The effectiveness of steroid therapy for patients with advanced IgA nephropathy and impaired renal function

Background Recent studies have shown that steroid therapy is effective for IgA nephropathy (IgAN) in patients with moderate proteinuria and active histological findings. However, the effectiveness of steroid therapy has not been determined yet in patients with advanced IgAN and impaired renal function.Methods Sixty IgAN patients whose creatinine clearance was under 70ml/min at the time of renal biopsy were studied retrospectively. The patients were divided into two groups according to treatment: a steroid group (n = 20) and a nonsteroid group (n = 40). The mean age was 39.6 ± 14.9 years in the steroid group and 40.6 ± 10.9 years in the nonsteroid group. The mean follow-up period was 4.5 ± 2.2 years in the steroid group and 4.6 ± 2.4 years in the nonsteroid group. Patients with high proteinuria and high histological activity were treated with prednisolone. Clinical and histological findings before treatment and the outcome after treatment were analyzed.Results In the retrospective analysis, the amount of urinary protein excretion before treatment tended to be higher in the steroid group than in the nonsteroid group, but was not significantly different (2.33 ± 1.54 vs 1.39 ± 1.87g/day). Histologically, the percentage of patients with crescent formation, especially that of cellular or fibrocellular crescents, was significantly higher in the steroid group than in the nonsteroid group (17.2 ± 15.9% vs 2.3 ± 4.5%; P < 0.0001). The grades of mesangial cell proliferation (1.65 ± 0.55 vs 1.21 ± 0.47; P = 0.002) and mesangial matrix increase (1.88 ± 0.64 and 1.41 ± 0.67; P = 0.01) were higher in the steroid group than in the nonsteroid group. In the evaluation of the outcome after treatment, the amount of urinary protein excretion at 1 year after treatment had significantly decreased in the steroid group (before treatment, 2.33 ± 1.54g/day; at 1 year, 1.02 ± 0.98g/day; P = 0.003), but the amount remained unchanged in the nonsteroid group (before treatment, 1.39 ± 1.87g/day; at 1 year, 1.28 ± 2.19g/day). The levels of serum creatinine before treatment and at 1 year after treatment were not changed in either of the groups, however, in the nonsteroid group, the level at the final observation was significantly higher than the level before treatment (2.51 ± 3.43 vs 1.27 ± 0.33mg/dl; P = 0.0219).Conclusions In the present study, in advanced IgAN patients whose creatinine clearance was under 70ml/min, steroid therapy effectively reduced the amount of proteinuria and maintained the serum creatinine level, if the treatment was selectively applied to patients with a moderate amount of proteinuria and active glomerular lesions such as cellular and fibrocellular crescents, and mesangial cell proliferation.     

Oral etodolac,a COX-2 inhibitor,reduces postoperative pain immediately after fast-track cardiac surgery

Purpose The present study was designed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor, etodolac, on postoperative pain after fast-track cardiac surgery, and to examine the changes in plasma etodolac concentration after oral administration.Methods Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomly assigned preoperatively in a double-blind fashion to receive either vehicle (n = 15) or etodolac 400mg (n = 15) via a gastric tube at the end of the surgery. Standardized fast-track cardiac anesthesia was used. In both groups, postoperative pain was treated with buprenorphine suppository. Visual analogue pain scores (VASs) were recorded immediately after extubation and at 24h after surgery. Plasma etodolac concentration was measured at 1, 2, and 6h after administration (n = 8).Results No difference was detected in time to extubation between the etodolac group (209 ± 85min, mean ± SD) and the vehicle group (207 ± 98min). VASs were significantly lower in the etodolac (2.3 ± 2.1) vs the vehicle group (5.8 ± 2.0) immediately after extubation (P = 0.009), but no difference was detected in pain scores at 24h after surgery, or in the amount of buprenorphine administered in the intensive care unit (ICU), or in the incidence of side effects. Plasma etodolac concentration was within the pharmaceutically recommended range at 1h, 2h, and 6h after administration.Conclusion The oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects.     

Serum levels of bone GLA protein (osteocalcin,BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegly: Effects of long-term octreotide treatment

Summary We measured serum concentrations of bone Glaprotein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150–450 g/day for 6–33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2±4.2 g/liter versus 8.0±3.3 g/liter, P<0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r=0.67, P<0.001). Also IGF-I concentrations were positively correlated with BGP (r=0.66, P<0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146±46 g/liter versus 127±44 g/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.     

Portal Hypertensive Gastropathy After Surgery for Biliary Atresia

Purpose To clarify the correlation between portal hypertensive gastropathy (PHG) and clinical features after surgery for biliary atresia (BA).Methods Routine upper gastrointestinal endoscopies were done over 3 years in 27 children who underwent surgery for BA. We reviewed the recorded endoscopic findings, and retrospectively diagnosed PHG according to McCormacks criteria. The differences in clinical features, such as endoscopically treated gastroesophageal varices and the results of routine laboratory tests, were compared between the children with PHG (PHG group) and those without PHG (non-PHG group).Results Nine (33%) of the 27 children had PHG. Although there was no significant difference in age between the PHG and non-PHG groups, the frequency of past endoscopic variceal treatments was significantly higher in the PHG group (3.0 ± 3.0 vs 0.6 ± 1.5 times, P = 0.01). The PHG group also had lower white blood cell and platelet counts, at 3008 ± 2411 vs 5527 ± 2938/mm³ (P < 0.05) and 6.0 ± 3.4 vs 13.9 ± 4.7 × 10⁴/mm³ (P = 0.0001), respectively; higher serum aspartate aminotransferase, total bile acid, and total bilirubin levels at 80 ± 31 vs 46 ± 29U/l (P < 0.05), 161 ± 93 vs 64 ± 88U/l (P < 0.05), and 4.8 ± 5.6 vs 1.0 ± 0.8mg/dl (P < 0.01), respectively; and lower prothrombin time, albumin, and cholinesterase levels, at 66 ± 16 vs 79% ± 14% (P < 0.05), 3.6 ± 0.8 vs 4.1 ± 0.5g/dl (P < 0.05), and 2158 ± 925 vs 3376 ± 700U/l (P < 0.001), respectively.Conclusion Portal hypertensive gastropathy was found in 33% of children after surgery for BA. The factors contributing to the development of PHG were frequent endoscopic treatments of gastroesophageal varices, liver dysfunction, and hypersplenism.     

Pharmacokinetic profile of a new fluoride preparation: Sustained-release monofluorophosphate

The pharmacokinetic profiles of a sustained-release monofluorophosphate (MFP-SR) preparation (76 mg) and of plain MFP (76 mg) were compared in six osteoporotic females. These studies were performed in a randomized, crossover, double-blind design to select a preparation that would result in therapeutic serum levels while avoiding high serum peak values. Following a single dose of 76 mg MFP-SR, the serum fluoride levels remained within the accepted therapeutic range (5–10 M/liter) for 24 hours. In contrast, following a single dose of 76 mg plain MFP, serum fluoride levels exhibited a wide circadian fluctuation and serum levels approximately threefold higher than those of the MFP-SR preparation (9.5±1.6 vs 3.5±0.8 M/liter, P<0.005). Compared with plain MFP, the sustained-release MFP had a significantly lower peak concentration (C_max MFP-SR: 10.6 ±3 vs C_maxMFP: 18.9±5 M/liter, P<0.005) and a significantly longer absorption lag time (T_maxMFP-SR 7.3±1.6 vs T_maxMFP: 3.0±0.6 h, P<0.05). Twenty-four-hour urinary fluoride excretion after ingestion of plain or SR fluoride was significantly increased from pretreatment values documenting absorption with either MFP formulation. Our results show that the use of sustained-release MFP preparation that we tested prevents the development of high peak levels associated with the use of plain MFP preparations. Furthermore, a single dose of MFP-SR resulted in serum fluoride levels within the accepted range of 5–10 M/liter for 24 hours.     

β2-microglobulin in Paget's bone disease

On the basis of earlier findings of increased serum ₂-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum ₂-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum ₂-microglobulin concentration was normal (1.49±0.41 mg/liter versus 1.36±0.21 mg/liter in 42 control subjects, P= ns), a finding that contradicts reports in the literature. We found that serum ₂-microglobulin concentration was related negatively and significantly (r²=–0.154, P=0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p =ns). Urinary elimination of ₂-microglobulin was lower in the patients with Paget's disease than in the controls (34±28 versus 120±21 mg/liter, P<0.001). These findings suggest that ₂-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of ₂-microglobulin in bone neoformation.     

Serum calcitonin forms and concentrations in young and elderly healthy females

To further investigate the role of calcitonin (CT) in normal physiology we studied circulating forms and the secretion after calcium clamp in young and elderly healthy females. Heterogeneity of CT in serum was disclosed after immunoextraction, fast protein liquid chromatography, and radioimmunoassay in young (27±3 years; mean±SD, n=6) and elderly females (69±6 years, n=11). Three distinct molecular forms appeared with approximate mol wt of 30, 10, and 3–4 kDa. All young women studied had considerable amounts of circulating monomer-like CT whereas several elderly had undetectable or low levels. The influence of age on basal and calcium stimulated, immunoextracted CT in serum was also studied in young (26±4 years; mean±SD, n=13) and elderly (63±6 years; n=12) healthy females. The calcium stimulation was carried out by means of the standardized calcium clamp method, where calcium was kept on a presettled level at 1.45 mmol/liter (±2%) for 60 minutes. CT was immunoextracted from serum in all series of experiments with a polyclonal antiserum directed against the mid-and carboxyterminal region of the CT molecule, and the amount of extracted CT was determined by radioimmunoassay using another polyclonal antiserum against the carboxyterminal portion. After calcium infusion, the increase in CT was significantly higher in young women than in elderly (P<0.05). At basal conditions, the CT levels were not significantly different but slightly higher in young than in elderly females. In conclusion, several elderly women lack monomer-like calcitonin in serum in contrast to young women. After calcium stimulation of calcitonin, young women had higher serum concentrations than elderly women.     

Preventive treatment of nephrolithiasis with alkali citrate—a critical review

Using the keywords urolithiasis and citrate treatment, nephrolithaisis and citrate treatment, kidney stones and citrate treatment, a Medline search revealed 635 articles published between 1 January 1966 and 1 December 2004. For the present analysis, only studies meeting all of the following criteria were included: (1) publications in English or German, (2) studies on preventive alkali citrate treatment in patients with calcium oxalate, uric acid and infection stone disease, (3) clinical studies including at least ten subjects, and (4) treatment phases of at least 1 week duration. A total of 43 studies met the inclusion criteria and were further subclassified according to intermediate or ultimate endpoints as well as to study design. With stone recurrence as the ultimate endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a reduction in stone forming rate by 47–100%. In four randomized controlled trials including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone-free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5% for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two randomized trials with dissolution/clearance of residual stones as endpoint. Unfortunately, up to 48% of alkali citrate treated patients left the studies prematurely, primarily due to adverse effects such as eructation, bloating, gaseousness or frank diarrhea.     

Diminished Acute Response of Osteoclasts to Calcium Load in Thyroidectomized Patients

To elucidate the role of endogenous calcitonin (CT) in the regulation of bone resorption, we evaluated the acute effects of an intravenous calcium load in nine patients after total thyroidectomy (aged 29.2 ± 8 years) compared with nine healthy subjects. After overnight fasting, intravenous infusions of elemental calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide (-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes after the start of the infusion. At baseline, parameters of calcium and bone metabolism were similar in both groups. A similar increase in S-iCa and decrease in plasma PTH levels were observed in both groups. However, the plasma CT increased significantly by 13 minutes (P < 0.05) and -CTX decreased significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with the baseline) only in the group consisting of healthy individuals. In the thyroidectomized group, the plasma -CTX did not decrease significantly during the first 60 minutes (decrease by only 8% as compared with the baseline) and response to the calcium load was significantly diminished throughout the study period as compared with that of the healthy subjects (P < 0.01). In conclusion, the results indicate that the increased CT secretion is responsible for the rapid initial decrease in the bone resorption following an acute intravenous calcium load.     

Effects of infusion of parathyroid hormone and primary hyperparathyroidism on formation and breakdown of type I collagen

The influence of chronic and acute exposure to parathyroid hormone (PTH) on formation and breakdown of type I collagen, using two recently developed radioimmunoassays for serum PICP (the carboxyterminal propeptide of type I procollagen) and serum ICTP (the carboxyterminal telopeptide of type I collagen), have been evaluated. Fasting morning values were obtained from 18 women with primary hyperparathyroidism (HPT) and an equal number of age-matched, healthy controls. A 24-hour infusion of synthetic human parathyroid hormone (PTH 1-38) was performed in 14 healthy females. The patients with HPT had higher values for serum ICTP than the controls (6.0±3.0 and 4.1±2.1 g/liter; P<0.05), whereas the serum PICP concentrations were not different (170±72 and 151±65 g/liter; n.s.). During infusion of PTH in healthy subjects, there was an increase of the serum ICTP concentrations (from 3.6±1.3 to 4.4±1.8 g/liter; P<0.001) whereas those of serum PICP decreased (from 185±78 to 118±42 g/liter; P0.0001). The increase of serum ICTP during infusion of PTH was positively related to the increase of serum calcium and other indices of bone resorption, i.e., fasting urinary excretions of hydroxyproline and calcium. The decrease of serum PICP was also related to the changes of serum ICTP and hydroxyproline in urine, serum calcium, and alkaline phosphatase but not to osteocalcin, an established marker of osteoblastic activity. The findings support the fact that serum ICTP is a valuable method for evaluating bone resorption and is also easy to perform. Furthermore, the discordant results for the different markers of osteoblastic activity indicat that they reflect different functions of the cell.     

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.     

Effects of nerve stimulation on the spontaneous action potentials recorded in the proximal renal pelvis of the guinea-pig

The effects of nerve stimulation on the electrical and mechanical activity of the smooth muscle of the proximal renal pelvis of the guinea-pig were investigated using standard tension and microelectrode recording techniques. Spontaneous action potentials were deemed to have been recorded from three cell types. (1) pacemaker cells (9 of >120) had membrane potentials (MPs) of -42.1±2.9 mV and fired action potentials of a simple waveform; (2) driven cells (>100) had more stable MPs of -56.1±1.2 mV (n=36) and more complex ureter-like action potentials; (3) the remaining cells had MPs of -45.5±1.7 mV (n=15) and action potentials with a waveform intermediate to groups (1) and (2). Nifedipine (0.1–1 M) and Cd²⁺ (0.1–1 mM) blocked all spontaneous action potential discharge and depolarized the membrane to near -40 mV. Intramural nerve stimulation (10–50 Hz for 1–10 s) increased both the amplitude and frequency of the spontaneous contractile activity, this increase peaked in about 30 s and decayed slowly over several minutes Nerve stimulation depolarized pacemaker and driven cells 9.1±3.5 (n=3) and 1.6±0.7 (n=6) mV, respectively; the frequency of their action potential discharge increased from 7.6±2.7 and 9.9±1.1/min to 17.3±0.5 and 11.1±1.4/min, respectively. The duration of the action potentials in driven cells also increased significantly for several minutes. All these effects were blocked by tetrodotoxin (TTX) (1.6 M). It was concluded that the positive chronotropic and inotropic effects of nerve stimulation on renal pelvis contractility can be correlated with the changes in the frequency and duration of the action potentials recorded in driven cells.     

Atrial natriuretic peptide and cyclic 3′5′-guanosine monophosphate as indicators of fluid volume overload in children with chronic renal failure

Plasma atrial natriuretic peptide (ANP) and cyclic 35-guanosine monophosphate (cGMP) were investigated as indicators of fluid volume overload in children and adolescents with chronic renal failure. Plasma ANP and cGMP were measured in both paediatric patients with chronic renal failure (n=17, mean serum creatinine 371±242 mol/l) and those with end-stage renal disease on haemodialysis (n=18). cGMP was higher in children with chronic renal failure than in 45 healthy controls (1.0±0.4 vs 2.1±0.8 nmol/l,P<0.01), whereas plasma ANP was similar (26.9±9.7 vs 34.0±12.3 pmol/l). Both ANP and cGMP were markedly elevated in children with end-stage renal disease before haemodialysis and fell significantly during dialysis. During dialysis body weight decreased by 1.6±0.7 kg, corresponding to 4.5±2.1% of body weight. Plasma ANP correlated positively with plasma cGMP in haemodialysed patients (r=0.43,P<0.05). Reduction in body weight and in mean arterial pressure correlated more closely with plasma ANP than with cGMP. Therefore, elevation of plasma ANP appears to indicate volume overload in children undergoing haemodialysis, but whether it can be used also in children with chronic renal failure requires further investigation     

Comparison of hemodynamic and anesthetic effects of hyperbaric bupivacaine and tetracaine in spinal anesthesia

Purpose.To compare the anesthetic and hemodynamic effects and the predictive factor of anesthesia level of commonly used preparations of hyperbaric bupivacaine and tetracaine in spinal anesthesia. Methods.Two hundred patients aged 40 to 75 years with ASA physical status I or II were anesthetized spinally via the L4–5 interspace using 0.5% hyperbaric bupivacaine in 7.27% glucose (Bupivacaine group, n = 100) or 0.5% hyperbaric tetracaine dissolved in a 10% glucose solution (Tetracaine group, n = 100) in a lateral position. The volume of anesthetic used was decided by the resident according to the surgical procedure. Patients were returned to the supine position immediately after drug injection. Blood pressure, heart rate, and anesthesia level tested by cold sensation were measured for 30min. Results.Blood pressure and heart rate decreased significantly but without any differences between the groups. The volume of drug used was significantly larger in the Bupivacaine group (2.6 ± 0.5ml) than in the Tetracaine group (2.1 ± 0.4ml) to obtain the same maximum anesthesia level. The time to reach the maximum anesthesia level was significantly longer in the Bupivacaine group (18 ± 7min) than in the Tetracaine group (15 ± 6min). The volume of the drug was the only predictive factor of the maximum anesthesia level in both groups: Level (as expressed by the number of anesthetized segments from S5 to cephalad) = 1.55 × (volume in ml) + 13.06 in the Bupivacaine group, and 2.59 × (volume) + 11.46 in the Tetracaine group. Conclusion.In spinal anesthesia, hyperbaric tetracaine in 10% glucose induced a faster and higher spread of anesthesia than hyperbaric bupivacaine in 7.27% glucose without any differences in hemodynamics.     

Altered glutathione metabolism in the tumor-bearing state

Background: Because glutathione (GSH) appears to be important for tumor growth and many tumors contain the capacity (-glutamyltranspeptidase) to transport GSH, we examined GSH metabolism in MCA sarcoma-bearing rats (TB). Methods: Tumor, liver skeletal muscle, kidney, and serum were collected from 47 MCA sarcoma (TB) rats and 26 normal (CTL) rats. Amino acids, GSH, -glutamylcysteine synthetase (GCS), and -glutamyl transpeptidase (GGTP) were determined. Results: Significant activity of GGTP (117.8±16.0 mU/min/mg protein) was present in tumors. Liver GCS activity (nanomolar per hour per milligram protein) in TB rats (106.6±37.7) was increased (p<0.01) compared with CTL rats (57.5±12.3) and correlated positively with tumor burden (R=0.77). Muscle GGTP was decreased (p=0.001) in TB rats (1.7±1.1) compared with controls (6.8±1.1). Serum GSH concentrations (M) were lower (p<0.05) in TB rats (14.97±1.72) versus control rats (16.82±1.54) and correlated negatively with tumor burden (R=–0.83). Conclusions: In this tumor-bearing model, tumor has significant capacity (GGTP) for the uptake of GSH. Serum GSH is depleted in TB rats and correlates negatively with tumor burden. Liver GCS is increased in TB rats and skeletal muscle GGTP is decreased, which may preferentially benefit the tumor by increasing the bioavailability of glutathione for its own use.Results of this study were presented in part at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, March 17–20, Houston, Texas.     

Renal phosphate leak in patients with idiopathic hypercalciuria and calcium nephrolithiasis

Although urine phosphate loss has been associated with hypercalciuria, it is debated how frequently renal phosphate leak is present in hypercalciuric patients. We reviewed the records of 100 consecutive adult patients who were diagnosed with idiopathic hypercalciuria and calcium urolithiasis, searching for the presence of renal phosphate leak. The renal phosphate threshold, normalized for the glomerular filtration rate (TmPO4/GFR), of the hypercalciuric patients followed a normal distribution and had a good correlation with serum phosphate (r=0.77; p<0.0001). There were no correlations between TmPO4/GFR and urinary calcium or between serum phosphorus and urinary calcium. We found only nine patients (9%) with renal phosphate leak. These patients had a mean TmPO4/GFR of 2.19 mg% (0.70 mmol/l) and serum phosphorus of 2.65 mg% (0.85 mmol/l). Nevertheless, urinary calcium was not significantly different between patients with or without low TmPO4/GFR. We conclude that renal phosphate leak is an infrequent finding in patients with idiopathic hypercalciuria and is not associated with a higher urinary calcium loss.     

Vitamin D receptor initiation codon polymorphism, bone density and inflammatory activity of patients with ankylosing spondylitis

Objectives Osteoporosis is a common finding in ankylosing spondylitis (AS) and may contribute to spinal deformity and bone pain. Bone metabolism as well as inflammatory processes are influenced by the vitamin D receptor gene (VDR). We investigated initiation codon (FokI) and 3UTR (BsmI) polymorphisms of the VDR for whether there could be an association with bone mineral density (BMD) in relation to bone metabolism or inflammatory activity in patients with AS.Methods In this study, 104 patients with AS (m/w 71/33, mean age 41±12 years) were investigated for their lumbar and femoral BMD by DEXA and in part by QCT measurements and compared to 54 healthy controls. Disease activity indices, serum markers of bone metabolism and inflammation were recorded. FokI and BsmI polymorphisms of the VDR were genotyped using genomic DNA from peripheral leukocytes with present or absent restriction sites defined as alleles f and b or F and B, respectively.Results In male AS patients, FokI genotypes were significantly associated with spinal but not with femoral BMD values (P=0.01) as independent predictors of low BMD, which was also influenced by BMI, and inflammatory and pain indices. CRP and ESR values were also significantly associated with FokI genotypes. BMD in female patients showed no significant association with either FokI or BsmI genotypes of the VDR.Conclusion This is the first evidence that the VDR gene may be involved in BMD differences, bone metabolism and inflammatory processes in ankylosing spondylitis. A possible interaction of the vitamin D system, cytokines and bone could define new diagnostic and therapeutic implications in ankylosing spondylitis.     

Phosphorus reduces renal receptivity for parathyroid hormone in rats

Changes in kidney calcium concentration and secreted parathyroid hormone were studied in weanling male rats (n = 12) fed diets containing either 0.5% (n = 6) or 1.5% (n = 6) total phosphorus. Calcium and phosphorus concentrations in the kidney of rats fed a high-phosphorus diet were markedly greater than those in rats fed a control diet. In addition, urinary excretion of phosphorus increased gradually after administration of a high-phosphorus diet, but there was no similar tendency of phosphorus/creatinine excretion, which decreased gradually from the starting day of feeding to the end of the feeding period. The high-phosphorus diet also produced greater serum parathyroid hormone (PTH) without urinary cyclic adenosine monophosphate (cAMP) excretion stimulated by PTH. The mean values of serum 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃) concentrations were significantly increased 1 h after injection of 2.77 g rat PTH(1–34) in all rats. However, in rats fed a high-phosphorus diet, the rise of serum 1,25(OH)₂D stimulated by exogenous PTH was lower than that in rats fed a control diet.     

Risk factors for bleeding complications in percutaneous renal biopsy

Background Among the complications in percutaneous renal biopsy, bleeding is the most frequent and sometimes becomes fatal.Methods We prospectively studied 394 consecutive percutaneous renal biopsies in 359 patients (male/female = 188/171). The mean age of the patients was 44.0 ± 17.2 years. Percutaneous renal biopsies were performed on native kidneys under direct visualization by ultrasound, using an automated spring-loaded biopsy device and a 16-cm 18G needle.Results The most common complication was hematoma (n = 149, 37.8%). De novo macrohematuria was observed in 29 patients (7.4%). Other complications included pain (n = 27, 6.9%), loss of blood (n = 17, 4.3%), and renal dysfunction (increase of serum creatinine more than 0.2mg/dl, n = 9, 2.2%). Although there were no severe complications such as loss of blood requiring a blood transfusion, loss of kidney function, or death, 10 patients had an extended rest period in bed because of moderate complications. Hypertension and amyloidosis had significant influence on the complications.Conclusions For those who are clinically suspected of having amyloidosis or hypertension, more careful biopsy procedures and observations are necessary.     

Hemodynamic and bispectral index responses to tracheal intubation during isoflurane or sevoflurane anesthesia

Purpose.The effects of volatile anesthetics on change in the bispectral index (BIS) due to tracheal intubation are unclear. We investigated hemodynamic and BIS responses to intubation during isoflurane or sevoflurane anesthesia. Methods.After obtaining Institutional Review Board approval and informed consent, we randomly allocated 40 patients of American Society of Anesthesiologists (ASA) physical status I to receive either isoflurane (ISO group; n = 20) or sevoflurane (SEV group; n = 20). The patients were anesthetized with thiamylal and were ventilated with 100% oxygen, using a mask. The inspired concentrations of isoflurane and sevoflurane were gradually increased and maintained at end-tidal anesthetic concentrations of 2 minimum alveolar concentration (MAC) during the study period. Tracheal intubation was performed 15min after the end-tidal anesthetic concentrations had reached 2 MAC. Mean arterial pressure (MAP), heart rate (HR), and BIS were recorded before induction, at the loss of consciousness, before laryngoscopy, and at 1, 3, and 5min after intubation. Results.Anesthesia with 2 MAC volatile anesthetics increased HR in the ISO group, and decreased MAP in the SEV group. The BIS value decreased from 95 ± 3 and 96 ± 2 before thiamylal to 39 ± 9 and 38 ± 10 before intubation in the ISO and SEV groups, respectively. MAP and HR were significantly increased in both groups 1 and 3min after intubation, but BIS remained unchanged. Conclusion.Anesthesia with 2 MAC of isoflurane and sevoflurane was effective to suppress the change in BIS due to intubation but was not sufficient to prevent changes in hemodynamic responses.