Search

Background:We identified two boys with type 3 renal tubular acidosis (RTA) and growth hormone deficiency and we sought to differentiate them from children with classic type 1 distal RTA.Methods:We reviewed all children Results:All children with type 1 RTA reached the 5th percentile or higher on CDC growth charts within 2 years of alkali therapy. Their mean height standard deviation score (SDS) improved from −1.4 to −0.6 SDS and their mean mid-parental height (MPH) SDS improved from −0.6 to 0 SDS after 2 years. In contrast, the boys with growth hormone deficiency had a height SDS of −1.4 and −2.4 SDS after 2 years of alkali and the MPH SDS were both −2.6 SDS after 2 years of alkali therapy. Growth hormone therapy accelerated their growth to normal levels and led to long-term correction of RTA.Conclusions:A child with type 1 RTA whose height response after 2 years of alkali therapy is inadequate should undergo provocative growth hormone testing.

CD44 is observed in ureteric bud structures and is implicated in branching morphogenesis during early mouse renal development. Healthy adult kidney demonstrates minimal CD44, but CD44 is up-regulated in renal diseases. CD44 may mediate binding of calcium oxalate crystals to tubular epithelia via the ligands osteopontin (OPN) and hyaluronan. Because 15% of premature infants develop nephrocalcinosis, developmental tubular CD44 expression might promote nephrocalcinosis. We studied CD44 and OPN immuno-localization in developing human kidney by immunohistochemical analysis. Human renal tissue between 18 and 40 wk of gestation showed CD44 immuno-localization in ureteric buds, with staining decreasing with increasing gestational age; CD44 was rarely observed in developing renal tubules. OPN was diffusely observed in proximal tubules, rarely observed in distal tubules, ureteric buds or metanephric structures. These data support the role of CD44 in early human nephron formation and branching morphogenesis. Rare CD44 staining in developing tubular epithelium suggests no role for CD44 in promoting calcium oxalate adherence to tubular epithelia in premature infants. Immuno-localization of OPN in tubules supports its role in tubular differentiation, but OPN does not seem to be necessary during early nephron formation.

Objective. To study the effect of diuretic drugs on urinary oxalate excretion in premature infants, and to examine the relationship between urinary calcium and sodium excretion in premature infants. Methodology. We measured urinary oxalate, calcium, and sodium excretion in 32 premature infants at approximately 34 weeks gestational age. Seven infants were receiving furosemide, 5 infants were receiving thiazide, 8 infants were receiving furosemide plus thiazide, and 12 infants who were not receiving diuretics served as controls. Results. Urinary oxalate to creatinine ratios in infants receiving furosemide (0.48 ± .26), thiazide (0.54 ± .20), furosemide plus thiazide (0.44 ± .19), and control infants (0.51 ± .43) were similar by analysis of variance (ANOVA). Data expressed as oxalate concentration gave similar results. Urinary calcium to creatinine ratios in infants receiving furosemide (0.81 ± .30), thiazide (0.54 ± .25), furosemide plus thiazide (0.75 ± .49), and control infants (0.37 ± .25) were similar by ANOVA. The urinary calcium concentration in infants receiving furosemide plus thiazide (0.085 ± 0.042 mg/mL) was different from control infants (0.044 ± .023) by ANOVA and Student-Newman-Keuls test. Urinary calcium to creatinine ratio was correlated with sodium to creatinine ratio (r = .751). Conclusion. Urinary oxalate excretion in premature infants is not affected by diuretic drugs. Urinary sodium and calcium excretion are closely linked in sodium supplemented premature infants receiving diuretics. The calciuric effect of furosemide is not decreased by the addition of thiazide in premature infants receiving sodium supplements.

Background Calcium oxalate (CaOx) nephrolithiasis is an adverse effect of Roux-en-Y gastric bypass surgery (RYGB). It is unknown when the increased risk for CaOx stone formation occurs after surgery. Methods We studied 13 morbidly obese adults undergoing RYGB with 24-hour urine collections at 4 weeks before and 1, 2, 4, and 6 months after surgery and computed CaOx relative saturation ratio (RSR) by EQUIL2. Results Eleven patients were female, mean±standard deviation age was 41.1±7.2 years, and none had diabetes or chronic kidney disease. Median (interquartile range) urinary oxalate excretion increased linearly from 12.6 (10.9–37.9) mg/24 hr at baseline to 28.4 (14.4–44.0) mg/24 hr at 6 months (slope = .188; P = .005). CaOx RSR increased significantly at 2 months after RYGB (1.4 [1.2–2.4] to 4.9 [1.7–10.0]; P = .017) and rose throughout the study to 5.7 (3.7–12.2) at 6 months ( P = .001) with a positive linear slope (.255; P = .001). One patient had critical CaOx supersaturation (RSR = 34.7) and severe hyperoxaluria (101.7 mg/24 hr) at 6 months after RYGB. Significant decreases over time were seen in urine volume and sodium and potassium excretion, but no changes were noted in urinary pH, calcium, magnesium, or citrate. Conclusions Our data suggest that CaOx RSR, and thus risk for nephrolithiasis, rises as early as 2 months after RYGB and increases gradually in the first 6 months, largely because of reduced urine volume and increased urinary oxalate excretion. Interventions to reduce CaOx RSR, such as adequate fluid intake and agents to bind enteric oxalate, need to be evaluated in patients at risk for nephrolithiasis after RYGB.

The calcium-sensing receptor (CSR) is a G-protein receptor that plays a critical role in calcium regulation. In the kidney, the CSR regulates calcium reabsorption in the thick ascending limb, where stimulation of the CSR inhibits calcium reabsorption in response to increased calcium in the peritubular fluid. In the collecting duct, apical CSR activation may play a role in osmoregulation, increasing water excretion in response to increased luminal calcium. We studied the ontogeny of the CSR in developing human kidney using immunohistochemical methods. The CSR is first expressed in the S-shaped body in the region destined to form the ascending limb and distal tubule. Other regions of the S-shaped body, as well as ureteric buds, do not express the CSR. The CSR is observed in thick ascending limb as early as 20 wk of development. The CSR is not observed in proximal tubule or collecting duct between 20 and 40 wk of human development. During early human renal development, CSR expression is limited to the thick ascending limb and distal tubule, where this receptor may play a role in calcium homeostasis between 20 and 40 wk of human development.

Objective. To study urinary oxalate excretion in infants fed human milk versus formula, and to compare urinary calcium oxalate and calcium phosphate saturation in premature infants with term infants and adults. Methodology. We measured urinary oxalate-to-creatinine ratio and urinary oxalate concentration in 15 premature infants fed human milk compared to 16 formula-fed premature infants, and in eight human milk-fed term infants compared to 17 formula-fed term infants. We then studied urinary calcium oxalate and calcium phosphate saturations based on our observations of elevated urinary oxalate excretion in premature infants. Urinary calcium oxalate and calcium phosphate saturations were calculated from urinary concentrations of oxalate, calcium, sodium, potassium, chloride, uric acid, magnesium, phosphorus, and urinary pH. We calculated urinary calcium oxalate and calcium phosphate saturations in nine healthy adults and nine formula-fed term infants to establish control values for urinary saturation. Urinary calcium oxalate and calcium phosphate saturations were determined in nine premature infants receiving a glucose and electrolyte solution, 11 premature infants receiving parenteral nutrition, nine formula-fed premature infants, and 11 human milk-fed premature infants. Results. Urinary oxalate excretion was higher in formula-fed compared to human milk-fed premature infants whether expressed as oxalate-to-creatinine ratio (0.32 ± 0.04 versus 0.18 ± 0.03, P < .01) or urinary oxalate concentration (0.047 ± 0.007 versus 0.022 ± 0.002 mg/mL, P < .01). Urinary oxalate excretion was higher in formula-fed term infants than in human milk-fed term infants whether expressed as oxalate-to-creatinine ratio (0.14 ± 0.01 versus 0.07 ± 0.01, P < .01) or urinary oxalate concentration (0.022 ± 0.002 versus 0.012 ± 0.002 mg/mL, P < .01). The urinary calcium oxalate saturation in healthy adults was 2.84 ± 0.79; the value in formula-fed term infants was 2.12 ± 0.31. The urinary calcium oxalate saturation was significantly higher in premature infants receiving formula (15.68 ± 3.15), human milk (15.02 ± 2.27), or parenteral nutrition (11.38 ± 2.56) compared to adults or term infants (P < .01). Urinary calcium oxalate saturation in premature infants receiving a glucose and electrolyte solution (2.45 ± 0.36) was not significantly different from that in adults or term infants. In contrast, urinary calcium phosphate saturation in premature infants as well as term infants and adults was less than 1; precipitation of calcium phosphate is not likely to occur under these conditions. Conclusion. Formula-fed infants have higher urinary oxalate excretion than human milk-fed infants. Premature infants receiving standard nutritional regimens may have urinary calcium oxalate saturation levels at which dissolved calcium oxalate may form nuclei of its solid phase.

Objectives To examine the relationship between urinary pH and metabolic syndrome risk factors along with insulin resistance in obese adolescents, and to evaluate the relationship between other urinary stone-forming and -inhibiting markers and metabolic syndrome. Study design A total of 46 obese adolescents were enrolled. Twenty-four hour and randomly obtained urine samples were analyzed for urinary pH, promoters of stone formation (ie, uric acid, oxalate, and relative saturation ratio of calcium oxalate [RSR-CaOx]), and inhibitors of stone formation (ie, citrate and osteopontin). Other data collected included height, weight, blood pressure, and fasting lipid, insulin, and glucose levels. Results The subjects had a mean age of 14.6±2.0 years and a mean body mass index of 36±6.3 kg/m 2 . Random urine pH and the number of risk factors for metabolic syndrome were negatively correlated ( r =−0.34; P =.02). RSR-CaOx was correlated with both homeostasis model assessment of insulin resistance score ( r =0.38; P r =0.47; P =.001) Conclusion Decreased urinary pH and increased RSR-CaOx are associated with risk factors for metabolic syndrome in obese adolescents.

Osteopontin is an acidic glycoprotein which may prevent nephrocalcinosis and nephrolithiasis by inhibiting the growth and retention of calcium oxalate crystals within the tubular lumen. The purpose of this study was to obtain preliminary data regarding urinary osteopontin in premature infants at risk for nephrocalcinosis. We examined urinary osteopontin concentration in premature infants, term infants and adults, and examined the relationship between urinary calcium and osteopontin concentration in these groups. The urinary osteopontin concentration of 17 premature infants of 3.7 ± 1.2 µg/ml was not significantly different from the urinary osteopontin concentration of 12 term infants of 6 ± 6 µg/ml, while the urinary osteopontin concentration in 23 urine specimens from adults of 27 ± 15 µg/ml was significantly higher than premature infants and term infants (p < 0.05). Urinary osteopontin concentration did not correlate with urinary calcium concentration in premature infants, while there was a correlation between the osteopontin/creatinine ratio and calcium/creatinine ratios in premature infants. Diminished urinary concentration of osteopontin may enhance the risk for nephrocalcinosis in premature infants.

OBJECTIVE: To measure variability among radiologists in the ultrasound diagnosis of nephrocalcinosis in premature infants. METHODOLOGY: In this prospective multicenter study, renal ultrasounds were performed on 54 very low birth weight infants using a 5.0- and 7.5-MHz transducer, and these ultrasounds were read independently by three radiologists. κ coefficients were calculated to assess variability in identification of nephrocalcinosis among the radiologists. RESULTS: The κ coefficient (± confidence intervals) using a 5.0-MHz transducer was 0.143 (0.108, 0.178); using the 7.5-MHz transducer, the κ coefficient was 0.268 (0.243, 0.293). All three radiologists agreed in their identification of nephrocalcinosis on 3 of 54 ultrasounds using a 5.0-MHz transducer; a total of 6 of 54 ultrasounds obtained using a 7.5-MHz transducer were read as positive by all three radiologists. CONCLUSION: There is significant variability among radiologists in the ultrasound identification of nephrocalcinosis in premature infants; a 7.5-MHz ultrasound transducer is associated with less variability in recognizing this lesion.

Oxalate has been implicated in the etiology of nephrocalcinosis in premature infants as well as in the formation of insoluble precipitates in total parenteral nutrition (TPN) intravenous tubing. Oxidation of ascorbate to oxalate, especially in the presence of catalysts such as copper and iron, has been implicated in formation of these precipitates. The purpose of this project was to measure oxalate formation in certain TPN components separately and in combination. Neonatal TPN solution components in combination were infused at 5 mL/h under simulated clinical conditions used in a neonatal intensive care unit. Aliquots were assayed at intervals for oxalate by capillary electrophoresis. Oxalate is present in one TPN mixture at concentrations up to 8 ppm. The addition of ascorbate to an aqueous solution of trace metals may promote oxalogenesis.

URINARY CALCIUM AND SODIUM EXCRETION ARE CLOSELY LINKED IN PREMATURE INFANTS RECEIVING DIURETICS. † 1420

We have described increased urinary oxalate excretion in premature infants(Pediatrics 1989;84:860 and 1994;94:674) and have suggested that calcium oxalate crystal formation plays a role in the development of nephrocalcinosis, which occurs in up to 64% of these infants. Diuretic drug effects on oxalate excretion have been studied in adults but not in premature infants. We measured urinary oxalate to creatinine ratio in 32 VLBW infants at 34 weeks post-conceptual age. All infants were receiving full enteral feedings(Similac, Special Care, Ross Laboratories). Seven infants received Furosemide, five received Thiazide, eight received Furosemide + Thiazide and twelve infants who were not receiving diuretic drugs served as controls. Conclusion: Diuretic drugs do not affect urinary oxalate excretion in premature infants, which is 2-3 fold greater than in term infants.Table