Urinary Beta 2-microglobulin Levels Research Articles

Dal rene all'occhio: che cos'è la TINU?

An eight-year-old boy presenting with interstitial nephritis (abdominal pain, microhematuria, glycosuria, proteinuria, elevated urinary beta2-microglobulin levels) was eventually diagnosed with TINU syndrome (tubulointerstitial nephritis associated with uveitis) following the late onset of uveitis.

Urinary beta-2 microglobulin increases whereas TIMP-2 and IGFBP7 decline after unilateral nephrectomy in healthy kidney donors

Early kidney injury may be detected by urinary markers, such as beta-2 microglobulin (B2M), tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), kidney injury molecule-1 (KIM-1) and/or neutrophil gelatinase-associated lipocalin (NGAL). Of these biomarkers information on pathophysiology and reference ranges in both healthy and diseased populations are scarce. Differences in urinary levels of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL were compared 24 h before and after nephrectomy in 38 living kidney donors from the REnal Protection Against Ischaemia–Reperfusion in transplantation study. Linear regression was used to assess the relation between baseline biomarker concentration and kidney function 1 year after nephrectomy. Median levels of urinary creatinine and creatinine standardized B2M, TIMP-2, IGFBP7, KIM-1, NGAL, and albumin 24 h before nephrectomy in donors were 9.4 mmol/L, 14 μg/mmol, 16 pmol/mmol, 99 pmol/mmol, 63 ng/mmol, 1390 ng/mmol and 0.7 mg/mmol, with median differences 24 h after nephrectomy of − 0.9, + 1906, − 7.1, − 38.3, − 6.9, + 2378 and + 1.2, respectively. The change of donor eGFR after 12 months per SD increment at baseline of B2M, TIMP-2, IGFBP7, KIM-1 and NGAL was: − 1.1, − 2.3, − 0.7, − 1.6 and − 2.8, respectively. Urinary TIMP-2 and IGFBP7 excretion halved after nephrectomy, similar to urinary creatinine, suggesting these markers predominantly reflect glomerular filtration. B2M and NGAL excretion increased significantly, similar to albumin, indicating decreased proximal tubular reabsorption following nephrectomy. KIM-1 did not change considerably after nephrectomy. Even though none of these biomarkers showed a strong relation with long-term donor eGFR, these results provide valuable insight into the pathophysiology of these urinary biomarkers.

Comparison of Urinary Beta-2 Microglobulin Levels in Children with SSNS and Calcineurin Inhibitor-Treated SRNS.

While the utility of beta-2 microglobulin (β2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary β2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission. This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary β2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit. Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary β2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 mg/ml, P < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary β2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 mg/ml, P = 0.03). Median β2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 mg/ml). Urinary β2M levels were higher in SRNS compared to SSNS disease in remission, and β2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS.

Characterization of Urate Metabolism and Complications of Patients with Renal Hypouricemia.

Background Both renal hypouricemia (RHU) and gout are associated with renal dysfunction and urolithiasis. The difference in renal complications associated with RHU and gout, however, has not been studied. We characterized the urate metabolism and complications of patients with RHU and compared them with patients with gout. Methods Eighteen patients with RHU who had a serum uric acid (SUA) level <2 mg/dL (10 men and 8 women), 44 patients with gout (44 men) and 16 normouricemic patients (4 men and 12 women) were included. The blood and urinary biochemical data were evaluated. A genetic analysis of uric acid transporter 1 (URAT1) was also conducted in 15 cases with RHU. Results The SUA level of RHU was 0.9±0.5/mg/dl, and the Uur/Ucr and Cur/Ccr were 0.56%±0.14% and 45.7%±18.0%, respectively. A genetic analysis of URAT1 in 15 RHU patients showed that 13 harbored a URAT1 gene mutation, whereas 2 harbored the wild-type gene. The SUA level was significantly lower in RHU patients (n=11) than in either gout patients (n=44) or normouricemic patients (n=16). This reduction was accompanied by the elevation of Cua/Ccr. Urinary beta 2-microglobulin levels were higher in RHU patients than in gout or normouricemia patients. Cua/Ccr correlated with normalized urinary beta 2-microglobulin levels. The prevalence of urolithiasis was 18.2% in RHU cases and 6.8% in gout cases. A homozygous URAT1 mutation was associated with urolithiasis. Conclusion Besides urolithiasis, RHU can be associated with tubular dysfunction, such as elevated urinary beta 2-microglobulin levels.

Neurological prognostic factors for human herpes virus 6/7-associated acute encephalopathy in children: A single-center study

AimTo identify prognostic factors for severe neurological sequelae and epileptic seizures in children with human herpes virus (HHV) 6/7-associated acute encephalopathy (AE). MethodsWe retrospectively studied pediatric cases of HHV6/7-associated AE between April 2011 and March 2021. Neurological sequelae were assessed using the Pediatric Cerebral Performance Category scale (PCPC) and the presence of epileptic seizures 1 year after onset. We investigated the prognostic factors between the non-severe sequelae group (PCPC scores ≤ 2) and severe sequelae group (PCPC scores ≥ 3) in patients without severe neurological complications before onset. ResultsForty patients, ranging from 4 to 95 months old, were included. AE with biphasic seizures and late reduced diffusion were the most common types of encephalopathy (n = 28). Among the 36 patients evaluated neurological sequelae, 17, nine, eight, and two were categorized as PCPC 1, 2, 3 and 4, respectively. Epileptic seizures were observed in nine patients. In the severe sequelae group, significantly more cases with coma in the acute phase and thalamic lesions on MRI and higher serum aspartate aminotransferase, alanine aminotransferase (ALT), and lactate dehydrogenase levels were observed. Multivariate analysis showed a significant between-group difference in the rate of coma (p = 0.0405). Patients with epileptic seizures had a higher rate of coma and thalamic lesions and higher serum ALT and urinary beta 2-microglobulin levels, but there was no significant difference in the multivariate analysis. ConclusionsIn HHV6/7-associated AE, coma was a significant prognostic factor for severe neurological sequelae.

Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia.

To evaluate the role of urinary beta-2 microglobulin (B2mG) as an early predictive biomarker of acute kidney injury (AKI) in neonates with perinatal asphyxia. In this prospective cohort study, 80 term infants with perinatal asphyxia were included. The neonates were divided into AKI and no-AKI groups. Urinary B2mG levels were measured at 24h of life. The diagnostic efficacy of the biomarker was determined using receiver operating characteristic (ROC) curves. Compared to infants without AKI, infants with AKI had higher levels of urinary B2mG (mean 6.8 versus 2.6mg/L, p < 0.001). Area under the receiver operating characteristic curve (ROC curve) was 0.944. The balanced sensitivity/specificity trade-off was found at a cut-off value of 3.8mg/L (81% sensitive and 81.6% specific).Conclusion Urinary B2mG can be useful to predict AKI early in term neonates with perinatal asphyxia. What is Known: • AKI is seen in 20-40% of neonates with asphyxia. • AKI affects the treatment plan and the prognosis of such neonates. What is New: • Urinary biomarkers are the easiest way to diagnose AKI in asphyxiated neonates. • Beta 2 microglobulin is the cheapest and readily available one such urinary biomarker with good sensitivity and specificity.

Investigation of Urinary Beta-2 Microglobulin Level in Neonates with Asphyxia Admitted in Alzahra Hospitals in Isfahan, 1396-1397

Background: Despite advances in perinatal care, perinatal asphyxia (PA) remains one of the most important causes of mortality and morbidity at birth. Asphyxia is associated with the dysfunction of different organs of the body. Therefore, this study aimed to investigate the urinary biomarker of beta-2 microglobulin in neonates with asphyxia. Methods: This case-control study was performed on neonates admitted to the Neonatal Intensive Care Unit of AL Zahra and Shahid Beheshti hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran, during 2017-18. On the second day of birth, beta-2 microglobulin was measured in urine samples using the enzyme-linked immunosorbent assay technique. Results: The mean level of beta-2 microglobulin in the group with asphyxia (9.91±6.16) was significantly higher than that in the control group (3.83±4.03) (P=0.001). Moreover, analysis of beta-2 microglobulin level in the group with asphyxia showed that the mean serum level of neonates with acute renal failure (13.14±6.27) was significantly higher than that in newborns without acute renal failure (6.68±4.24) (P=0.02). Conclusion: The results of our study suggest that the beta-2 microglobulin level can be evaluated as a marker of neonatal asphyxia. Furthermore, its level was significantly associated with acute kidney injury. It is suggested that further studies be conducted with a larger sample size.

The impact of dyslipidemia on early markers of endothelial and renal dysfunction in children

BackgroundDyslipidemia has been associated with endothelial dysfunction in childhood. Impairment of renal function has been demonstrated in dyslipidemic adults. ObjectiveThe aim of this study was to assess markers of early endothelial and renal dysfunction in dyslipidemic children. MethodsThis was a cross-sectional study of 100 children with dyslipidemia and 100 age- and sex-matched control subjects without dyslipidemia aged 7–16 years. Renal dysfunction was assessed by measurement of serum creatinine and cystatin C levels, urinary beta 2-microglobulin levels, urinary albumin to creatinine (Alb:Cr) ratio, and by the estimated glomerular filtration rate (eGFR), based on serum creatinine or cystatin C. Endothelial dysfunction and early vascular changes were evaluated by ultrasound assessment of flow mediated dilation (FMD) of the brachial artery, and carotid intima-media thickness (cIMT), respectively. ResultsThe markers of early renal dysfunction showed no difference between the dyslipidemic children and control subjects except for the urinary Alb:Cr ratio that was higher in the dyslipidemic children (median, 0.007 mg/mg vs 0.005 mg/mg, p = 0.004). The urinary Alb:Cr ratio was positively correlated with the triglyceride to high-density lipoprotein cholesterol ratio (r = 0.28, p = 0.013). FMD values were lower in the dyslipidemic children than in the control subjects (8.504 ± 4.73% vs 10.535 ± 4.35%, p = 0.004), but cIMT did not differ between groups. This decrease in FMD values was evident in children aged ≥10 years. FMD was independently associated with the level of lipoprotein (a) (beta = −0.29, p = 0.01). ConclusionAmong markers of endothelial and renal dysfunction investigated, FMD was found to be lower and the urinary Alb:Cr ratio higher in children with dyslipidemia.

The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis

The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-β2M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1-1.5mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-β2M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-β2M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p < 0.001, p < 0.001, and p < 0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p < 0.001, p = 0.016, p = 0.004, microalbuminuria p < 0.001, p < 0.001, p < 0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p = 0.004). Determination of U-β2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies.

Evaluation of Renal Functions in Preterm Infants With Respiratory Distress Syndrome

The aim of this prospective study was to evaluate urinary glutathione S transferases π (GST-π), beta-2-microglobulin (B2-MG), and N-acetyl-β-d-glucosaminidase (NAG) levels as markers revealing the effect of respiratory distress syndrome (RDS) on renal function in preterm infants. The study was performed with 76 preterm infants whose gestational ages were between 28 and 32 weeks. Twenty-six preterm infants with RDS (cases) and 50 preterm infants without RDS (controls) enrolled in the study. Blood and urine samples were obtained on postnatal (PN) day 3 and 30. Urinary GST-π levels were measured by enzyme-linked immunosorbent assay (ELISA), and urinary B2-MG levels were determined by nephelometric method. There was no significant difference in urinary B2-MG and GST-π levels between RDS and non-RDS groups on PN day 3 (P > 0.05 for each). However, preterm infants with RDS had significantly higher urinary B2-MG and GST-π levels than the control group on PN day 30 (P = 0.0001 and P = 0.031, respectively). Urinary NAG levels were higher in RDS group than those of the controls on both PN day 3 and 30, but these findings were not statistically significant (P > 0.05, for each). Preterm infants with RDS had increased levels of both GST-π and B2-MG levels on PN day 30, suggesting subclinical tubular dysfunction, probably secondary to hypoxic stress.

Efficacy of N-acetylcysteine and aminophylline in preventing contrast-induced nephropathy

Contrast-induced nephropathy (CIN) is one of the important complications of coronary angiography (CAG) and percutaneous coronary intervention (PCI), especially in patients with chronic kidney disease (CKD). Prophylactic administration of N-acetylcysteine (NAC) and aminophylline has been reported to be effective in some trials, but the results still remain controversial. We investigated the efficacy of NAC or aminophylline in preventing CIN. Forty-five consecutive patients undergoing CAG and/or PCI were randomly assigned to receive hydration and NAC (704 mg orally twice daily; NAC group, n=15), hydration and aminophylline (250 mg intraveneously 30 min before CAG and/or PCI; aminophylline group, n=15), or hydration alone (control group, n=15). We compared serum creatinine (SCr), creatinine clearance (Ccr), blood beta-2 microglobulin, and urinary beta-2 microglobulin levels at baseline and 48h after CAG and/or PCI. In the NAC group, SCr decreased from 1.00 + or - 0.36 to 0.67 + or - 0.16 mg/dl (p<0.01), and Ccr significantly increased from 62.4 + or - 15.6 to 80.4 + or - 8.39 ml/min (p<0.01). In the aminophylline group, SCr and Ccr were unchanged. In the control group, SCr significantly increased from 0.94 + or - 0.21 to 1.28 + or - 0.21 mg/dl (p<0.01), and Ccr significantly decreased from 63.7 + or - 16.1 to 46.1 + or - 10.6 ml/min (p<0.01) after CAG and/or PCI. In the NAC group, mean blood beta-2 microglobulin significantly decreased from 2.38 + or - 0.58 to 1.71 + or - 0.38 mg/dl (p<0.01), and in the aminophylline group, mean urinary beta-2 microglobulin concentration significantly decreased from 337 + or - 31.0 to 239 + or - 34 microg/ml (p<0.01). These results suggest that both prophylactic NAC and aminophylline administration are effective in preventing CIN, but not with hydration alone. It appears that the two compounds work in different ways against CIN.

Urinary β 2-Microglobulin Is Associated With Acute Renal Allograft Rejection

Identifying urinary biomarkers associated with acute rejection (AR) of kidney allografts could improve recipient care by allowing AR to be diagnosed noninvasively and treated earlier. We attempted to identify novel biomarkers associated with AR by analyzing urinary proteins by using matrix-associated laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). Using MALDI-TOF MS, we analyzed urine samples from 30 renal allograft recipients with biopsy-proven AR, 15 allograft recipients without AR, preoperative samples from 29 kidney donors, and 10 subjects with proteinuric native kidney disease. In samples obtained at the time of AR, we identified a protein peak at 11.7 kd that correlated strongly with AR. In regard to its predictive power for AR, this protein peak showed sensitivity of 83.3%, specificity of 80%, positive predictive value of 89%, and negative predictive value of 70.6%, suggesting that this protein is highly associated with AR. We identified this peak as being beta2-microglobulin. This was validated by using enzyme-linked immunosorbent assay, which documented the presence of high urinary beta2-microglobulin levels in subjects with AR. Beta2-microglobulin could be a strong biomarker for AR if used in conjunction with other biomarkers, producing an AR-specific urinary protein signature. This possibility must be confirmed in a larger cohort of kidney transplant recipients.

Study of ochratoxin A as an environmental risk that causes renal injury in breast-fed Egyptian infants

Ochratoxin A (OTA) constitutes a real human threat. Its presence in human milk has previously been reported in different countries. This study is the first Egyptian report on the presence of OTA in both mothers' milk and infants' sera, addressing its correlation with infants' kidney functions, which was not previously addressed in the literature. Fifty healthy breast-lactating mothers and their infants who were exclusively breast-fed for at least 4 months were included. All of them were subjected to a thorough laboratory evaluation including determination of OTA concentration by high-performance liquid chromatography. Thirty-six mothers (72%) and their infants had been contaminated with OTA. Univariate analysis showed that the presence of OTA was associated with significantly higher levels of urinary beta2 microglobulin and microalbuminuria. Multivariate logistic regression analysis showed that there was a significant correlation between a higher OTA level in infants' sera and the degree of microalbuminuria. Mothers and their infants in our locality are exposed to a high OTA contamination rate (72%). To establish the role of OTA in causation of future renal dysfunction for infants, large controlled studies are warranted.

Proteinuria y microglobulina β2 urinaria, como marcadores de lesión tubular renal, en la valoración de la gravedad de la pancreatitis aguda

Proteinuria is a common finding in acute pancreatitis (AP). Increased urinary beta 2-microglobulin can be explained by renal tubular malfunction induced by substances released from the pancreas. The degree of renal tubular malfunction may reflect the severity of AP. To assess proteinuria and urinary beta 2-microglobulin as prognostic factors in AP. We retrospectively studied patients with AP with symptom onset within 24 hours before admission. Random urine specimens were obtained on days 1, 2 and 3 after admission. In a subgroup of 25 patients, urine samples could be obtained within 24 hours of symptom onset on day 1. The severity of AP was established using the Atlanta criteria. Proteinuria and beta 2-microglobulin were determined and were adjusted by urinary creatinine concentrations. We studied 51 patients with AP (26 men and 25 women; age: 59.6 (+/-16.7 years). Fifteen cases of AP were severe and 36 were mild. The most frequent etiology was gallstones (60.1%). Levels of proteinuria were (median and interquartile range) in mg/g creatinine: day 1: 180.5 (84.0-250.9), day 2: 164.3 (16.7-421.7), and day 3: 136.7 (24.0-371.29). Differences between severe and mild AP were significant on day 2 of admission: 339.7 (191.7-471.8) versus 120,1 (11.0-382.6); p = 0.04. Levels of urinary beta 2-microglobulin in AP on days 1 to 3 postadmission were: 9.7 (1.1-93.3), 27.6 (4.7-421.4) and 88.3 (7.3-415.2) microg/mg of creatinine, respectively. When urinary beta 2-microglobulin was compared between severe and mild AP, no significant differences were found among days 1, 2 and 3. Selection of only the subgroup of patients whose urine samples were obtained within 24 h of symptom onset, did not improve the results of these urine markers for the group as a whole. 1) Proteinuria was slightly increased in severe AP and was able to discriminate between mild and severe episodes on day 2 of admission. 2) Urinary beta 2-microglobulin as a tubular malfunction marker did not discriminate between mild and severe AP in patients in our study.

The utility of (99m)Tc-DMSA and Tc(99m)-EC scintigraphy for early diagnosis of ifosfamide induced nephrotoxicity.

A serious undesired effect of certain cytostatics is their nephrotoxicity. In this study, we investigated the toxic effects of ifosfamide and cisplatin by clinical and biochemical parameters in relation to (99m)Tc-dimercaptosuccinic acid ((99m)Tc-DMSA) and Tc(99m)N, N-ethylenedicysteine (EC) renal scintigraphy. The indicators were urinary beta2-microglobulin levels, tubular resorption of phosphate, urinary protein and glucose excretion, glomerular filtration rate, urinary pH and osmolarity. Thirteen paediatric patients (seven boys and six girls), aged 2-16 years, were investigated. Five patients received only cisplatin, six patients were treated with ifosfamide and cisplatin and two with ifosfamide and carboplatin for various malignancies. All except three patients had normal DMSA uptake (median, 19; range, 16-29%) prior to chemotherapy. The reduction in DMSA uptake was unilateral due to tumour invasion in those three patients. Following chemotherapy, DMSA uptake showed reduction in five patients with or without clinical nephrotoxicity. The observed pattern was decreased renal uptake and elevated bladder activity. Three patients with decreased DMSA uptake had normal tubular maximum phosphate reabsorption, which suggested subclinical injury. Decrease in DMSA uptake and tubular phosphate reabsorption (TPR) was detected simultaneously in two patients. No abnormalities were seen on Tc(99m)-EC scintigraphy to suggest nephrotoxicity in our investigation. However, Tc(99m)-EC clearly demonstrated a reduction in split renal function in children with tumour invasion. In summary, we found that ifosfamide induced tubular injury can be detected with (99m)Tc-DMSA scintigraphy before chemotherapy associated nephrotoxicity is observed by laboratory measurements. Our results also imply that, although a tubular agent, renal scintigraphy performed with Tc(99m)-EC is not able to detect subclinical injury or predict the outcome during treatment.

Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome.

We describe a prospective study of 2-year moderate-dose cyclosporin (CS) treatment in 13 children with steroid-dependent minimal change nephrotic syndrome (MCNS). CS treatment was commenced at 100-150 mg/m2 per day after remission was attained with prednisolone therapy, was adjusted to a target trough level of 100 ng/ml, and was administered for 2 years. The number of relapses during CS treatment significantly decreased compared with before CS treatment, all patients were able to discontinue prednisolone therapy, and steroid toxicity was reduced; 54% of patients remained in remission during CS treatment. Renal biopsies performed before CS treatment all showed MCNS without tubulointerstitial lesions. Creatinine clearance and urinary beta 2-microglobulin levels during CS treatment were normal in all patients, but renal biopsies performed after CS treatment revealed chronic CS nephrotoxicity in 7 patients. Clinical data, including CS dose and CS trough blood levels, were not significantly different between patients with and without nephrotoxicity. In conclusion, 2-year moderate-dose CS treatment in children with steroid-dependent MCNS is effective in preventing relapse and decreasing steroid toxicity. This treatment can, however, result in a high incidence of chronic nephrotoxicity. Renal function is not a reliable indicator of chronic CS nephrotoxicity. Renal biopsy is therefore necessary to monitor chronic CS nephrotoxicity.

Followup Study of Renal Function in Children With Reflux Nephropathy After Resolution of Vesicoureteral Reflux

We evaluated data collected for 10 years on children with reflux nephropathy to identify a means of predicting the prognosis. A total of 15 boys and 13 girls were enrolled in this study at least 2 years after surgical and spontaneous resolution of vesicoureteral reflux in 25 and 3 patients, respectively. They were followed for more than 10 years and renal function was periodically evaluated. Urinary beta 2-microglobulin, alpha 1-microglobulin, N-acetyl-beta-D-glucosaminidase, microalbumin and 99mtechnetium dimercapto-succinic acid uptake were measured. Of the 28 patients 12 had high levels of urinary alpha 1-microglobulin during followup, including all 7 in whom renal function deteriorated. In 3 children with elevated alpha 1-microglobulin urinary microalbumin gradually increased after puberty. Although elevated levels of urinary beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase and microalbumin were also observed, they were less predictive of renal function than alpha 1-microglobulin. These results suggest that elevated urinary levels of alpha 1-microglobulin may predict the risk of abnormal renal function in children with reflux nephropathy even before the appearance of significant proteinuria.

Protective Effects of Nifedipine and Allopurinol on High Energy Shock Wave Induced Acute Changes of Renal Function

In a prospective randomized study, the effects of a calcium antagonist (nifedipine) and a xanthine oxidase inhibitor (allopurinal) on high energy shock wave induced impairment of renal function were examined. A total of 40 patients with renal pelvis or caliceal stones undergoing anesthesia-free extracorporeal shock wave lithotripsy (ESWL) without auxiliary measures was randomly assigned to 4 groups. Group 1 received no medication and the others received nifedipine (group 2), allopurinol (group 3) or nifedipine plus allopurinol (group 4), respectively. Nifedipine (20 mg. each) or allopurinol (0.2 gm. each) was given orally 3 times a day for a total of 4 days beginning the night before ESWL. To assess renal function the urinary excretions of beta 2-microglobulin, albumin and Tamm-Horsfall protein were determined by radioimmunoassay. After ESWL there was a significant increase in urinary beta 2-microglobulin and albumin (p < 0.001), and the urinary Tamm-Horsfall protein decreased significantly (p < 0.01) compared with before ESWL in group 1. In groups 2 and 4, however, all of the parameters after ESWL were not significantly different compared with the values before ESWL. Although the levels of urinary beta 2-microglobulin and albumin after ESWL were significantly higher (p < 0.05) than the pre-ESWL levels in group 3, the changes in urinary albumin and Tamm-Horsfall protein were milder in group 3 than in group 1. In addition, the urinary albumin level in group 2 and the urinary beta 2-microglobulin or albumin level in group 4 were less significantly different (p < 0.05) than the levels in group 1. All parameters before ESWL were not significantly different among the groups. Our results indicated that nifedipine and/or allopurinol exhibits a protective effect on high energy shock wave induced renal damage.

Urinary Trehalase Activity in Chronic Glomerulonephritis

To determine the diagnostic role of urinary trehalase in chronic glomerular disease, urinary trehalase activity and other urinary markers such as N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (gamma-GTP), lactate dehydrogenase (LDH), lysozyme and beta 2-microglobulin (BMG) were measured in patients with chronic glomerulonephritis, nephrotic syndrome and chronic renal failure. Urinary trehalase activity was significantly increased in chronic glomerular disease, especially nephrotic syndrome, as compared with that in the healthy subjects. The highest incidence of elevated excretion was observed for trehalase with 52% in chronic glomerular disease, followed by NAG. Urinary trehalase activities in the patients were significantly correlated with the urinary levels of protein, NAG and AAP and total score of tubular damage, but not correlated with urinary levels of BMG or lysozyme. In patients with chronic glomerulonephritis and nephrotic syndrome, there was no significant difference in urinary trehalase activities between with and without hematuria. These results indicate that in some patients with chronic glomerular disease, there is tubular involvement as substantiated by elevation of the other urinary enzymes and BMG. Urinary trehalase is elevated more often in these types of disease than other markers of tubular damage.

Frequency of elevated urinary ?2 levels in relatives of patients with asymptomatic low-molecular-weight proteinuria

We studied urinary beta 2-microglobulin levels in a total of 29 apparently healthy relatives (aged 0.8-70 years) of 8 male patients with asymptomatic low-molecular-weight proteinuria in six families. The frequency of levels above the age- and sex-associated 95% confidence limit was 7 of 29 (24%), 4 of 12 (33%) in first-degree relatives, 2 of 6 (33%) fathers, and 2 of 6 (33%) mothers. These frequencies were significantly above those in the general population (P less than 0.01, by a normal distribution test, a binomial distribution, and Poisson distribution test for the sample proportion). The increased frequency in fathers argues against an X-linked pattern of inheritance for this entity, suggesting that there is heterogeneity in the inheritance.