Renal glucosuria in schoolchildren: Clinical characteristics.

BACKGROUND: We conducted an annual urine glucose screening program at schools, and diagnosed schoolchildren with diabetes at an early stage of the disease. We also identified some cases of renal glucosuria (RG), based on positive urine glucose with normal glucose tolerance. METHODS: During 2000-2015, 3 309 631 schoolchildren participated in the screening program. The positive rate for glucosuria in the first test was approximately 0.1%, whereas on repeat urine test it was approximately 0.05%. In total 350 schoolchildren were positive for glucosuria on detailed examination. Oral glucose tolerance test (OGTT) was also used to evaluate glucose intolerance. RESULTS: One hundred and two schoolchildren (29.7%) were diagnosed with diabetes, whereas RG was identified in 246 (70.3%) with normal glucose metabolism. In regard to the characteristics of RG, the percentage of boys was 50.3%, and the mean age at diagnosis was 11.2 ± 2.4 years. Twenty-eight children (11.4%) were overweight (body mass index standard deviation score [BMI-SDS] > +2.0 SD), whereas five (2.0%) were underweight (BMI-SDS < -2.0 SD). First-degree family history was suspected in 176 cases (71.5%). All RG subjects had normal glucose tolerance in the absence of insulin resistance and decreased insulin secretion (homeostasis model assessment for ß-cell function, 78.8 ± 59.5%) on OGTT. CONCLUSIONS: RG is not rare in Japanese schoolchildren with glucosuria. This disorder seems to have a strong genetic background, and to involve less growth retardation and weight loss than expected despite continuous excretion of glucose in urine.

Persistently high urine glucose levels caused by familial renal glycosuria.

Glycosuria generally occurs when the threshold for glucose reabsorption by the proximal renal tubule is exceeded or when reabsorption of filtered glucose is impaired. Although the discovery of glycosuria in a child will prompt screening for diabetes mellitus, it is also a sign of a rare tubulopathy called "familial renal glycosuria" (OMIM #233100). This tubulopathy is linked to a defect in the sodium-glucose co-transporter 2, encoded by the SLC5A2 gene. Here, we describe and discuss two pediatric cases in whom familial renal glycosuria was discovered fortuitously after the observation of persistently high urine glucose levels in the absence of hyperglycemia.

Transient renal tubulopathy in a racing Greyhound.

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Identification of a novel form of renal glucosuria with overexcretion of arginine, carnosine, and taurine.

Glucosuria occurs in diabetes mellitus, generalized proximal tubular dysfunction of Fanconi's syndrome, glucose-galactose malabsorption syndrome, and primary renal glucosuria. Patients with primary renal glucosuria have normal blood glucose levels, normal oral glucose tolerance test results, and persistent glucosuria that may approach the filtered load of glucose in the most severe cases. The primary defect is proposed to be in the sodium-glucose cotransporter type-2 (SGLT2) located in the apical membrane of S1 segment proximal renal tubule cells. Primary renal glucosuria is classified as types A, B, or O based on the characteristics of the transport defect. The magnitude of glucosuria has varied from 20 to 150 g of glucose excreted in 24 hours. Described inheritance patterns have included both autosomal dominant and autosomal recessive mechanisms. Some cases have been associated with selective aminoaciduria, distinctly unlike the generalized aminoaciduria seen in Fanconi's syndrome. We report the first case of primary renal glucosuria with selective overexcretion of arginine, carnosine, and taurine. This case may represent a genetic defect unique from the abnormalities in previously described cases of primary renal glucosuria with different amino acid excretion patterns. Future investigations could determine whether the syndrome involves a defect in the SGLT2 gene.

Familial renal glycosuria and modifications of glucose renal excretion.

Under physiological conditions, the kidneys contribute to glucose homoeostasis by producing glucose by gluconeogenesis and preventing glucose loss in urine. The glucose filtered by the glomeruli is completely reabsorbed in the renal proximal tubule. Renal gluconeogenesis produces 25% of the circulating glucose in the postabsorptive state, while the amount of glucose reabsorbed by the kidneys largely exceeds the quantity synthesized by kidney gluconeogenesis. Sodium-glucose cotransporter type 2 (SGLT-2) and glucose transporter 2 (GLUT2) carry out more than 90% of renal glucose uptake. In diabetes, both gluconeogenesis and renal glucose reabsorption are increased. The augmentation of glucose uptake in diabetes is due to the overexpression of renal glucose transporters SGLT-2 and GLUT2 in response to the increase in expression of transcription activator hepatic nuclear factor 1-alpha (HNF1α). The rise in glucose uptake contributes to hyperglycaemia and induces glomerular hyperfiltration by increasing sodium and water reabsorption in the proximal tubule that, in turn, modifies urine flux at the macula densa. SGLT-2 inhibitors improve glycaemic control and prevent renal hyperfiltration in diabetes. Loss of SGLT-2 transporter function is a benign state characterized by glycosuria. In contrast, mutations of other glucose transporters expressed in the kidney are responsible for severe disorders.

Renal tubular function in children with beta-thalassemia minor.

BACKGROUND: beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. METHODS: The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. RESULTS: There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). CONCLUSION: On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

Juvenile nephronophthisis diagnosed from glucosuria detected by urine screening at school.

We describe the case of an 11-year-old girl in whom glucosuria detected by urine screening at school was the first clue to the diagnosis of juvenile nephronophthisis (JN). On admission, she showed renal failure with combined proximal and distal tubular defects and progressive deterioration of renal function. JN should be considered in children with glucosuria.

Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects.

During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus.

Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition.

Although hypoalbuminemia is a fundamental characteristic of nephrotic syndrome (NS), there are many patients with massive proteinuria that do not develop hypoalbuminemia. We have studied the clinical and biochemical characteristics of 19 patients with persistent massive proteinuria (greater than 5 g/d) and normal serum albumin (group I) in comparison with 16 patients with similar proteinuria excretion, but persistent hypoalbuminemia (group II). Most of group I patients had diagnoses suggesting glomerular hyperfiltration (focal glomerulosclerosis [FGS] associated with vesicoureteral reflux [VUR], reduction of renal mass, proteinuria associated with obesity, sclerotic phase of idiopathic crescentic glomerulonephritis [GN] in contrast with those of group II, in which membranous GN was the most frequent diagnosis. We prospectively investigated differences in the antiproteinuric effect of captopril, an antiotensin-converting enzyme inhibitor (ACEI); after 6 months of treatment, proteinuria decreased clearly in group I (7.1 +/- 1.7 to 3.7 +/- 1.7 g/d; P less than 0.001), whereas no significant changes were observed in group II (8.1 +/- 2.4 to 8.8 +/- 4 g/d). Serum creatinine (Scr) remained stable during captopril treatment in group I, whereas three patients in group II showed a worsening of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal handling of the third (C3) and fourth (C4) components of the complement system in the nephrotic syndrome.

Complementuria is a common finding in patients with heavy proteinuria from a variety of causes, and was detected in 23 out of 34 nephrotic subjects. Mean excretion of C3 and C4 in these patients was 49 +/- 22 and 14 +/- 3 mg/24h, respectively. The renal handling of complement appears to be largely molecular weight (MW) dependent, an inverse relationship between the sieving coefficient and MW of transferrin, IgG, C3, and C4 obtaining, in nephrotic patients irrespective of the nature of their glomerulopathy or degree of renal function. Furthermore, glomerular sieving of C3 and C4 was not significantly different in patients with immune glomerular injury associated with extensive glomerular complement deposition, from that in patients with non-immune glomerulopathy, suggesting that no unique mechanism exists for the transglomerular passage of complement from serum into the urine of the former group. The finding of a large increase of sieving of C3 and C4 in nephrotic patients with end-stage renal failure may indicate a failure by atrophic tubules to reabsorb and catabolize filtered complement.