Urinary albumin excretion in Spanish children

We measured urinary albumin excretion in 2,224 school-children (1,168 boys, 1,056 girls) aged 2–18 years, between 1989 and 1990 to establish reference values. We recorded all pathological antecedents and findings from physical examination, including anthropometric parameters and arterial blood pressure. The analytical study included serum total protein, albumin and creatinine. The second-morning urine and the nightly (rest) 10-h urine sample were collected and we determined the concentration of albumin and creatinine. We found a positive statistically significant correlation between the urinary albumin excretion (g/10 h) and age, height, weight and body surface area. We suggest that it would be useful to relate the urinary albumin excretion to body surface area. The mean value for albumin excretion was 3.49 g/ml in boys and 3.63 g/ml in girls. The urinary albumin/creatinine ratio showed a high correlation with the albumin excretion (r=0.958).The following members are co-authors of this report: N. Caballo, M. A. Arias, C. Serna, M. Ramirez and A. Cornejo     

Urinary calcium and oxalate excretion in children

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1–7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean±SD=0.39±0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34±0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61–280) mol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6–82) mol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28–49) vs. 22 (range 16–29) and 23 (range 22–27) mol/mol respectively,P<0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18±0.05 vs. 1.06±0.03,P<0.03 and 0.84±0.03,P<0.001 respectively). The measurement of Ca/Cr and Ox/Cr in first-morning urine samples is suitable for screening for hypercalciuria and hyperoxaluria. Interpretation of the values requires age-specific reference values. Both calcium and oxalate determinations should be part of the evaluation of patients with haematuria, hypercalciuria or nephrolithiasis.     

Differential excretion of urinary proteins in children with vesicoureteric reflux and reflux nephropathy

We studied 40 children with a history of vesicoureteric reflux (VUR) without evidence of renal scarring, 93 children with a history of VUR and renal scarring and 10 children with previous urinary tract infections in whom the urinary tract was radiologically normal. Urine retinol-binding protein (RBP), albumin andN-acetyl--d-glucosaminidase (NAG) were measured in each child. All were free from infection at the time of the analysis. Urinary RBP and NAG levels were significantly elevated (P<0.001) in the group of children with renal scarring. Elevated RBP levels were detected in 51% of children with bilateral renal scarring compared with 7% of children with unilateral scarring. Urine RBP excretion increased progressively according to the type of scarring, best determined by the type of scarring of the less affected kidney. In children with renal scarring, elevated NAG levels were seen mostly in the 65 children with bilateral scarring and severe reflux. Urine albumin excretion was elevated in 10 children, 9 with bilateral scarring, all of whom had elevated RBP excretion. Urine protein excretion was unaffected by the presence or absence of persisting VUR. There was a strong negative correlation between glomerular filtration rate and RBP excretion (r=–0.69). We conclude that evidence of tubular dysfunction is common in children with bilateral renal scarring and usually precedes any glomerular protein leak. Tubular dysfunction may be the consequence of relative nephron hyperperfusion in the presence of bilateral scarring.     

Variability of urine albumin excretion in normal and diabetic children

The variability of urine albumin excretion (UAE) was studied in normal and diabetic children and, in addition, the best method of expressing the data was investigated. In 39 timed overnight urine samples from diabetic children, the urine albumin creatinine clearance ratio (CA/CC) was compared with the urine albumin creatinine concentration ratio (UA/UC), the urine albumin excretion rate (UAER) and the urine albumin concentration (UA). UA/UC predicted CA/CC (r=0.95) better than either UAER (r=0.83,P<0.02) or UA (r=0.90), 0.1>P>0.05). The within-individual and the between-individual variability in overnight UA/UC in 171 urine samples from 73 normal children was compared with that of 406 urine samples from 119 diabetic children, using a random effects type 2 nested analysis of variance model. Geometric mean (range) UA/UC (mg/mmol) in diabetic children, 0.55 (0.04–6.90), was greater than in normal children, 0.33 (0.05–2.10,P<0.01), and 18% of diabetics had a value of UA/UC above the normal range. Within-individual variance was the same in normals (0.12) and diabetics (0.12), but between-individual variance in diabetics (0.18) was much greater than in normals (0.03). These data show that within-individual observations for both normals and diabetics are highly but equally variable. Furthermore, from these data, it is possible to infer that a minimum of five estimations are necessary per individual to estimate the true mean value of urine albumin excretion with reasonable confidence.     

Long-term follow-up after unilateral nephrectomy and radiotherapy for Wilms' tumour

Twenty-nine patients who had had unilateral nephrectomy for Wilms' tumour in one hospital were known to have survived more than 12 years. Sixteen agreed to attend for clinical review, of whom 14 had estimation of serum creatinine, 24-h urine protein excretion and endogenous creatinine clearance. The follow-up period was 13–26 years (median 17 years). All but one had had radiotherapy and all had chemotherapy (actinomycin D, 16; vincristine, 5). Some degree of kyphoscoliosis was present in all except the patient who did not receive radiotherapy. Four patients had diastolic blood pressure 90 mmHg or greater. Two patients had mild proteinuria (392, 361 mg/day). Serum creatinine ranged from 53 to 125 mol/l and endogenous creatinine clearance ranged from 39 to 173 ml/min (median 81, mean 89). Of the 7 patients who were 20–26 years postnephrectomy, 2 were hypertensive and 1 had elevated urinary protein excretion. We conclude that the long-term prognosis of unilateral nephrectomy in childhood is good.     

Diagnostic value of urinary retinol-binding protein in childhood nephrotic syndrome

Urinary excretion of N-acetyl-β-d-glucosaminidase (NAG) and retinol-binding protein (RBP), sensitive markers of renal tubular damage and dysfunction respectively, were evaluated in paired remission and relapse urine samples from 16 patients (median age 12 years), with minimal change nephrotic syndrome (MCNS), in single samples from 5 nephrotic patients (median age 12 years) with focal segmental glomerulosclerosis (FSGS) and in 183 normal controls aged 2–16 years. The NAG and RBP data were expressed as a ratio over urinary creatinine (Cr). The NAG/Cr and RBP/Cr geometric means (ranges) for normal subjects were 11.1 (3.4–35.5) μmol 2-methoxy-4-(2"-nitrovinyl)-phenol (MNP)/h per mmol and 3.1 (0.3–38.8) μg/mmol, respectively. The NAG/Cr data revealed a weak negative correlation with age in normal children, whereas RBP/Cr was independent of age. RBP/Cr and NAG/Cr in MCNS in remission were the same as in controls. In MCNS in relapse, NAG/Cr was significantly elevated (P=<0.001), while in FSGS both RBP/Cr and NAG/Cr were significantly raised (P=<0.001 and P<0.008, respectively). These findings suggest that elevated NAG/Cr may be an indicator of relapse in both MCNS and FSGS and elevated RBP/Cr may allow differentiation between the two. Received May 7, 1997; received in revised form January 30, 1998; accepted February 4, 1998     

Pathophysiology of the renal acidification defect present in the syndrome of familial hypomagnesaemia-hypercalciuria

A distal acidification defect is frequently observed in the syndrome of familial hypomagnesaemia-hypercalciuria and hence this condition can be confused with prirnary distal renal tubular acidosis (RTA). This study demonstrates that in four unrelated patients with familial hypomagnesaemia-hypercalciuria the acidification defect is functionally different from that present in primary distal RTA. All patients exhibited hypomagnesaemia, hypermagnesuria, hypercalciuria, hyposthenuria, nephrocalcinosis and slight reduction of glomerular filtration rate (GFR). A moderate degree of metabolic acidosis was also present and basal data showed an inappropriately high urine pH (5.7–5.9) and a positive urine anion gap (Na+KCl=11–28 mmol/l). Stimulation of distal acidification induced a fall in urine pH (4.7–5.6), but ammonium excretion remained low despite factoring by GFR (26–46 mol/min per 1.73 m², 35–54 mol/100 ml GF). The urine to bloodPCO₂ gradient also remained low after sodium bicarbonate loading (1.3–17.7 mmHg). These results are best explained by both defective ammonia transfer to the deep nephron and impaired hydrogen ion secretion at the level of the medullary collecting duct, and probably are secondary effects of the medullary interstitial nephropathy.     

Serum hippuric acid concentration in renal allograft rejection,ureter obstruction,and tubular necrosis

Plasma from 35 renal allograft recipients (21 males and 14 females) was sampled daily and analyzed for hippuric acid (HA) by highperformance liquid chromatography (HPLC) and serum creatinine. Twelve of these patients experienced an acute renal allograft rejection or a ureter obstruction as proven by clinical signs and biopsy, as well as by radiography or ultrasound, respectively. Two patients suffered from tubular necrosis followed by rejection during the postoperative period. Mean serum HA increased by 39.9 mol/l from baseline (range 20.4–115.5 mol/l) in patients with acute rejection 3 days after an initial increase that was observed 24 h before the mean serum creatinine increased by 107.1 mol/l (range 21–193 mol/l). In cases of ureter obstruction, HA rose by 1.6 mol/l (range 1–8.2 mol/l), significantly less than elevations due to rejection. The increase in creatinine, however, amounted to 65.3 mol/l (range 22–140 mol/l) and was not different from the change in rejecting patients. Successful antirejection treatment coincided with a decrease in serum HA starting 24 h earlier than the decrease in the serum creatinine concentration. Of special interest was the observation of a parallel decrease in HA with creatinine concentration in patients with tubular necrosis after allotransplantation; HA increased in cases of an additional rejection. Our data suggest that HA, which is excreted by tubular secretion and glomerular filtration, could be a sensitive and early marker of acute allograft rejection. Furthermore, it seems to discriminate between acute renal allograft rejection and ureter obstruction. It might, therefore, be of value in the diagnosis of rejection complicating tubular necrosis after transplantation.     

Urinary excretion of brush border antigens and other proteins in children with vesico-ureteric reflux

This study was designed to evaluate the occurrence and the type of proteinuria in 82 children with vesico-ureteric reflux (VUR) with or without renal scars. The urinary excretion of the high molecular weight protein albumin was taken as an index of glomerular alterations and the excretion of retinol-binding protein (RBP), ₂-microglobulin and brush border antigens (BBA) (measured by monoclonal antibody-based enzyme-linked immunosorbent assay) was taken as an index of tubular alterations. All such markers were increased in children with VUR and were related to the degree of renal function. Patients showing reduced creatinine clearance had very high levels of albuminuria, microproteinuria and BBA, with all these varialbles reciprocally correlated. In children with normal renal function however, only microproteins (not albumin or BBA) were slightly increased, thus indicating an isolated tubular defect without involvement of the proximal segment of the tubule. However, microprotein excretion did not correlate with the grade of scarring (^99mtechnetiumdimercaptosuccinic acid scan), both RBP and ₂-microglobulin excretion being normal in 75% of children with radioisotopic signs of renal lesions but increased in 17% of children without scars. Therefore, tubular proteinuria identifies different groups of children with VUR but is not related to renal scarring. Prospective studies will define the usefulness of proteinuria as a reliable indicator of renal outcome.     

Urinary excretion of retinol-binding protein in healthy children and adolescents

Retinol-binding protein (RBP) is a marker of tubular reabsorption in the kidneys. The aim of our study was to investigate urinary RBP excretion in healthy children to obtain reference values related to age and pubertal stage. Overnight samples from 143 subjects (73 girls, 70 boys) aged 10–18 years were investigated. RBP was quantified by a solid-phase sandwich enzyme immunoassay. Both the RBP excretion rate and the RBP/ creatinine ratio (RBP/Cr) showed a skewed distribution. The medians and the 5th–95th percentiles were 38 ng/min (15–127) and 9 μg/mmol (4–23), respectively. The RBP excretion rate and RBP/Cr ratio were similar in both sexes, and linear multiple regression analysis showed no association with age or pubertal stage, although a weak relationship (r = 0.27) was found between RBP excretion rate and age in boys and RBP/Cr ratio and age (r = -0.28) in girls by simple correlation analysis. The correlation between RBP excretion rate and RBP/Cr ratio was 0.76; the RBP excretion rate and RBP/Cr ratio measured on 2 consecutive days, showed a correlation coefficient of 0.84 and 0.88, respectively. We conclude that overnight RBP excretion in children over 10 years shows a low day-to-day variation and, in practical terms, is independent of age, gender and pubertal stage.     

Functional parameters and99mtechnetium-dimercaptosuccinic acid scan in acute pyelonephritis

The diagnostic value of^99mtechnetium-dimercaptosuccinic acid (DMSA) scintigraphy, ultrasonography and renal functional parameters [urineN-acetyl--d-glucosaminidase (NAG)/creatinine and urine albumin/creatinine quotients] in acute pyelonephritis (APN) were studied in 39 children (28 girls, 11 boys, median age 9 months, range 2 weeks to 9.4 years, 28 patients <1 year, 11 patients >1 year) with first-time urinary tract infection. Ultrasonography of the urinary tract was performed on admission and together with DMSA scintigraphy (<10 days from admission). Urine NAG/creatinine and urine albumin/creatinine quotients were measured daily and after 6–8 weeks. Ultrasonography revealed abnormalities in 12 of 39 (31%) patients [11/32 patients (34%) with positive DMSA scintigraphy], while DMSA uptake defects were present in 32 of 39 (82%) patients [21/28<1 year (75%), 11/11 >1 year (100%),P=0.08]. Urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in children <1 year with APN, as well as in non-renal fever controls, than in older children. However, in both age groups the urine NAG/creatinine and urine albumin/creatinine quotients were significantly higher in APN than in non-renal fever. The urine NAG and albumin excretion decreased rapidly after the initiation of antimicrobial therapy and had normalized at 6–8 weeks. The size and grade of the DMSA uptake defect (DMSA score) did not correlate with duration of disease at admission, maximum C-reactive protein or maximum fever. The urine NAG/creatinine quotient in the children <1 year showed, however, a significant correlation with the DMSA score (r=0.58,P<0.05), while no correlation was found in the older children. We conclude that DMSA scintigraphy is a sensitive method to confirm the clinical diagnosis of APN, although a substantial number of infants appear to have normal scans. Early determination of the urine NAG/creatinine and albumin/creatinine quotients may further improve the diagnostics in the infant.     

Microproteinuria in children with vesicoureteric reflux

Microproteinuria was assessed by the measurement of albumin, retinol binding protein (RBP) and creatinine concentrations in random midstream urine samples using a single enzyme linked immunoassay (ELISA) in 36 children with vesicoureteric reflux (VUR) and 36 control patients. Infection was excluded by culture and microscopy of the specimens of urine. No patient was hypertensive. Albumin excretion increased in patients with increasing severity of VUR and with renal scarring. Similar findings were observed with RBP excretion. The results show that glomerular and tubular handling of proteins is altered in VUR. The degree of microproteinuria correlates well with the severity of the VUR and is evidence of tubular dysfunction. The effects of medical management and anti-reflux surgery on microproteinuria require further evaluation.     

Increased urinary albumin indicating urothelial leakage following intravesical bacillus Calmette-Guérin therapy for superficial bladder cancer

Summary This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL) 1, IL2, IL6, and tumor necrosis factor alpha (TNF) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2–432) g albumin/ml urine, approximating 14±14 g/ mol creatinine (creat) (n=15), which was comparable to the mean pre-instillation value of 16±32 g/mol creat (n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed (P<0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3–6. A significant correlation between albumin and concentration of the cytokines IL1, IL2, IL6, and TNF was found (P<0.01), correlation coefficients (r) being 0.56, 0.56, 0.67, and 0.71 (n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFIL2albuminIL6IL1. TNF peaked most frequently after 2–4h and IL1 after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a leakiness of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy.     

Renal function in Laron syndrome patients treated by insulin-like growth factor-I

Eight children with Laron syndrome (5 males, 3 females) aged 3–14.5 years received daily subcutaneous injections of 150 g/kg recombinant insulin-like growth factor-I (IGF-I) for 5 months. The children were examined weekly for the 1st month and then once monthly. At each visit, overnight fasting blood was drawn for serum IGF-I and blood chemistry measurements and a 24-h urine collection was performed for the determination of calcium, phosphorus, creatinine and nitrogen. The main effects related to kidney function were: an initial weight gain with a mild transitory reduction in the urinary volume, an increase in serum electrolyte concentrations and a decrease in urinary electrolyte excretion. The lower than normal mean (± SEM) basal creatinine clearance (76.7±15.8 ml/min per 1.73 m²) increased towards the normal range during treatment to 124.9±13 ml/min per 1.73 m², with a mean increment of 73.4±28% (P<0.02) from basal values after 2 months of treatment, without changes in the serum creatinine. Initially an increase in blood urea nitrogen was observed together with a reduction in urinary nitrogen excretion. During the IGF-I therapy the urinary calcium excretion increased from 0.7±0.2 nmol/day to 1.5±0.3 nmol/day and the tubular reabsorption of phosphate increased from 1.24±0.06 to more than 1.38±0.04 nmol/l (P<0.002), resulting in a significant increase in serum phosphate levels from 1.51±0.06 to more than 1.63±0.04 nmol/l (P<0.005). The present study shows for the first time that long-term IGF-I deficiency in man results in a subnormal glomerular filtration rate and that chronic substitution therapy with IGF-I has marked renotropic effects identical to those ascribed to growth hormone.     

Tubular proteinuria defined by a study of Dent's (CLCN5 mutation) and other tubular diseases

Tubular proteinuria defined by a study of Dent's ( CLCN5 mutation) and other tubular diseases. BACKGROUND: The term "tubular proteinuria" is often used interchangeably with "low molecular weight proteinuria" (LMWP), although the former implies a definite etiology. A specific quantitative definition of tubular proteinuria is needed, and we address this by studying five different renal disorders. METHODS: Tubular proteinuria was assessed by measuring urinary retinol-binding protein (RBP), beta2-microglobulin (beta2M), alpha1-microglobulin (alpha1M), and albumin in 138 patients: 26 affected males and 24 female carriers of the X-linked syndrome "Dent's disease," 6 patients with other Fanconi syndromes, 17 with distal renal tubular acidosis (dRTA), 39 with glomerulonephritis (GN), and 26 with Chinese herbs nephropathy (CHN). RESULTS: RBP was better than beta2M or alpha1M in identifying the tubular proteinuria of Dent's disease. Median urinary RBP levels in mg/mmol creatinine were: affected male Dent's, 18.2, N = 26; carrier female Dent's, 0. 30, N = 24; dRTA, 0.027, N = 17; GN, 0.077, N = 39; and normal adults, 0.0079, N = 61. Elevated urinary RBP (>0.017) and albumin < (10 x RBP) + 2 identified all patients with the LMWP of Dent's disease and clearly distinguished their LMWP from that of dRTA and GN. This is a quantitative definition of tubular proteinuria. Consistent with this definition, 80% of those patients with CHN who had an elevated RBP had tubular proteinuria. Urinary RBP and albumin in carriers of Dent's disease were strikingly correlated over a 100-fold range (R = 0.933). CONCLUSION: The combination of elevated urinary RBP (>0.017) and albumin < (10 x RBP) + 2 (mg protein/mmol creatinine) is a quantitative definition of tubular proteinuria. Furthermore, our findings suggest that a shared defect in tubular RBP and albumin reuptake causes this form of proteinuria.     

Low molecular weight protein excretion in glomerular disease: a comparative analysis

We studied 23 children with steroid-sensitive nephrotic syndrome (SSNS), 21 children with steroid-resistant types of nephrotic syndrome and 32 children with other types of nephritis. Our controls were 43 apparently healthy children. We measured the urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) and the low molecular weight (LMW) proteins β₂-microglobulin (B2M), retinol-binding protein (RBP), α₁-microglobulin (A1M) and urine protein 1 (UP1). Results for B2M were considered only for a urine pH greater than 6.0. Comparisons were made with urine albumin excretion, glomerular filtration rate (GFR) and tubular abnormalities in selected renal biopsy samples. We found that abnormalities of LMW protein excretion occurred in between 50% (B2M) and 88% (UP1) of all subjects. In children with SSNS, A1M (r = 0.73), UP1 (r = 0.65) and NAG (r = 0.54) excretion were significantly correlated with albumin excretion, but not RBP or B2M excretion. Increased fractional excretion of A1M, B2M and UP1 and increased plasma A1M were demonstrated in 9 children with SSNS, suggesting competition for tubular reabsorption with albumin, most marked for UP1. In the steroid-resistant nephrotic and nephritic syndromes, correlation with albumin was found for all proteins. In these subjects, RBP (r = 0.37), B2M (r = 0.42) and A1M (r = 0.28) were inversely correlated with GFR, but not UP1, NAG or albumin. We found that RBP excretion was significantly greater in the presence of severe tubular abnormalities in 11 children with recent renal biopsies, but not A1M, UP1 or NAG. We conclude that LMW proteinuria is common in children with glomerular disease, and does not necessarily imply a poor prognosis. Factors other than histologically proven tubular abnormality may account for elevated LMW protein excretion. RBP is the LMW protein most closely associated with structural abnormality and least affected by increasing albuminuria. Received January 31, 1996; received in revised form and accepted October 22, 1996     

Acidosis prevents growth hormone-induced growth in experimental uremia

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65–71 mol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 mol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in nonacidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.     

Pore size and charge selectivity of the glomerular membrane at the time of diagnosis of diabetes

The urinary albumin excretion rate is increased at the time of diagnosis of diabetes. We investigated whether this is caused by change in pore size or charge selectivity in the glomerular basement membrane. Urine excretion of immunoglobulins (IgG2, IgG4), glycosaminoglycans (GAG), and albumin was analyzed during the first 20 days after diagnosis of diabetes in children aged 4–15 years; 36 diabetic and 24 age-matched apparently healthy children were included. The excretion of albumin was significantly increased on day 1 in the diabetic children. Between day 1 and 20 the excretion of IgG2 and IgG4 decreased significantly from normal to a level below normal. GAG excretion was not affected. The GAG/creatinine index (GAGCI) was normal. IgG2CI was significantly below normal on days 4–20. IgG4CI was below normal on days 2–20. The albumin creatinine index decreased significantly from day 1 to normal levels on day 4–20. A charge selectivity index, expressed as the ratio between the neutrally charged IgG2 and the negatively charged IgG4, was significantly below the normal level on days 16 and 20. In conclusion, an increased albumin excretion rate in urine did not seem to be caused by a change in charge selectivity. Other explanations such as change in the small pore radius or tubular reabsorption are suggested.     

Low molecular weight proteins in children with renal disease

Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include ₂-microglobulin (B2M), retinolbinding protein (RBP), ₁-microgloulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.     

Urinary thromboxane B2 as an indicator of acute rejection in human liver transplantation

Urinary thromboxane B₂ (u-TXB₂) was measured and analyzed after a human liver transplantation in 28 patients (30 transplantations) who underwent an orthotopic liver transplantation. Our results showed that the u-TXB₂ levels exceeded 3.0g/mmol creatinine in only 2 of the 13 cases that had a favorable postoperative course. In 10 of the 11 episodes of acute rejection, the u-TXB₂ levels exceeded 3.0g/mmol creatinine. In 6 episodes of acute rejection, the TXB₂ levels were more than 5.0. In 4 out of 6 episodes of infection unassociated with rejection, the u-TXB₂ values were between 3.0 and 4.9g/mmol creatinine. In 2 episodes of liver necrosis the TXB₂ value reached 5.3 in one and 0.9 in the other. In conclusion, the u-TXB₂ level was observed to be elevated in cases of acute rejection, infection, or necrosis. The diagnosis of acute rejection on the basis of u-TXB₂ showed a sensitivity of 58.8%, a specificity of 93.3%, and an accuracy of 75.0% for a threshold level of 3.0g/mmol creatinine, and a sensitivity of 85.7%, a specificity of 79.2%, and an accuracy of 80.6% for a threshold level of TXB₂ of 5.0g/mmol creatinine. These results indicate that the serial determination of u-TXB₂ is a useful diagnostic means for predicting acute rejection after liver transplantation.