to HD, 15 peritoneal dialysis, and 7 kidney transplantation. As a control group, 117 patients with other kidney disease (chronic pyelonephritis, glomerulonephritis, and ischemic nephropathy) admitted to HD at the time of BEN patients and matched by age and gender were studied. RESULTS: Most of the BEN patients (93.4%) treated by HD were born from 1917 to 1941. The majority of patients (79.3%) started HD from 1977 to 1991 (period of 15 years). The mean age of BEN patients starting HD treatment was 49.1 years in the period from 1974 to 1978, and increased steadily in the following years, being 72.5 years in the last period of study (2004-2006) The mean survival time of BEN males was 4.70 (95% CI 3.66-5.75) and for females was 5.02 (95% CI 1.47-4.53). Difference between males and females was not statistically significant (log rank 0.14, p = 0.7, P > 0.5). Mean survival times of 4.84 (95% CI 3.97-5.70) in BEN patients and 3.1 (95% CI 2.78-3.84) in other kidney disease patients were found. Difference between BEN patients and controls was statistically significant (log rank 8.38, p = 0.0038, P < 0.01). CONCLUSION: The population of endemic villages around the South Morava River admitted to HD treatment after 1974 was exposed to environmental toxicant(s) from 1917 to 1941. The most intense effect of environmental exposure was in that period, with ESKD in patients in their forties. The exposure to environmental toxicants has diminished, so ESKD of BEN has become less frequent and manifested in the older age, mean 72.5 in the period from 2004 to 2006. Different type of exposure was registered in some other endemic regions in Serbia and abroad.     

Urinary protein patterns in patients with Balkan endemic nephropathy

Purpose

Urinary excretion of beta2-microglobulin (beta2-MG), albumin, immunoglobulin G (IgG) and protein was examined in patients with Balkan endemic nephropathy (BEN), glomerulonephritis (GN) and healthy controls.

Methods

The proteins were measured in morning urine samples from 74 patients with BEN, 50 healthy persons and 22 patients with GN.

Results

In BEN patients, median values for albumin, beta2-MG and protein were above upper normal limits, but median IgG was inside normal range. All patients with GN had microalbuminuria (MAU) and half of them had increased urinary beta2-MG, which was also found in eleven patients with increased urinary IgG. In BEN patients, there were significant negative correlations between eGFR and all measured urinary proteins, the composition of which changed during the course of BEN. In patients with eGFR > 60 ml/min/1.73 m² isolated beta2-MG was the most frequent finding (10/12 patients), but MAU was present in 4/12 patients. In BEN patients with eGFR between 30 and 59 ml/min/1.73 m², beta2-MG appeared as often as the combination of beta2-MG and albumin and isolated MAU. Out of 49 BEN patients with eGFR > 30 ml/min/1.73 m² 15 had increased urinary IgG either alone (1) or together with beta2-MG (3) or albumin (3) or beta2-MG and albumin (8). In BEN patients with GFR < 30 ml/min/1.73 m² only 1/25 had isolated beta2-MG but increased urinary IgG with increased beta2-MG, and albumin was the most frequent.

Conclusion

Although low-molecular weight proteinuria was the most frequent urinary finding in BEN patients, MAU was frequently detected in advanced stages of BEN but also in some patients with eGFR > 60 ml/min/1.73 m². IgG was increasingly found as eGFR decreased.     

Endothelin Receptors in the Kidney of Patients with Proteinuric and Non-Proteinuric Nephropathies

Background. Endothelin-1 (ET-1), which acts via the specific receptors ET-A and ET-B, has been implicated in the development of renal scarring. The activation of the endothelin system was observed in experimental models of glomerular diseases and was attributed to the toxic action of proteinuria on the tubular epithelial cells. The aim of this study was to investigate whether the endothelin system in the kidney is altered in glomerular diseases and possibly related to proteinuria. Methods. Thirty-seven patients with different types of glomerulonephritis and 14 controls were included. Patients presented either nephrotic syndrome (n=25) or mild proteinuria (<1g/24h, n=12). The expression of ET-A and ET-B receptors in the renal tissue was examined immunohistochemically. At the time of biopsy, urinary ET-1 was determined. Results. Both receptors were mainly localized within tubular epithelial cells, and their expression was significantly higher in patients with glomerulonephritis compared to controls. The expression of ET-B was higher in nephrotic compared to non-nephrotic patients, while no difference was observed in the expression of ET-A receptors. A significant positive correlation of the degree of proteinuria with the excreted ET-1 (r= 0.487, p<0.05) and the extent of immunostaining for ET-B receptors (r=0.420, p<0.05) was observed. The expression of ET-B receptors and the excretion of ET-1 decreased significantly in patients with remission of nephrotic syndrome after therapy. Conclusion. This study provides evidence that the endothelin system is activated in human glomerular disease, confirming data from experimental studies. Proteinuria seems to be related to the activation of endothelin system, though further investigation is necessary to clarify this issue.     

Urinary excretion of dipeptidyl aminopeptidase i.v. in patients with renal diseases

Enzymuria is a frequent finding in patients suffering from various kidney diseases. The present study was undertaken to evaluate the clinical value of the determination of tubule-brush-border-associated dipeptidyl aminopeptidase IV (DAP IV) in the urine of patients with acute and chronic tubulointerstitial nephritis (n = 12), chronic glomerulonephritis (n = 15), essential arterial hypertension (n = 30), after kidney transplantation (n = 20), and of healthy control persons (n = 68). DAP IV was measured in spontaneously voided mid-stream morning urine ("second morning urine"), and was expressed as enzyme activity in units/liter. In order to account for variations due to urine concentration without collecting 24-hour specimens, a urinary DAP IV/creatinine ratio (DCR) was calculated. Furthermore, patterns of proteinuria were assayed by SDS-polyacrylamide gel electrophoresis. Urinary DAP IV activity of healthy controls was 4.94 +/- 0.12 U/l (DCR: 0.46 +/- 0.30 U/mmol creatinine) with only small day to day variations. Urinary DAP IV activity in patients with tubulointerstitial nephritis was significantly higher (15.5 +/- 15.6 U/l, p less than 0.05 vs controls; DCR: 1.67 +/- 0.97 U/mmol creatinine, p less than 0.001 vs controls). In patients with chronic glomerulonephritis urinary DAP IV activity was 9.6 +/- 5.6 U/l, p less than 0.05 (DCR: 1.22 +/- 0.75 U/mmol creatinine, p less than 0.05 vs controls). Increased urinary DAP IV activity in patients with chronic glomerulonephritis was associated with a mixed glomerulo-tubular pattern of proteinuria (as determined by SDS-PAGE).(ABSTRACT TRUNCATED AT 250 WORDS)     

成纤维细胞生长因子23与慢性肾脏病中晚期患者冠状动脉钙化的关系

目的 探讨慢性肾脏病（CKD）中晚期患者血成纤维细胞生长因子23（FGF23）水平与冠状动脉钙化的关系。 方法 2010年4月至12月我院肾脏科病房、腹透中心、血透中心的CKD非透析（CKD 3~5期）、腹膜透析和血液透析患者共150例为对象;年龄、性别匹配的25例健康体检者为对照。收集患者临床和相关生化指标资料。采用酶联免疫法测定血清全段FGF23水平。对入选患者进行冠脉多层螺旋CT（MSCT）检查。分析FGF23水平与CKD中晚期患者冠脉钙化的关系。 结果 CKD中晚期患者血清FGF23水平显著高于健康对照组[196.46（83.09,355.02） ng/L比27.17（21.63,51.20） ng/L,P < 0.01];透析患者的FGF23水平显著高于非透析患者（P < 0.01）;血透患者的FGF23水平显著高于腹透患者[6048.29 （1129.08,34807.45） ng/L比1625.80（602.83,7521.78） ng/L,P < 0.01]。CKD中晚期患者冠脉钙化发生率较高（74/130,56.9%）,血清FGF23水平与冠脉钙化分数（CaS）呈正相关（r = 0.177,P < 0.05）。Logistic回归分析显示年龄（β = 0.091,OR = 1.095,P < 0.01）、透析龄（β = 2.013,OR = 7.483,P < 0.05）和FGF23水平（β = 0.838,OR = 2.311,P < 0.05）是CKD中晚期患者发生冠脉钙化的独立危险因素。冠状动脉钙化的ROC曲线显示,FGF23曲线下面积为0.705（P < 0.01）,当检测的截点为786.73 ng/L时,其敏感度和特异性分别为62.5%和75.9%;碱性磷酸酶（AKP）的曲线下面积为0.626（P = 0.017）,当检测的截点为79.75 U/L时,其敏感度和特异性分别为84.5%和41.5%。血磷在诊断冠脉钙化时没有统计学意义。 结论 血清FGF23水平与CKD中晚期患者冠脉钙化发生相关。FGF23作为诊断冠脉钙化的参考指标,其敏感度低于AKP,特异性优于AKP。