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.

     

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.     

Morphology of Balkan endemic nephropathy: current state

Balkan endemic nephropathy (BEN) is interesting renal disease, because of its unique clinical, epidemiological and morphological characteristics: intensive interstitial fibrosis and tubular atrophy without any inflammation. In the present paper we evaluate the incidence of BEN from the morphological point of view for the last decade. Therefore we analyzed material obtained from autopsies, kidney biopsies and nephrectomy due to upper urothelial cancer (UUC) from the patients which were divided into two groups: those with permanent residence in BEN areas and those from nonendemic areas. At the Institute of Pathology, University of Belgrade for the last 15 years we had only 1 autopsy due to BEN out of 6,825. More than 30 years ago there were over 50 autopsy cases of BEN at the same institute. For the last decade we had only 2 kidney biopsies suspected for BEN out of 2,182, but morphologically not confirmed as BEN. However, previously we had over 40 kidney biopsies diagnosed as early or late stage of BEN. At the Clinical Center of Serbia 180 nephrectomies were performed due to UUC. The incidence of UUC for the last five years in BEN regions has significantly decreased, whereas at the same time in non-BEN regions it has remained on the same level. There was no morphological difference of the renal tissue adjacent to tumor between patients from BEN and non-BEN regions. According to our study based on routine pathological work, we could clearly conclude that BEN today is more clinical and epidemiological than a morphological entity.     

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.     

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.     

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.     

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.     

Clinical markers in adult offspring of families with and without Balkan Endemic Nephropathy

Balkan Endemic Nephropathy (BEN) is a kidney disease that progresses slowly. Only a few studies have investigated renal clinical markers in offspring of BEN families before the onset of the disease. This project aimed to determine whether kidney function and structure are altered in BEN offspring compared with non-BEN offspring. The study population consisted of 102 adult BEN offspring and a control group of 99 non-BEN offspring. We collected urine and blood samples, and conducted face-to-face interviews, physical examinations and ultrasound measurements of the kidney. Total protein, albumin, beta2-microglobulin and creatinine in urine, creatinine and urea in serum, and creatinine clearance (CCR) were determined. Two risk factors were assessed: first, the overall status of being an offspring from a BEN family, and second, the specific status of a mother and/or father with BEN. The data were analyzed using linear regression. After adjusting for confounders, we found that kidney length and minimal cortex width in BEN offspring were significantly decreased. Urine concentrations of total protein, albumin, and beta2-microglobulin were higher in BEN offspring. Regarding parental history, the associations were statistically significant only for the offspring of mothers who had BEN, with the exception of minimal cortex width, which showed no parental difference. For CCR, we did not identify a statistically significant effect for BEN offspring status nor for parental history. In conclusion, adult offspring of BEN families can be characterized by shorter kidney length and an increased excretion of albumin, total protein, and beta2-microglobulin, in particular, when the mother had BEN.     

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.     

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.     

Elevated tumour markers in patients with Balkan endemic nephropathy

Balkan nephropathy (BEN) is commonly associated with urothelial cancer. Urothelial cancer is manifested in the advanced stage of disease. The aim of this study was to facilitate early detection of urothelial cancer in BEN patients and their family members living in an endemic region by using tumour markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and a putative marker, ferritin. Fifteen BEN patients with normal renal function, 17 with renal failure (BEN-RF), 13 healthy members of their families (HFM), 14 patients with glomerulonephritis (GN) and 12 healthy controls (C) were studied. Serum CEA levels in BEN patients were within normal limits, however, in BEN-RF patients they were significantly increased over HFM (p<0.05). Serum TPA levels in BEN and BEN-RF patients were significantly higher than in the C and HFM groups (p<0.05). Urinary CEA was not significantly different between the groups studied. Urinary TPA levels in HFM (median 125 U/1, BEN (236 U/l) and BEN-RF (275 U/l) were significantly increased over C (30 U/l), however, TPA levels were increased also in GN patients (437 U/l). None of the BEN patients studied developed urothelial cancer during the ten years' follow-up. Markedly elevated urinary TPA-like levels in all patients studied (HFM, BEN, BEN-RF, GN) suggest that urinary TPA may not be a reliable tumour marker. However, the clinical relevance of high TPA levels in BEN patients should be evaluated.     

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.     

Identification of Fabry's disease by the screening of alpha-galactosidase A activity in male and female hemodialysis patients

BACKGROUND: Although previous studies reported that the prevalence of Fabry's disease was 0.16 - 1.2% in hemodialysis (HD) patients based on measurement of a-galactosidase A (alpha-Gal A) activity, few reports detected female patients by the screening for alpha-Gal A. Here we determined the prevalence of Fabry's disease not only in male but also in female HD patients by measuring alpha-Gal A. METHODS: Plasma alpha-Gal A was measured in 696 consecutive males (n = 401) and females (n = 295) on HD. Patients with low plasma alpha-Gal A were examined for leukocyte alpha-Gal A, and patients with low leukocyte alpha-Gal A underwent alpha-Gal A gene sequence analysis for possible mutations, and family survey. RESULTS: Among 15 patients with low plasma alpha-Gal A activity, 4 male patients with low leukocyte alpha-Gal A and 1 female patient revealing low plasma alpha-Gal A were detected in 696 HD patients (0.7% of total patients). 3 of these 5 patients were already diagnosed to have the classical type of Fabry's disease. The other 2 patients were newly diagnosed as Fabry's disease, and did not have typical manifestations of Fabry's disease other than renal failure and left ventricular hypertrophy. DNA analysis of these 2 newly diagnosed patients revealed that each had an alpha-Gal missense mutation, previously identified (E66Q, M2961). CONCLUSION: Fabry's disease should be considered in the etiology of unexplained end-stage renal disease. Not only affected males but also affected females undergoing HD patients can be readily diagnosed by alpha-Gal A activities and gene analysis. These patients and their family members may benefit from enzyme replacement therapy for Fabry's disease.     

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.     

Hypouricemia due to increased tubular urate secretion

A 45-year-old woman had hypouricemia (serum uric acid, 1.0-2.3 mg/dl) with increased uric acid clearance (29.8 +/- 9.3 ml/min/1.73 m2). Uric acid clearance to creatinine clearance ratio (Cua/Ccr) was suppressed markedly by pyrazinamide to 2.3% and surprisingly enhanced by probenecid to 227.8%. No other renal tubular or metabolic abnormalities were detected. This previously unreported high postprobenecid Cua/Ccr suggests that markedly increased urate secretion by the renal tubule is responsible for hypouricemia in this patient.     

Identification of NQO1 and GSTs genotype frequencies in Bulgarian patients with Balkan endemic nephropathy

BACKGROUND: Polymorphisms in NAD[P]H:quinone oxidoreductase (NQO1) and glutathione S-transferases (GSTs) have been reported to be associated with an increased risk for environmentally and/or occupationally induced renal and bladder cancers. Genetic factors related to chronic nephropathy and to urinary bladder or renal cancer development in Balkan endemic nephropathy (BEN) is unknown. In order to evaluate their possible role in BEN susceptibility, we determined the frequencies of NQO1 alleles *1, *2 and *3, as well as the GSTT1 and GSTM1 null genotypes in BEN patients and healthy subjects from a non-endemic region of Bulgaria. METHODS: The respective genotypes of 95 unrelated Bulgarian BEN patients and of 112 healthy individuals (control group) were determined by rapid cycle polymerase chain reaction (PCR) and detected with either SYBR green I fluorescent dye or melting curve analysis using allele specific probes. RESULTS: NQO1 genotyping showed a higher NQO1*2 allele frequency (23.68%) in BEN patients compared to controls (18.75%; p=0.219), while NQO1*3 allele frequencies were similar in both groups (2.63% in BEN patients vs. 2.23% in controls; p=0.791). The GSTT1 deficiencywas observed in 20% of BEN patients vs. 16.1% of controls (p=0.613). The GSTM1 null genotype was found in 45.3% of BEN patients vs. 51.8% of controls (p=0.674). There was no influence of NQO1 and GSTs genotypes found on BEN risk. CONCLUSIONS: Our results established that alleles NQO1*2 and NQO1*3, as well as lack of GSTT1 and GSTM1 did not influence the BEN risk. These findings provide novel information on the genetic heterogeneity in the healthy Bulgarian population.     

长期腹膜透析患者转归临床分析

目的研究长期腹透患者临床转归,分析其临床特点。方法对本院1994年1月至2003年8月腹透龄超过3年以上的58例腹透患者进行分析。根据其临床转归分为继续腹透组、转向移植组、转向血透组及死亡组。比较各组间近期营养指标（半年以内血清白蛋白水平）、近期透析充分性指标（Kt／V、Ccr）、水清除指标及残肾功能等临床特点。对死亡组同时做回顾性前后自身对照研究（死亡前半年以内与死亡前1年资料比较）。对继续腹透组回顾性分析比较1年前资料,并前瞻性追踪随访1年。结果死亡组总Kt／V显著低于其余3组（P〈0．05）;总Ccr显著低于继续腹透组（P〈0．01）。继续腹透组、移植组及血透组3组间总Kt／V、总Cer及血清白蛋白水平差异无统计学意义。血透组水清除指标显著低于继续腹透组及移植组;继续腹透组水清除指标稍高于死亡组但无显著性差异。死亡组近期总Kt／V显著低于死亡前1年总Kt／V（P〈0．05）;近期总Ccr显著低于死亡前1年总Ccr（P〈0．01）。继续腹透组近期总Kt／V及总Ccr与1年前及1年后指标比较差异均无统计学意义,但残肾Kt／V或残肾Ccr随时间推移而显著下降（P〈0．05）。继续腹透组残肾Kt／V或残肾Ccr显著高于死亡组及血透组（P〈0．05）。死亡组血清白蛋白水平较其余3组降低但差异无统计学意义。死亡组13例中有7例死于心脑血管疾病。结论腹透3年以上患者大部分仍可继续腹透。透析不充分是长期腹透患者死亡的重要原因。死亡的病因主要为心脑血管疾病。残肾功能可影响长期腹透患者的转归。     

Prognostic prediction of long-term clinical courses in individual IgA nephropathy patients

Summary: This study was performed to evaluate predictive factors determining a long-term prognosis in individual IgA nephropathy patients. One hundred and fifty-five patients who have been continuously followed up for 10 years or more from the first renal biopsy in our renal unit were the subjects of this study. As predictive factors, initial proteinuria, initial creatinine clearance (Ccr) values, initial hypertension, histological severity (eight parameters and total score), persistence of massive proteinuria (% duration of massive proteinuria; % DP) and persistence of hypertension were evaluated. All 25 of the 155 patients who had either high total score of 17 or more, or less than 60 mL/min in initial Ccr values, went onto haemodialysis (HD). However, all 38 patients who had TS of 4 or less did not. The remaining 95 patients who showed both total score from 5 to16 and Ccr values of 60 mL/min or more were divided into two groups: HD group (32 cases) and non-HD group (63 cases). All patients but one in the HD group showed 30% or more in %DP, and 50 of 63 patients in the non-HD group snowed 30% or less (P < 0.001). Multivariate analysis using a logistic model of factors associated with prognosis indicating HD revealed that %DP was the highest relative risk (19.5) compared with interstitial fibrosis (10.2), initial Ccr values (6.8), persistent hypertension (4.2) and initial proteinuria (1.4). These results indicated that the most reliable, independent factor determining a long-term individual prognosis is persistent massive proteinuria of 1.0 g/day or more.     

Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease

This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion.     

Hypouricemia due to subtotal defect in the urate transport

Hypouricemia due to renal tubular defects is rarely reported. We report here our observations of two such patients who cannot be classified into any of the previously reported categories of renal hypouricemia. They showed no suppression of urate clearance to creatinine clearance ratio (Cua/Ccr) following the administration of pyrazinamide, and no increase of Cua/Ccr after probenecid. It is tempting to speculate upon the subtotal defect in the urate transport as a condition explaining the above results.