Controlling mesenchymal stem cell differentiation by TGFΒ family members

Mesenchymal stem cells can differentiate into various tissue types including bone, cartilage, fat, and muscle. Transforming growth factor- (TGF) family members, including TGFs and bone morphogenetic proteins (BMPs), play important roles in directing fate decisions for mesenchymal stem cells. TGF can provide competence for early stages of chondroblastic and osteoblastic differentiation, but it inhibits myogenesis, adipogenesis, and late-stage osteoblast differentiation. BMPs also inhibit adipogenesis and myogenesis, but they strongly promote osteoblast differentiation. TGF family members signal via specific serine/threonine kinase receptors and their nuclear effectors, termed Smad proteins. In this review we discuss recent advances in our understanding of the molecular mechanisms by which TGF family members control mesenchymal stem cell differentiation.Presented at the 17th Annual Research Meeting of the Japanese Orthopaedic Association, Aomori, Japan, October 2002     

Effect of hemodialysis and renal failure on serum biochemical markers of bone turnover

The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide (PINP), and -carboxyterminal telopeptide of type I collagen (-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, -CTX, and iPTH. -CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and -CTX were the only markers which correlated with iPTH (P 0.05) and creatinine values (P 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: -CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and -CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.     

Localization of islet-cell hyperplasia: value of pre- and intraoperative arterial stimulation and venous sampling

Arterial stimulation and venous sampling was effective in the localization of -cell hyperplasia of the pancreas in the islets of Langerhans in an 84-year-old woman. The patient presented with repeated episodes of unconsciousness and hypoglycemia. She was first suspected of having insulinoma, but diagnostic imaging failed to reveal any tumors. Arterial stimulation and venous sampling (ASVS) and percutaneous transhepatic portal venous sampling (PTPS) were performed to localize the tumor. By ASVS, increases in immuno reactive insulin (IRI) were noted in renal vein blood samples (because a splenorenal shunt was present) after splenic arterial stimulation and venous sampling, and PTPS revealed a stepup in IRI from splenic venous blood samples. Preoperative diagnosis suggested -cell hyperplasia in the pancreas tail. Intraoperative ultrasound failed to find a tumor. Intraoperative ASVS showed the site of increase IRI as the pancreas tail, so distal pancreatectomy and splenectomy were performed. However, hypoglycemia was observed constantly after this operation. Relaparotomy, causing additional resection, was conducted to confirm the precise location and to remove the residual -cell hyperplasia of the pancreas. At the second resection, the existing part of -cell hyperplasia was confirmed through intraoperative ASVS, and additional resection of the pancreas body and neck was performed. At this time, complete removal of the residual -cell hyperplasia was confirmed through ASVS. The hypoglycemia and impaired consciousness disappeared after the operation, and the patients blood sugar level was maintained at a normal level. Pathological findings revealed islets of Langerhans hyperplasia extending to 1cm in the pancreas tail region. We conclude that pre- and intraoperative ASVS is a useful test for -cell hyperplasia, which is difficult to diagnose through ordinary imaging techniques.     

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline

The newly developed Elecsys -CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum -CTx decreased by 43.2% ± 9.2% (mean ± SD), and 55.1% ± 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% ± 4.1%, 34.1% ± 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% ± 4.1%, 13.1% ± 5.0%, respectively). The percent reduction in serum -CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum -CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys -CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.     

Prediction of chronic renal allograft dysfunction from evaluations of TGFΒ1 and the renin-angiotensin system

Background. Growth factors, cytokines, and the renin-angiotensin system (RAS) are involved in chronic allograft dysfunction. However, it is unclear whether clinical evaluations of TGF1 and the RAS in longterm stable transplant patients can predict the development of chronic allograft dysfunction. Methods. Urinary TGF1 excretion and the response of plasma renin activity (PRA) to angiotensin I converting-enzyme inhibition (ACE-I) were prospectively examined in transplant patients who had had stable graft function (n = 16) for at least 1 year after renal transplantation. Four-year follow-up studies were undertaken to evaluate the impact of these parameters on the development of chronic allograft dysfunction. Results. Urinary TGF1 excretion and PRA response to ACE-I in renal transplant patients who developed chronic allograft nephropathy 4 years after the evaluations (n = 7) were significantly higher and greater, respectively, than these values in those who did not (n = 9; P 0.01). If the cutoff level for urinary TGF1 excretion was 250pg/min, the 4-year positive predictive value (PPV) with respect to the development of chronic allograft nephropathy was 83% and the negative predictive value (NPV) was 78% (sensitivity [sen.], 71%; specificity [sp.], 88%). If the cutoff level for PRA at 60min after ACE-I was 4.0ng/ml per h, the 4-year PPV was 71% and NPV was 75% (sen., 70%; sp., 75%). The stable transplant patients with high TGF1 excretion and exaggerated PRA response showed significantly higher rates of chronic allograft dysfunction than those with low TGF1 excretion and weak PRA response. Conclusions. This study demonstrates that some transplant patients with longterm stable graft function show increases in the activities of the TGF system and the RAS. Evaluations of urinary TGF1 excretion and PRA response to ACE-I present a possibility for predicting the development of chronic allograft dysfunction, with significant 4-year predictive values.     

The effects of prolonged controlled hypotension induced by prostaglandin E1 on renal tubular function

The effects of the prolonged 3-hour and 6-hour controlled hypotension induced by prostaglandin E₁ (PGE₁) on renal tubular function have been comparatively studied with trimethaphan (TMP; 3-hour hypotensive anesthesia) and enflurane deep anesthesia (6-hour hypotensive anesthesia), using the urine N-acetyl--D-glucosaminidase (NAG index) and the serum and urine ₂-microglobulin (fractional clearance of ₂-m; Fc-₂-m) as markers. During 3-hour and 6-hour controlled hypotension PGE₁, NAG index and Fc-₂-m and urine volume could be maintained without remarkable changes. In the group with TPM, NAG index and Fc-₂-m significantly increased. The increasing trend was also noted over time in deep anesthesia with enflurane. On 1st postoperative day, Fc-₂-m significantly increased in PGE₁ group in both 3-hour and 6-hour hypotensive anesthesia, whereas it restored to normal on 2nd postoperative day. Also, in TMP and enflurane deep anesthesia, Fc-₂-m significantly increased on 1st postoperative day. With the latter, significant increase was also observed on 2nd postoperative day. These results suggest that, in 3-hour and 6-hour controlled hypotension induced by PGE₁, renal tubular function is normally maintained and that it is useful for prolonged controlled hypotensive anesthesia. However, further study is necessary because tubular dysfunction might appear on 1st postoperative day.(Fukusaki M, Shibata O, Fujigaki T et al.: The effects of prolonged controlled hypotension induced by prostaglandin E₁ on renal tubular function. J Anesth 4: 197–205, 1990)     

Hypokalemic rhabdomyolysis in a child with Bartter’s syndrome

Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult patients affected by Bartters syndrome and Gitelmans syndrome with rhabdomyolysis due to severe hypokalemia. We report the first pediatric patient with Bartters syndrome in whom rhabdomyolysis developed when her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and potassium prevented tubular damage and acute renal failure. We recommend determining serum creatine phosphokinase in all patients affected by Bartters syndrome and profound hypokalemia.     

Identification of α1-adrenoceptor subtypes in the dog prostate

Summary The ₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to ₁-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [³H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct ₁-adrenoceptor subtypes was suggested: presumably subtypes _1A (high affinity for prazosin and WB4101), _1N (high affinity for only HV723) and _1L (low affinity for the three antagonists) according to the recently proposed ₁-adrenoceptor subclassification. The density of subtype _1L was much higher than that of subtypes _1A and _1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the _1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through _1L subtype -adrenoceptors.     

Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn’s disease

The absorption of bisphosphonates from the gut is poor. The question arises whether the absorption of alendronate, and thus its bioavailability, is further altered by the local inflammatory process in patients with Crohns disease, thereby potentially affecting clinical outcome when used in the treatment of osteoporosis. To address this question, urinary excretion of alendronate was evaluated 3 months and 6 months after start of treatment with oral alendronate at a dose of 10 mg/day in 19 osteoporotic patients with stable Crohns disease, 12 of whom had an intestinal resection. Biochemical parameters of bone turnover and BMD were also measured at start and at 6 months. Thirteen patients had been previously treated with glucocorticoids and five were currently using them. The average 24-h urinary excretion of alendronate was 0.5–0.6% of the dose administered, a figure comparable to that reported for osteoporotic patients without gut pathology. There was a significant decrease from baseline in urine N-telopeptides of collagen cross-links (NTx)/creatinine (60%) associated with an increase in lumbar spine BMD of already 2% after 6 months of treatment. Our data suggest that in patients with Crohns disease, alendronate is adequately absorbed from the intestine and retained in the skeleton. This adequacy is confirmed by appropriate suppression of bone resorption and increase in lumbar spine BMD. These data hold significant implications for the clinical management of patients with Crohns disease and osteoporosis.     

Beneficial Effects of Apolipoprotein A-I on Endotoxemia

Purpose. Although many studies have shown the beneficial effects of lipoproteins on animals with endotoxemia, little is known about the impact of apolipoprotein A-I (apoA-I) on tumor necrosis factor (TNF-) release in response to lipopolysaccharide (LPS). The present study was conducted to determine whether the administration of apoA-I inhibits the release of TNF- and influences the survival rate of rats with endotoxemia.Methods. Forty male Wistar rats were divided randomly into four groups. Rats in the first and second groups were given 1mg/kg LPS intraperitoneally (i.p.) and blood was collected 1h later to measure the serum levels of TNF-. Either 10mg/kg apoA-I or Tris-buffered saline was injected i.p. and the serum TNF- levels were measured again 2h later. Rats in the third and fourth groups were given 5mg/kg LPS. Following the administration of 10mg/kg apoA-I or Tris-buffered saline, animals were observed for 5 days and survival rates were determined.Results. ApoA-I inhibited the release of serum TNF- and improved the survival rates of rats with endotoxemia.Conclusion. The administration of apoA-I suppressed the TNF- release in endotoxemia and decreased the mortality rates of rats.     

Effects of lead on osteoclast-like cell formation in mouse bone marrow cell cultures

To examine an effect of lead (Pb) on the process of osteoclast-like cell formation from its progenitors, we used a mouse bone marrow culture system in which osteoclast-like multinucleated cells (MNCs) were formed in response to bone-resorbing agents. In a 9-day culture period, Pb dose-dependently stimulated MNC formation over the concentration range 2–10 M, whereas at 40 M Pb, MNC formation declined. In an 11-day culture period, MNC formation reached a maximum at 5 M Pb and decreased with increasing concentration of Pb at 10–40 M. Pb-stimulated MNC formation was inhibited by both indomethacin and SC19220, an antagonist of prostaglandin E₂ (PGE₂) receptor. Pb stimulated the production of PGE₂ in marrow cell cultures, suggesting that Pb-stimulated MNC formation is dependent on the production of PGE₂. 3-Isobutyl-1-methylxanthine potentiated Pb-stimulated MNC formation and 2,5-dideoxyadenosine, an inhibitor of adenylate cyclase, inhibited it. A calcium ionophore A23187 increased Pb-induced MNC formation and verapamil, a calcium channel blocker, depressed it. It is possible that a PGE₂-induced increase in the levels of cyclic adenosine 3,5-monophosphate (cAMP) and calcium ions in marrow cells is involved in Pb-induced MNC formation. Pb and parathyroid hormone showed a synergistic stimulation on MNC formation. From these results, Pb is thought to induce osteoclast-like cell formation by a mechanism involving PGE₂ which increases the intracellular levels of cAMP and calcium ions.     

A systematic review of the management of hangman’s fractures

During the past 30 years various treatment protocols for hangmans fractures have been attempted. In order to guide the management of hangmans fractures, different classifications have been introduced. However, opinions on operative or nonoperative treatment have not yet been solidified. To evaluate both conservative and operative management of hangmans fractures in the published literature and to provide appropriate guidelines for treatment of hangmans fractures, a systematic review of the literature regarding the management of hangmans fractures was performed. An English literature search from January 1966 to January 2004 was completed with reference to treatment of hangmans fractures. The classification for treatment guidance from the literature was also reviewed. Regarding a primary therapy for hangmans fractures, there were 20 papers (62.5%) that advocated for a conservative treatment and 11 of the remaining 12 papers suggested that conservative treatment was suitable for some stable fractures. The classification of Effendi et al. modified by Levine and Edwards was used widely. Most hangmans fractures could be managed successfully with traction and external immobilization, especially in Effendi Type I, Type II and Levine-Edwards Type II fractures. It is necessary for Levine-Edwards Type IIa and III fractures to be treated with rigid immobilization. Only for some stable Type I and Levine-Edwards Type II injuries, nonrigid external fixation alone was sufficient. Rigid immobilization alone was necessary for most cases. Surgical stabilization is recommended in unstable cases when there is the possibility of later instability, such as Levine-Edwards Type IIa and III fractures with significant dislocation. The classification system proposed by Effendi et al. and modified by Levine and Edwards provided a clinically reasonable guideline for successful management of hangmans fractures.     

Decreased osteoprotegerin and increased bone turnover in young female patients with major depressive disorder and a lifetime history of anorexia nervosa

Low bone mineral density (BMD) is a frequent, often persistent complication in patients with major depressive disorder (MDD) and anorexia nervosa (AN) that increases the risk of pathologic fractures. The pathogenetic process underlying osteopenia in MDD and AN is still unclear, although several factors, including a dysbalance of cytokines, are associated with loss of bone mass. Alterations in the serum levels of cytokines have been observed in patients with MDD, AN, and other psychiatric disorders. Therefore, we examined serum levels of cytokines, markers of bone turnover, and BMD in 13 patients with MDD and a lifetime history of AN. Bone turnover markers (osteocalcin and C-terminal degradation products of type I collagen) and tumor necrosis factor (TNF-) in patients were significantly increased compared with those of the control group. Osteoprotegerin (OPG) in patients was significantly decreased. Eight of 13 patients (62%) displayed osteopenia at the lumbar spine. TNF- correlated significantly with C-terminal degradation products of type I collagen, an osteoclastic marker, but significantly negatively with OPG. Our data suggest that TNF- and OPG may play a role in the pathogenetic process underlying osteopenia in these patients.     

The changes in arterial keton bodies during upper abdominal surgery

The relationship between the arterial keton body ratio (AKBR: acetoacetate/-hydroxybutyrate) and the plasma hormone activities were studied under a general anesthesia using enflurane group (group G) and a GO + Epidural group (group E) with continuous glucose loading (10g·hr^–1) during partial gastrectomy. In both groups, the AKBR increased significantly during the operation. The plasma insulin activity was significantly positively correlated with the AKBR and it was negatively correlated with log (-hydroxybutyrate) in both groups. We could not find any significant difference of the AKBR between group G and group E. Our results indicate that the plasma insulin activity affects the arterial keton body ratio and that the AKBR must be evaluated considering the plasma hormone activity, especially insulin activity during the operation.(Ogata M, Obata K, Matsumoto et al.: The changes in arterial keton bodies during upper abdominal surgery. J Anesth 4: 131–137, 1990)     

Pied plat réductible traité par la vis d’expansion du sinus du tarse. À propos de 30 cas

Résumé: Dans un pied plat, lobjectif de larthrorise subtalaire est de rétablir des rapports appropriés entre le talus et le calcanéum par limplantation dun espaceur. Le but de cette étude est dévaluer les résultats de la vis dexpansion du sinus du tarse ainsi que le devenir des pieds au recul. Matériel: Trente patients porteurs de pied plat réductible et symptomatique ont participé à cette étude. Il sagissait de 28 hommes et de 2 femmes. Lindication opératoire a été posée sur la coexistence dun handicap fonctionnel liée à la douleur et de léchec du traitement orthopédique. Lâge moyen au moment de lintervention était de 21 ans. Langle de Djian-Annonier était de 134°. Méthodes: Il sagissait dune étude rétrospective. Létat fonctionnel global était évalué au moyen du score de Kitaoka. Résultats: Le recul moyen était de 4 ans. Plus aucun patient ne portait de chaussure orthopédique. Nous navons pas de remaniements articulaires dégénératifs au recul. Le résultat global était: 20 très bien, 4 bien, 2 passable, 4 mauvais. Discussion: Larthrorise par espaceur du sinus du tarse est un geste techniquement simple permettant une correction podoscopique significative du pied plat qui se maintient à la révision. Conclusion: Cette technique simple permet dobtenir des résultats anatomiques et fonctionnels satisfaisants.* Les figures de cet article sont disponibles en couleur sur le site springerlink.com     

Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery

An investigation was carried out on the productivity of cytokines and active-oxygen by peripheral blood cells during the pre- and post-operative periods. While the preoperative production of tumor necrosis factor (TNF) and interleukin-l (IL-1) was elevated, that of lymphotoxin (LT) and interferon- (IFN-) were slightly suppressed. In the postoperative period the peak TNF and IL-1 and active-oxygen productivity was elevated, while LT and IFN- productivity was suppressed in patients with an intraoperative bleeding volume of more than 1,000 ml compared to those with that of less than 1,000 ml. Thus, stress stimulates the TNF and IL-1 and active-oxygen producing system, that is, the macrophage-neutrophil system, and suppresses the LT and IFN- system, being, the inflammatory helper T cell system, in the early postoperative period.     

Association of meningiomas with dural “tails”; Surgical significance

Summary Intracranial meningiomas are characteristically benign tumours with a tendency to recur following surgical resection. Our group is investigating the pathogenesis of meningioma recurrence. In our initial studies we identified two cases of dural tails associated with intracranial meningiomas. Gadolinium-enhanced magnetic resonance images were utilized to identify the dural tails preoperatively. These images aided us in performing a more complete surgical resection of the meningiomas. Histopathological confirmation of meningotheliomatous cell infiltration into the dural tails demonstrates their surgical significance.     

The Role of Transforming Growth Factor α Formulation on Aspirin-Induced Ulcer Healing and Oxidant Stress in the Gastric Mucosa

Purpose Transforming growth factor (TGF) accelerates wound healing, especially in gastric ulcers. Transforming growth factor can be affected by acid and pepsin in the gastric juice. Oxidative stress also plays a role in the formation of gastric lesions. This study was designed (1) to investigate the effects of microemulsion dosage form on the healing of gastric ulcers, and (2) to determine the relationship between oxidative mechanisms and TGF- during ulcer healing.Methods Gastric ulcers were induced in Wistar rats (male, 200 ± 25g), by 150mg/kg acidified aspirin application. The animals were divided into five groups consisting of 7–11 animals. The rats were killed after ulcer induction with aspirin (acute ulcer), or 2 days after ulcer induction (chronic ulcer), or after the daily application of microemulsion and TGF- for 2 days. The ulcer area was measured planimetrically. Thiobarbituric acid reactive substance, glutathione, and gastric mucus levels of tissues were measured by spectrophotometric methods. The total nitric oxide level was measured by a VCl₃ / Griess assay. Statistical comparisons were made by an analysis of variance and the Mann-Whitney U-test.Results The ulcer area and malondialdehyde level of gastric tissue both decreased and the glutathione level increased to intact gastric tissue levels, while the mucus and total nitric oxide levels increased significantly after the application of intragastric TGF-.Conclusion These findings suggest that TGF- accelerates the healing process after aspirin-induced gastric injury, and a relationship was observed between this application and the oxidative reactions.     

Dexamethasone regulates IL-1β and TNF-α-induced interleukin-8 production in human bone marrow stromal and osteoblast-like cells

We have investigated both constitutive- and cytokine-induced secretion of interleukin-8 (IL-8) and its regulation by dexamethasone and 17-estradiol in normal human bone marrow stromal (HBMS), osteoblast-like cells (hOB), and osteosarcoma MG-63 cells. Although HBMS cells secrete low levels of IL-8 constitutively, treatment with IL-1 and tumor necrosis factor- (TNF-) induced IL-8 secretion. Their effects were synergistic but IL-8 production was not affected by 17-estradiol. Human osteosarcoma MG-63 cells also secreted low levels of IL-8 constitutively; the production was induced by IL-1 and TNF- and was also not affected by 17-estradiol. The magnitude of the response to cytokine stimulation of IL-8 in MG-63 cells was much lower than that of HBMS and hOB cells, indicating differences in response in normal and osteoblastic osteosarcoma cells. Dexamethasone (10^-7 M) significantly inhibited IL-1 plus TNF- stimulated IL-8 production in HBMS, MG-63, and hOB cells. The accumulated results demonstrate that IL-8 is secreted by HBMS, MG-63, and hOB cells, suggesting that IL-8 may play a role in the regulation of bone cell function. These data also emphasize the importance of glucocorticoids in controlling cytokine secretion in HBMS, hOB, and MG-63 cells.     

Serum α1-microglobulin and β2-microglobulin for the estimation of fetal glomerular renal function

As proteins cannot cross the placenta levels of the microproteins ₁-microglobulin (₁MG) and ₂-microglobulin (₂MG) can be used to assess fetal glomerular renal function. ₁MG, ₂MG and creatinine were routinely determined in cord and maternal blood of 133 newborns [gestational age (GA) 25–42 weeks]. Twenty-nine patients with suspected impaired maternal or fetal renal function were studied separately and two fetuses were studied in utero. The mean fetal ₂MG concentration fell from 3.87±0.56 mg/l in the 25–31 weeks GA group to 2.60±0.50 mg/l in the mature newborn group. ₁MG concentration fell from 3.10±0.51 to 2.25±0.49 mg/dl. In contrast, the mean maternal ₁MG concentration rose from 1.73±0.69 mg/l in the 25–31 weeks GA group to a mean of 1.83±0.48 mg/l in the mature newborn group; ₁MG rose from 3.96±0.58 to 4.33±1.6 mg/dl. Maternal and fetal creatinine levels were identical. Fetal microprotein levels fall during intra-uterine development as glomerular filtration rate (GFR) rises. There is no correlation between cord blood and maternal ₁MG or ₂MG concentrations. In 13 children with urological anomalies only 1 had elevated microprotein levels and he later developed renal insufficiency. Determination of microprotein levels in fetal serum can be used to detect severe renal function disturbances and to estimate GFR independently of maternal renal function.