The association between serum uric acid and renal damage in a community-based population: the Takahata study

Background

Hyperuricemia is a risk factor for end-stage renal disease. This study examined the association between serum uric acid and renal damage in a community-based population.

Methods

In this study 3126 subjects without renal insufficiency were recruited at baseline and were followed for one year. The urinary albumin–creatinine ratio (UACR) and β₂-microglobulin–creatinine ratio (UBCR) in morning spot urine samples were used as indices of either glomerular (UACR) or tubular (UBCR) damage.

Results

The mean value of serum uric acid (mg/dL) was 5.8 ± 1.3 (SD) in men and 4.5 ± 1.1 in women. In cross-sectional analysis the increased serum uric acid levels were accompanied by higher UACR values in both men and women (P < 0.01). In contrast, UBCR values were reduced when uric acid levels increased in both men and women (P < 0.01). Multivariate analysis revealed that albuminuria (UACR ≥ 30 mg/g) was significantly associated with increased uric acid (≥7 mg/dL for men, ≥6 mg/dL for women). High UBCR (≥300 μg/g) was negatively associated with uric acid in men, but not in women, after adjustment for possible confounders. In longitudinal analysis in 1388 subjects multiple linear regression analysis showed that uric acid at baseline was an independent factor for one-year increase of UACR [coefficient 4.80 (95 % confidence interval 0.40–9.33) (mg/g) per 1 mg/dL increase in uric acid, P = 0.033].

Conclusion

This study showed that serum uric acid concentration was positively associated with UACR, suggesting that uric acid may be related to glomerular damage in a community-based population.     

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.     

Increased urinary albumin excretion in children from families with Balkan nephropathy

Balkan nephropathy (BN) has not been described in children. However, some previous studies have revealed abnormalities of the urinary tract in children from families with BN. In the present study, urinary excretion of albumin was studied in 703 healthy children, age 9-13 years, from endemic and non-endemic settlements around the South Morava River. Since BN is an environmentally induced disease, with possible seasonal variation of toxicant(s), children were studied three times a year: spring, autumn, and winter. After a water load of 15 ml/kg body weight, a 3-h urine sample was collected, from 7 to 10 a.m. Albumin excretion in urine was highest in children from families with BN in all three periods investigated. It was significantly different from excretion in children from the city, and in autumn it was also different ( P<0.01) from children in non-endemic families. Correlation analysis of albumin excretion with some urinary markers of tubular nephrotoxicity shows the highest correlation with both beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase in endemic villages in autumn. If the upper limit of albumin excretion is set at 8.5 mg/mmol creatinine, then in autumn increased albumin excretion was found in 15 of 229 children from endemic settlements and in only 5 of 454 children from non-endemic areas ( P<0.0001). Evidence is presented that in autumn children from families with BN excreted significantly more albumin than those from non-endemic families but living in the same settlements, or from children living outside of the endemic region in the city of Nis.     

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.     

The effect of bariatric surgery on renal function

BackgroundObesity is associated with albuminuria and impaired renal function. We previously reported on 38 nondiabetics with improved albuminuria after Roux-en-Y gastric bypass (RYGB).MethodsOur objectives were to evaluate changes in renal function, urinary albumin-to-creatinine ratio (UACR), and glomerular filtration rate (GFR) in a larger cohort of patients with normal or mildly impaired renal function, undergoing RYGB or sleeve gastrectomy at 1 year postop. This was a retrospective study. Inclusions: patients with preoperative and 1 year postoperative serum and urine albumin and creatinine and weight (kg). Exclusions: preop chronic kidney disease (CKD)≥Stage 3 or macroalbuminuria (UACR≥300 mg/g). Primary outcomes: changes in UACR and estimated GFR (eGFR) at 1 year. The setting was in a public hospital in New York City, 2004–2011.Results158 patients met inclusion criteria; 91.8% female; mean age 40.8 years; 84.2% white Hispanic, 14.6 % black. Hypertension was present in 43.0%, diabetes mellitus in 28.5%. UACR was 21.5±3.2 mg/g, decreasing to 10.2±1.2 mg/g at 1 year (P<.0001). Microalbuminuria was present in 22/158 patients (14%) preop, resolving in 82% at 1 year; pre- versus 1 year postop eGFR, 97.5±2.2 versus 87.1±2.0 mL/min (P<.0001). Hyperfiltration was present in 8.2% preop, decreasing to 4.4% 1 year postop.ConclusionIn this mainly female minority population, UACR decreased within the normal range, while eGFR decreased from normal to the range for Stage 2 CKD at 1 year postop. Microalbuminuria resolved in most affected and hyperfiltration resolved in nearly half of those affected. This study is limited by its retrospective nature. Prospective studies should be performed.     

Brachial–ankle pulse wave velocity is independently associated with urine albumin-to-creatinine ratio in a Chinese community-based cohort

Purpose

Arterial stiffness is important in the development of albuminuria. The brachial–ankle pulse wave velocity (baPWV) acts as an indicator of arterial stiffness and may be associated with cardiovascular disease morbidity and mortality. The urine albumin-to-creatinine ratio (UACR) is a metric used to diagnose albuminuria and has also been shown to be associated with cardiovascular disease. Here, we aim to elucidate the relationship between the baPWV and UACR in the Chinese community.

Methods

A community-based cohort of 3669 subjects was selected for the analysis. The BaPWV and UACR were measured from each subject. UACR ≥ 30 mg/g was defined as pathological albuminuria.

Results

The mean baPWV was 1536.59?±?305.89 cm/s, and the median UACR value was 6.11 mg/g (interquartile range 4.17, 10.68). A threshold-effect analysis was conducted, and the results showed that the cut-off value for the baPWV was 1269 cm/s. In subjects with baPWV values lower than 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria was not significantly associated with the baPWV (odds ratio 0.77, 95% confidence interval 0.57–1.03, P?=?0.08). However, in participants with baPWV ≥ 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria increased with increasing baPWV 100 cm/s (odds ratio 1.16, 95% confidence interval 1.11–1.22, P?<?0.001).

Conclusions

These findings suggest that, in this Chinese community-based cohort, elevated baPWV is independently associated with pathological albuminuria with a cut-off value of 1269 cm/s as determined by threshold-effect analysis.

     

Global and specific histone acetylation pattern in patients with Balkan endemic nephropathy,a worldwide disease

Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy present in the Danube river regions in several Balkan countries. There appears to be a polygenic susceptibility to the disease in interaction with multiple environmental factors (aristolochic acid, ochratoxin A). In a previous study SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs of BEN patients from Serbia and Bulgaria. Emerging connections between DNA methylation and histone acetylation prompted the present study on histone acetylation in patients with BEN. Methods: The study involved 39 patients with BEN, and 39 controls collected from non-endemic regions in Serbia. The EpiSeeker Histone H3 and H4 Total Acetylation Detection colorimetric Kits and specific acetylated at lysine 18 H3K18 and H3K36 acetylated at lysine 36 detection kits were used. Results: It was documented that total H4 histone acetylation level was increased significantly, while total H3 histone acetylation did not differ significantly. Specific histone structure and functional properties may be affected by the observed derangement of H3 histone acetylation pattern, since H3K36 site was significantly more acetylated, while H3K18 tended to be less acetylated than in control subjects. Multiple regression analysis revealed a statistically significant relationship between H4, H3T and H3K36 in BEN patients. Conclusion: This preliminary study suggests that the acetylation of histone lysine residues was detectable and found increased at specific sites of H3 and total H4 histones isolated from urothelial cells of patients with BEN. Having in mind a possible mechanism and biological role of epigenetic chromatin modification in urothelial tumor development they obtained results may open opportunity for selective therapeutic interventions in patients with BEN.     

Effect of glycemic control on microalbuminuria development among type 2 diabetes with high-normal albuminuria

This study was aimed at revealing the factors and the interrelationships between factors on microalbuminuria development among type 2 diabetes (T2D) patients. Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to-creatinine ratio (UACR) of <30?mg/g, and an estimated glomerular filtration rate (eGFR) of >60?mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical analysis had revealed that the higher baseline UACR (10?mg/g; sensitivity, 80.9%, specificity, 63.6%; AUC?=?0.774) and glycohemoglobin level (HbA1c) (8%; sensitivity, 72.1%, specificity, 61.6%; AUC?=?0.698) were the two independent microalbuminuria risk factors. When considering the risk of microalbuminuria, the data were normalized with respect to subjects with low-normal UACR (<10?mg/g) and HbA1c??8%, high-normal UACR/HbA1c?8% were 2.59 (p?=?0.107), 6.15 (p?=?0.001), and 16.96 (p?10%) showed a progressively increase of the hazard risk in baseline high-normal UACR group. But the same correlation was not shown in the low-normal UACR group. This study identified the relationships of high-normal albuminuria and glycemic control on microalbuminuria development among T2D patients. Glycemic control is especially beneficial for T2D patients with baseline high-normal UACR in preventing microalbuminuria development.     

Prognostic value of Balkan endemic nephropathy and gender on upper tract urothelial carcinoma outcomes after radical nephroureterectomy: A cohort study

BackgroundTo identify the prognostic impact of residence in a BEN-endemic area and gender on upper tract urothelial carcinoma (UTUC) outcomes in Serbian patients treated with radical nephroureterectomy (RNU).MethodsThe study included 334 consecutive patients with UTUC. Patients with permanent residence in Balkan endemic nephropathy (BEN) or non-endemic areas from their birth to the end of follow-up were included in the analysis. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates.ResultsFemale patients were more likely to have preoperative pyuria (P = 0.01), tumor multifocality was significantly associated with the female gender (P = 0.003). Gender was not associated with pathologic stage and grade, lymph node metastasis, lymphovascular invasion, adjuvant chemotherapy, bladder cancer history, tumor size, distribution of tumor location, preoperative anemia and demographic characteristics. A total of 107 cases recurred, with a median time to bladder recurrence of 24.5 months. History of bladder tumor (HR, 1.98; P = 0.005), tumor multifocality (HR, 3.80; P < 0.001) and residence in a BEN-endemic area (HR, 1.81; P = 0.01) were independently associated with bladder cancer recurrence. The 5-year bladder cancer RFS for the patients from areas of BEN was 77.8 % and for the patients from non-BEN areas was 64.7 %. The 5-year CSS for the men was 66.2% when compared to 66.6% for the women (P = 0.55).ConclusionsResidence in a BEN-endemic area represents an independent predictor of bladder cancer recurrence in patients who underwent RNU. Gender cannot be used to predict outcomes in a single-centre series of consecutive patients who were treated with RNU for UTUC.     

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.     

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.     

Albuminuria as a predictor of cardiovascular and renal outcomes in people with known atherosclerotic cardiovascular disease

BACKGROUND: Microalbuminuria predicts elevated cardiovascular risk in those with and without diabetes. In diabetes, microalbuminuria also heralds overt diabetic nephropathy. The predictive value of albuminuria below the microalbuminuria cutoff, and the development of overt nephropathy in nondiabetics with microalbuminuria, have not been well studied. We review findings of the HOPE Study. METHODS: The HOPE Study database includes data on first morning urine albumin/creatinine ratio (ACR) in 9043 participants at baseline, and in 7674 participants at baseline and at last follow-up. Inclusion criteria were known vascular disease or diabetes, plus one other cardiovascular risk factor; exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (> 1+), and serum-creatinine > 2.3 mg/dL (200 micromol/L). Microalbuminuria was defined as an ACR > or = 2 mg/mmol. RESULTS: Microalbuminuria at baseline approximately doubled the relative risk (RR) of the primary outcome (myocardial infarction, stroke, or CV death). For every 1 mg/mmol rise of ACR, even below the level of microalbuminuria, the adjusted hazard of the primary outcome increased by about 15%. Baseline microalbuminuria predicted subsequent clinical proteinuria, RR 17.5, similarly in participants without and with diabetes. New microalbuminuria developed in 1542 participants, and clinical proteinuria in 317. CONCLUSION: Albuminuria is a continuous risk factor for CV events even below the level of microalbuminuria. Microalbuminuria predicts clinical proteinuria in nondiabetics.     

Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3-year follow-up study

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n = 89), Group B (foot ulcer recurrence within 12-36 months, n = 19) and Group C (foot ulcer recurrence within 6-12 months, n = 12). The multivariate Cox regression analysis showed that urine albumin-creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005-1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032-1.096, P < .001) were identified as independent risk factors. Kaplan-Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut-off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut-off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.     

Age-related changes in cortical bone in men: metacarpal bone mass measurement study

Metacarpal cortical bone mass was measured in 507 healthy Japanese men aged 40–95 years, using a microdensitometer to determine age-related changes in cortical bone in these middle-aged and elderly men. Total bone mass showed a significant negative correlation with age (r = −0.281; P < 0.0001). While bone width showed no significant correlation with age, bone marrow width showed a significant positive correlation (r = 0.210; P < 0.0001), and cortical bone width and cortical bone density showed a significant negative correlation with age (r = −0.265; P < 0.0001; r = −0.268; P < 0.0001, respectively). On the other hand, cortical bone width and cortical bone density showed a significant positive correlation with total bone mass (r = 0.814; P < 0.0001; r = 0.474, P < 0.0001, respectively). These findings suggest that cortical bone mass decreases significantly with aging in middle-aged and elderly men, perhaps as a result of two factors — decreased cortical bone width, ie, cortical bone thinning due to bone loss at the endosteal side of the cortex, and decreased cortical bone density due to progression of intracortical porosity. Cortical bone thinning may influence age-related cortical bone loss more than decreasing cortical bone density. Received for publication on Feb. 25, 1999; accepted on July 18, 1999     

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.     

Upper urothelial tumors in emigrants from Balkan endemic nephropathy areas in Serbia

AIM: The aim of the study was to investigate upper urothelial tumors (UUT) in emigrants from Balkan endemic nephropathy (BEN) areas in Serbia and compare them with UUT from both endemic and nonendemic areas. MATERIALS AND METHODS: A total of 1,121 patients from the state cancer database, between 1960 and 1998, were investigated. Sixty of them were emigrants from BEN areas. RESULTS: UUT in emigrants from BEN areas occurred after 21.7+/-9.9 years (median 20) spent in a rural environment. The time spent outside of the BEN regions was 33.2+/-12.8 years (median 31, range 10-72). Age at surgery was 55 years (range 31-89). In emigrants from BEN areas, there was a significant association of other diseases with UUT: renal failure in 63%, bladder tumors in 23.3% and bilateralism in 6.7% of the patients. Bilateralism was statistically more frequent in emigrants from BEN areas (p=0.04), as were low-grade tumors (p=0.03). There was no statistical difference in tumor stage between patients from BEN areas and from outside of them. Relatives of the emigrants from BEN areas were also affected by BEN, UUT and both of them (33%). CONCLUSIONS: It is concluded that hereditary as well as environmental factors are important for the expression and evolution of the disease. An early period of life spent in the endemic region seems important for the later development of UUT in emigrants from BEN regions. Different time spans spent in the endemic region have no effect on the age of appearance of UUT.     

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.

     

Plasma cell infiltrates and renal allograft outcomes in indigenous and non-indigenous people of the Northern Territory of Australia

Introduction: Plasma cell‐rich rejection is a distinct histological phenomenon associated with poor renal allograft outcomes. Aboriginal and Torres Straight Islander (ATSI) transplant recipients have poorer allograft survival and higher rates of acute rejection. We sought to determine whether a higher incidence of plasma cell‐rich infiltrates (PCIR) could account for poorer survival. Methods: Renal transplant biopsies performed in recipients from the Northern Territory of Australia between 1985 and 2007 were reviewed and correlated with outcome. Biopsies were designated PCIR positive when plasma cells constituted >10% of the interstitial infiltrate. Results: Four hundred and seventy‐seven biopsies from 177 recipients (108 ATSI) were performed. Median graft survival was shorter for recipients with PCIR: 4.0 years (interquartile range 2.18–6.41) versus 5.4 years (2.0–9.99) (P = 0.013). ATSI recipients had higher rates of plasma cell‐rich rejection (RR 1.76, 95% CI 1.43–2.17, P < 0.0001), which occurred earlier (251 vs 869 days, P = 0.03) compared with non‐indigenous recipients. On multivariate analysis, PCIR did not independently influence allograft survival. There was a correlation between PCIR and panel reactive antibody peak >20% (RR 1.29, 95% CI 1.03–1.56, P = 0.025), ≥5 human leukocyte antigen mismatches (RR 1.91, 1.41–2.58, p < 0.0001), increasing post‐transplant infection rate (>10 infections RR 5.11, 1.69–15.5, P = 0.004), and subsequent death from septicaemia (RR 1.6, 1.17–2.18, P = 0.003). Conclusion: PCIR is associated with infection and markers of chronic immunological stimulation but does not independently contribute to inferior renal allograft outcomes, even in ATSI recipients.     

Accuracy of retinal changes in predicting microalbuminuria among elderly hypertensive patients: a cross-sectional study from a teaching hospital in South India

Objective  Microalbuminuria is an important marker of end organ damage in hypertensive patients, but is often not tested for, especially in a resource-poor setting. We studied the accuracy of retinal changes in predicting microalbuminuria among a cohort of geriatric hypertensive patients. Methods  One hundred and eighty elderly hypertensive patients aged more than 65 years were assessed for their demographic characteristics, smoking status, duration of hypertension, current severity of hypertension, body mass index, left ventricular hypertrophy by electrocardiogram (ECG), and high sensitivity C-reactive protein (HsCRP). Optic fundi were assessed for retinopathy after pupillary dilatation, and were photographed. Microalbuminuria (albumin–creatinine ratio) was measured as an average of two nonconsecutive overnight spot urine samples. Patients with pre-diabetes, diabetes, metabolic syndrome, treatment with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, overt nephropathy or proteinuria, and active infection were excluded. Results  Mean age was 74 ± 6.56 years. One-third were obese and 18.9% had left ventricular hypertrophy. Prevalence of microalbuminuria was 39.4% and prevalence of retinopathy was 40%. Microalbuminuria showed a strong association with retinopathy (P < 0.0001). Logistic regression identified association of microalbuminuria with duration of hypertension (P = 0.001) and elevated high sensitivity C-reactive protein (P = 0.021). Retinopathy was associated with duration of hypertension (P = 0.001) and smoking (P < 0.0001). Tests of accuracy for retinopathy as a predictor of microalbuminuria showed a sensitivity of 72% and specificity of 81%. Conclusion  Prevalence of microalbuminuria and retinopathy were quite high in our cohort of elderly hypertensive patients. Retinal changes of any grade probably have moderate accuracy in predicting microalbuminuria and hence we can initiate work-up for target organ damage, especially in a resource-poor setting.     

Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: Comparison to serum total alkaline phosphatase and serum bone Gla-protein

Summary Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35–73 years (mean 59 years) with primary hyperparathyroidism (n=7), hyperthyroidism (n=9), and hypothyroidism (n=10) in whom the bone mineralization rate (m) was determined by⁴⁷Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r=0.42,P<0.05) was found between S-T-AP and m, which in the range from 0–18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r=0.65,P<0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r=0.11,P>0.50). The highest correlation coefficient (r=0.81,P<0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r=0.71,P<0.001) than to S-T-AP (r=0.58,P<0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover. We find the assay easy to handle and suitable for large-scale use in the diagnosis and monitoring of metabolic bone disease.