Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE_Na) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2±14.0 pM/ml) than in group I (50.6±4.2 pM/ml), group II (49.6±3.7 pM/ml) and group III (50.6±3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1±33.9 pM/mg) than in the three study groups (52±7.6 pM/mg, 58.6±7.5 pM/mg and 44.2±6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE_Na and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.     

Adrenomedullin and total nitrite levels in children with Henoch-Schönlein purpura

Nitric oxide (NO) is synthesized from endothelium and has an important role in the control of vascular tonus. Adrenomedullin (AM) is a potent vasodilator, and cytoprotective peptide is produced not only in adrenal medulla, but also in the vascular smooth muscle and endothelial cells. To investigate the endothelial synthesis of AM and NO, and endothelial injury in Henoch-Schönlein purpura (HSP), we measured their levels in 16 children with HSP, who were evaluated during the acute and remission phases, and compared with 12 healthy controls. Plasma AM levels (pmol/ml) were significantly higher in acute phase children (46.87±11.49) than in those in remission (35.59±12.39, p<0.01) and controls (30.70±9.12, p<0.001). Similarly, plasma total nitrite levels (mol/l) were higher in acute phase patients (47.50±12.30) than in those in remission (35.94±10.08, p<0.005) and controls (34.56±11.51, p<0.05). Urinary excretion of AM (pmol/mg creatinine) was higher in acute phase patients (53.85±23.22) than in remission patients (29.97±9.33, p<0.01) and controls (37.43±15.78, p<0.05). Patients had increased urinary nitrite excretion (mol/mg creatinine) in acute phase (2.39±1.18) compared to those in remission (1.53±0.90, p<0.05) and controls (1.05±0.61, p<0.005). There was no significant difference between remission phase and controls in AM and nitrite levels (p>0.05). This study concluded that AM and NO may have a role in the immunoinflammatory process of HSP, especially in the active stage, although whether this perpetuates, or protects against, further vascular injury is not clear. Further studies are needed to clearly establish the roles of AM and NO in the pathogenesis of HSP.     

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis

Background: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. Methods: Plasma levels and urinary excretion of tumour necrosis factor-&agr; (TNF-&agr;), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 15 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. Results: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-&agr; (9.27±3.19% vs 0.58±0.02%, P<0.01), IL-6 (120.79±65.83% vs 1.89±0.34%, P<0.01) and increased fractional excretion of IL-8 (23.34±6.38% vs 2.56±1.07%, P<0.01) and sVCAM-1 (0.81±0.33% vs 0.03±0.02%, P<0.01) compared with controls. Urinary excretion of TNF-&agr; and IL-6 and fractional excretion of TNF-&agr;, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-&agr; (20.52±2.01 pg/ml vs 12.33±0.23 pg/ml, P<0.05) and sVCAM-1 (1537.88±276.36 ng/ml vs 692.26±44.42 ng/ml, P<0.05) and increased urinary excretion of TNF-&agr; (2.81±0.51 &mgr;g/mol creat vs 0.98±0.05 &mgr;g/mol creat, P<0.01), IL-8 (35.78±14.03 &mgr;g/mol creat vs 12.46±5.19 &mgr;g/mol creat, P<0.05) and sVCAM-1 (48.98±20.20 &mgr;g/mol creat vs 2.92±1.35 &mgr;g/mol creat, P<0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-&agr; (18.10±0.57 pg/ml vs 12.33±0.23 pg/ml, P<0.05). Conclusions: Urinary excretion and fractional excretion, but not plasma levels of selected proinflammatory cytokines (TNF-&agr;, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.     

Chlamydial infection of the urinary tract in children and adolescents with hematuria

Urogenital infection with Chlamydia trachomatis in adults and adolescents is a common sexually transmitted disease. The purpose of this study was to investigate whether isolated microhematuria in children and adolescents is associated with Chlamydia trachomatis infection of the urinary tract. The study group included 37 children and adolescents with isolated nonglomerular microhematuria. Urethral smears for the isolation of Chlamydia trachomatis in cell culture were taken at the time of cystourethroscopy from all patients. Polymerase chain reaction (PCR) for the detection of chlamydial DNA in urine was carried out in 25 of 37 (68%) patients and direct immunofluorescence (DIF) of urine in 16 of 37 (43%) patients. The control group included 33 children and adolescents without hematuria; PCR and DIF of urine were carried out in all controls. Chlamydia trachomatis infection of the urinary tract was confirmed in 8 of 37 (22%) patients in the study group, and in none in the control group (0 of 33, P<0.001). Further studies of larger groups of patients should be conducted, before recommending testing for Chlamydia trachomatis infection of the urinary tract in children and adolescents with unexplained microhematuria. Received: 26 January 2000 / Revised: 26 April 2000 / Accepted: 2 May 2000     

Antiproteinuric effect of angiotensin-converting enzyme inhibition and C5b-9 urinary excretion in membranous glomerulonephritis

Background: Angiotensin-converting enzyme (ACE) inhibitors have an antiproteinuric effect in membranous glomerulonephritis (MGN). However, no studies hae investigated whether this antiproteinuric effect is influenced by urinary C5b-9 excretion, a marker of immunological activity in this disease. Methods: Eleven patients with biopsy-proven MGN were treated with captopril for 8 weeks. The evolution of several clinical and biochemical parameters, including 24-h urinary protein excretion was evaluated every 4 weeks. Urinary C5b-9 excretion was measured at the onset and at the end of captopril treatment. Results: Patients with MGN had significantly higher C5b-9 excretions than a group of 14 healthy controls (89±23 vs 3.7±1.4 ng/mg UCr; P<0.001). A significant correlation was found between urinary C5b-9 and the magnitude of proteinuria, both at the onset and at the end of treatment. After 8 weeks of captopril treatment, proteinuria had decreased from 8±1.8 to 5.2±1.3 g/day (P<0.05). Four weeks after captopril discontinuation, proteinuria rose to 7.3±1.7 g/day (P<0.05). A marked variability in the antiproteinuric response was observed, ranging from 0 to 85% with respect to baseline values. No correlation between decrease in proteinuria and baseline urinary C5b-9 levels was observed. Several patients with elevated urinary C5b-9 levels had captopril-induced decrease in proteinuria. Conclusions: ACE inhibition induces an antiproteinuric effect in patients with MGN. The urinary C5b-9 excretion does not predict the magnitude of this response.     

Bone alkaline phosphatase in children with chronic renal failure

Background: With the introduction of a new immunoradiometric assay based on two monoclonal antibodies (Tandem®-Ostase, Hybritech) the determination of bone alkaline phosphatase (BAP) to evaluate bone metabolism in chronic renal failure has become easier and more valid. Subjects and methods: Using this test we investigated BAP in a total of 90 paediatric patients, 42 (9.2±5.5 years) with chronic renal failure on conservative treatment, 22 (9.5±5.4 years) under chronic dialysis, and 26 (16.2±5.9 years) after renal transplantation, compared to 203 controls (10.1±5.7 years). Results: The physiological age dependency found in controls including two peaks during infancy and puberty was distinctly disturbed in chronic renal failure. However, in patients BAP significantly correlated with height velocity rather reflecting the last 6 (r=0.56 P<0.001) than the last 12 months. Although BAP correlated well with total alkaline phosphatase (TAP; r=0.95 P<0.001), a significant correlation with the serum level of the intact parathyroid hormone could only be detected for BAP (r=0.45 P<0.001) but not for TAP (R=0.19 N.S.) Furthermore, BAP positively correlated with trabecular (n=40; r=0.40 P<0.05) and inversely with cortical bone density (n=19; r=-0.58 P<0.01) but no relationship was found with conventional X-ray. Conclusion: BAP determined by the new radioimmunoassay seems to represent an additional diagnostic tool to assess growth and bone turnover in paediatric patients with chronic renal failure that is complementary to the information provided by X-ray and total alkaline phosphatase. Key words: bone alkaline phosphatase; children; chronic renal failure      

Interleukin-6 and interleukin-8 in the urine of children with acute pyelonephritis

Interleukin-6 (IL-6) and interleukin-8 (IL-8) are important mediators of the inflammatory response in serious bacterial infections. We studied the levels of these two cytokines (standardised for urinary creatinine) in the urine of infants and children during and 6 weeks after acute pyelonephritis and in non-renal febrile controls and healthy children without apparent infection. IL-6 was detected in the urine of 52% of children with pyelonephritis compared with 15% of other children (P<0.001). The median urinary IL-6 level in acute pyelonephritis was 4 pg/mol compared with undetectable levels in the control group (P<0.001). IL-8 was detected in 98% of children with pyelonephritis and 42% of other children (P<0.001). The median concentration of IL-8 was 188 pg/mol in pyelonephritis; it was undetectable in controls (P<0.001). IL-8 levels were higher in children less than 1 year of age (P<0.001).     

Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans

Background: Inhibition of nitric oxide (NO) synthesis has antinatriuretic and antidiuretic effects. Limited information is available on the role of NO in tubular sodium transport in the human kidney. Methods: We studied nine healthy, sodium-replete males with clearance techniques during maximal diuresis. N^G-monomethyl-L-arginine (L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was infused for 3 h, to achieve steady-state inhibition of NO synthesis. Data were compared with a time control study. Results: The effects of L-NMMA were quickly established and persisted through the entire infusion period. Mean arterial pressure increased slightly from 85±3 to 91±3 mmHg (P<0.05). Renal plasma flow decreased substantially, and glomerular filtration rate slightly. Large decreases in absolute sodium excretion, from 79&;plusmn;10 to 34±5 &mgr;mol/min (P<0.01), and fractional sodium excretion, from 0.5±0.0 to 0.3±0.0% (P<0.01), were associated with significant reduction in fractional lithium excretion (P<0.05) and maximum urine flow (P<0.01). Minimal urine sodium concentration decreased from 5.8±0.04 to 3.9±0.4 mmol/l (P<0.01) whereas minimal urine osmolality increased (P<0.05). Plasma renin activity, aldosterone and atrial natriuretic peptide levels did not change, whereas urinary excretions of guanosine 3'5'-cyclic monophosphate and of nitrite plus nitrate decreased slightly. Conclusions: Inhibition of endogenous NO synthesis in humans to an extent that raises blood pressure only mildly causes antinatriuresis, that can be attributed to increases in sodium reabsorption both at proximal and distal nephron sites. In addition, renal diluting capacity decreases. The effects in the diluting segment have not been reported before, and may be due to medullar vasoconstriction, similar to that described for angiotensin II.     

Renal tubular dysfunction in fetal alcohol syndrome

Renal function was evaluated in six patients with fetal alcohol syndrome (FAS) and eight control subjects before and after fluid restriction and acute acid loading. Baseline serum electrolytes, creatinine clearance, fractional sodium excretion, tubular reabsorption of phosphate, urine and blood pH and osmolalities, plasma renin activity, and plasma aldosterone level were normal in all subjects, but fractional potassium excretion (FE_K) was lower in FAS patients than in control subjects (P<0.001). Despita equivalent plasma osmolalities (295±3 vs 293±2 mosmol/kg,P=0.2), the maximum urinary osmolality after 12 h of water deprivation in patients with FAS was significantly lower compared with controls (560±107 vs 965±77 mosmol/kg;P<0.001) and increased to only 578±101 mosmol/kg after vasopressin administration. After ammonium chloride loading, minimum urine pH was significantly higher in patients than in controls (5.7±0.17 vs 4.81±0.19;P<0.001). Net acid excretion and FE_K were also lower in patients than in controls (102±11 vs 139.6±11.3 Eq/min per 1.73 m² and 23.5±1.3 vs 29±1.6%, respectively;P<0.001). The data indicate a subclinical renal tubular defect in urine concentration and acidification in patients with FAS.     

Low-density lipoprotein subfraction profiles in chronic renal failure

Background: Small low-density lipoprotein (LDL) particle size, a newly recognized risk factor for cardiovascular disease in the general population, is frequently associated with hypertriglyceridaemia, the predominant plasma lipid abnormality present in uraemia. Methods: Plasma lipids and LDL subfraction profiles were examined in 33 non-dialysed patients with chronic renal failure (predial), 40 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL subfractions separated by gel electrophoresis were scored by densitometric analysis (higher scores indicate profiles comprising smaller particles). Results: All groups with renal failure had significantly elevated (mean±SD) LDL scores (predial 1.36±0.6, CAPD 1.71±0.9, HD 1.68±0.9, RTR 1.92±0.8 vs control 0.87±0.4, all P<0.001), this being the only lipid abnormality detected in the predialysis patients. In CAPD and HD patients, LDL scores were associated with serum triglyceride (r=0.81, P<0.0001 and r=0.70, P<0.01 respectively), cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r=-0.43, P<0.01 and r=-0.51, P<0.01), whilst no such relationship was seen in the predialysis and RTR groups, suggesting that other factors were important. Conclusions: The presence of small LDL particles appears to be an early and unexplained feature of the uraemic dyslipidaemia. This abnormality persists after renal transplantation and may represent an important atherogenic risk factor. Key words: LD subfractions; renal failure; transplants      

Urinary tract infection caused by <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> and <Emphasis Type="Italic">Haemophilus parainfluenzae</Emphasis> in children

There are few reports on urinary tract infections caused by Haemophilus influenzae or Haemophilus parainfluenzae in children. The true incidence is not known, since bacteria of Haemophilus species do not grow in standard urine culture media. With the objective of investigating the occurrence and character of urinary tract infections (UTIs) caused by Haemophilus bacteria in children, we searched the files of our UTI clinic. Over a 24-year period 36 children with Haemophilus spp. bacteriuria were identified out of a total of more than 5,000 UTI episodes. There was a significant gender difference in that Haemophilus influenzae dominated in girls and Haemophilus parainfluenzae in boys. With one exception, all children had important urinary tract abnormalities, such as malformation, gross reflux or bladder dysfunction. Permanent renal damage was seen in 25. We conclude that growth of Haemophilus bacteria in urine is associated with serious urinary tract abnormalities. The inability of bacteria of the Haemophilus species to grow in standard media commonly used for culture of uropathogens suggests that the true frequency of these strains as a cause of urinary tract infections is underestimated.     

Albuminuria after fetal pancreatic islet transplantation: a 10-year follow-up

Aim of the study: The prevention of diabetic nephropathy is as yet an unresolved issue. The aim of our study was to assess the effects of transplantation of long-term cultured and cryopreserved fetal pancreas islets on metabolic control and the development of diabetic nephropathy. Methods: Serum C-peptide, glucose, HbA1c, insulin requirements, urinary albumin excretion rate, and blood pressure of 10 insulin-dependent diabetic patients after transplantation were compared with a group of 27 insulin-dependent diabetic controls on insulin therapy only during a 10-year follow-up. Results: In the first year after transplantation mean insulin requirement decreased from 53.6±2.2 to 35.8±1.2 units. C-peptide levels appeared (0.55±0.08 ng/ml) and remained detectable throughout the follow-up.. Blood glucose and HbA1c were significantly (P<0.05) lower than in the controls. Mean albumin excretion rates of the transplant and the control groups during the follow up were 18.8±8.5 and 11.7±2.0, 16.6±6.6 and 14.0±2.3, 15.0±5.0 and 15.1±2.7, 15.3±7.5 and 20.4±4.2, 19.8±6.2 and 36.7±11.1, 11.7±3.6 and 51.3±14.6, 14.1±4.2 and 71.4±23.1, 22.7±8.6 and 92.0±28.1, 18.0±5.9 and 107.6±35.6, 21.7±11.0 and 101.5±29.2 &mgr;g/min respectively. From the 6th year the difference between the two groups was significant (P<0.001). In the transplant group initial mean systolic and diastolic blood pressure values were 132.0±3.3 and 81.5±1.5 mmHg, in the controls 130.4±3.4 and 79.6±1.6 mmHg respectively. Significant changes (P<0.05) of blood pressure during the follow-up or differences between the two groups were not observed. Conclusions: We conclude that fetal islet transplantation is effective in achieving good long-term diabetes control and in the prevention of diabetic nephropathy. Key words: albuminuria; diabetic nephropathy; diabetes mellitus; diabetes control; fetal pancreas islet transplantation      

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245±101 mg/m² per hour, 6.6±1.2, and 1.5±1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly (P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8±1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m² per hour, one had proteinuria of >20 mg/m² per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.     

Microalbuminuria in Children with Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is a common congenital anomaly of the urinary tract that may be inherited. Reflux of infected urine may cause scarring in susceptible kidneys with the potential to compromise renal function. The aim of the study was to evaluate the possible influence of different grades of VUR on glomerular damage using microalbuminuria as a parameter. Children with VUR detected by voiding cystourethrography (VCUG) were investigated. According to the grade of VUR, patients were separated into three groups. The first group included 12 children with VUR grade I–II. The second group consisted of 12 children with grade III of VUR. Patients with VUR grade IV–V (n = 11) were members of the third group. The control group consisted of 17 healthy children. Microalbuminuria was examined in samples of morning urine specimens using a microalbumin/creatinine reagent kit. Serum urea, creatinine levels and creatinine clearance (CCR) were measured as markers of renal function. The mean value of microalbumin excretion in the third group showed a statistically significant increase (p < 0.001) compared to all other groups. CCR in the third group was statistically significantly decreased (p < 0.05) in comparison to the group of healthy children. There were no statistically significant changes of microalbumin excretion and CCR in the first and second group compared to control values. We discussed the presence of microalbuminuria and decrease of CCR in children with high grade of VUR as a possible consequence of retrograde urine flow (intrarenal reflux), glomerulosclerosis, and consecutive hyperfiltration.     

Contrasting renal effects of nicotine in smokers and non-smokers

Background: Cigarette smoking is associated with acute increase in arterial pressure due to systemic vasoconstriction and decreased skin and coronary blood flow. Virtually all cardiovascular effects of cigarette smoking are due to nicotine. However, whether nicotine also affects the renal circulation and function in humans is at present unknown. Methods: In the current study the acute effects of a 4-mg nicotine gum on arterial pressure, heart rate as well as renal haemodynamics and function were assessed in non-smokers and chronic smokers. Results: In non-smokers, mean arterial pressure (+8±1 mm Hg, P<0.001) and heart rate (+13±3 beats/min, P<0.001) increased whereas effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) decreased by 15±4% and 14±4% respectively; in addition, urinary cyclic GMP decreased by 51±12% in response to nicotine administration. In smokers, mean arterial pressure and heart rate increased similarly; however, in contrast with non-smokers, ERPF and GFR remained unchanged whereas urinary cyclic GMP rose by 87±43%. Changes in ERPF induced by nicotine were positively correlated with changes in urinary cyclic GMP. Conclusions: These findings indicate that nicotine administration is associated with renal vasoconstriction in healthy non-smokers, possibly through alteration of a cyclic-GMP-dependent vasoactive mechanism. Tolerance to the renal effect of nicotine was observed in chronic smokers, despite the maintenance of the systemic response to nicotine.     

Quantification of proteinuria in children using the urinary protein-osmolality ratio

A prospective study was conducted to determine the correlation of early morning urinary protein/osmolality ratio (mg/l/mosmol/kg) with 24-h urinary protein excretion (mg/m²/day). Study patients consisted of 53 children (aged 1 month to 15 years). Early morning urine samples and 24-h urine samples were collected and analyzed. In group 1 (children without proteinuria), early morning urinary protein/creatinine ratio (Uprot/Ucr, mg/mg) was 0.061±0.011 and the protein/osmolality ratio (Uprot/Uosm, mg/l/mosmol/kg) was 0.073±0.014. Twenty-four hour urinary protein excretion in group 1 had no significant correlation with Uprot/Ucr or Uprot/Uosm. In group II (children with proteinuria), Uprot/Ucr was 5.78±1.10 and Uprot/Uosm was 4.42±1.34. Twenty- four hour urinary protein excretion in group 2 was 1483.6±303.7 mg/m²/day and its correlation with both Uprot/Uosm and Uprot/Ucr was highly significant (r= 0.87, P<0.001 and r=0.88, P<0.001, respectively). The accepted nephrotic level of proteinuria of 40 mg/m²/h coincides with a Uprot/Uosm ratio of 1.9. In conclusion, early morning urinary Uprot/Uosm is a simple and potentially useful test for 24-h urinary protein excretion, and possibly could be used safely for the assessment of the degree of proteinuria in children. Received: 13 April 1999 / Revised: 23 February 2000 / Accepted: 15 August 2000     

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study

Background: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. Study design: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3±0.6 mmol/l to 24.4±1.2 mmol/l (P<0.0001) and 7.34±0.03 to 7.40±0.02 (P<0.0001). Serum albumin increased from 34.9±2.1 g/l to 37.9±2.9 g/l (P<0.01) while PCRn decreased from 1.11±0.17 g/kg/day to 1.03±0.17 g/kg/day (P<0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. Conclusions: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentration in HD patients. The correction of acidosis induced a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.     

Stimulation of tubular secretion of creatinine in health and in conditions associated with reduced nephron mass. Evidence for a tubular functional reserve

Background: The increment in glomerular filtration rate (GFR) after a protein load has been taken to reflect the renal reserve capacity; however, this response is preserved in end-stage kidney disease. Tubular secretion of creatinine is increased in relation to the GFR in renal failure, but little is known about the tubular functional response to stimulation despite the fact that tubulointerstitial lesions are always pre-eminent in chronic renal damage. Therefore we decided to compare the urinary creatinine excretion (UcrV) and tubular secretion of creatinine (TScr) induced by a test meat meal in normal individuals and in individuals with reduced nephron mass. Methods: We studied 12 normal subjects, seven healthy uninephrectomized (kidney donors) and eight patients with chronic renal disease (serum creatinine ranging from 121.2 to 486 &mgr;mol/l). They had been on a standard diet for 5 days before the studies. The test meal provided 80 g of animal protein. Three baseline and four stimulated (post-meal) 30-min simultaneous inulin and creatinine clearances were carried out. Results: We found that normals increased more than twice the UCrV (post-meal=329.5±SEM 13.1 nmol/min/kg) and 3.4 times the TSCr (114,4±12.7 nmol/min/kg) after the test meal. In contrast, patients were unable to raise their baseline values (P<0.001), despite a normal increment in GFR. The data in kidney donors fell between normals and patients. Strong correlation existed between the stimulated (but not the baseline) TScr (P=0.003) and GFR and between UcrV post-meal/pre-meal ratio and GFR (P<0.0001). Conclusion: The increment in TScr resulting from a protein meal is related to the functioning nephron mass. Evaluation of this increment could have potential clinical relevance.     

Urinary Excretion of Pyridinium Cross-Links and Serum Osteocalcin Levels in Patients with Primary High-Grade Osteosarcoma

Osteosarcoma is the most frequent primary high grade bone tumor, usually occurring in adolescents and children. The aim of the present study was to investigate parameters of bone turnover as urinary excretion of pyridinoline (Pyr), and deoxypyridinoline (D-Pyr), serum osteocalcin (OC), and total alkaline phosphatase (AP) in patients with osteosarcoma. Thirty-five patients aged 7–22 (median age 14) with primary high-grade osteosarcoma of the extremity entered the study. A control population of age- and sex-matched healthy individuals was studied. Urinary excretion of Pyr, D-Pyr was measured on fasting urine specimens, corrected for creatine excretion (Ucr), and expressed as pM/µM UCr. At the same time as urine collection, blood samples were taken for measurement of AP and OC. In patients with osteosarcoma the urinary excretion of D-Pyr (74.5 ± 41) was significantly higher (P = 0.005) than in controls (38.2 ± 22.5). The serum level of OC was significantly lower (P < 0.001) in patients with osteosarcoma than in controls. Moreover, significantly (P = 0.03) higher excretion of D-Pyr (85.3 ± 43) was found in patients who relapsed after surgical removal of the tumor and chemotherapeutic treatment compared with those (58.1 ± 22) who remained continuously free of disease. The present study showed significant abnormalities of urinary excretion of pyridinium crosslinks and serum OC level in patients with osteosarcoma. The relation between urinary excretion of D-Pyr and biological tumor aggressiveness observed in the present study requires further investigation.     

Urinary calcium excretion in healthy Thai children

The objective of this study was to determine age-specific reference values for urinary calcium/creatinine ratios (UCa/Cr) of children in southern Thailand. Non-fasting urine samples were collected from a random population of 488 healthy children (282 males, 206 females) ranging in age from 17 days to 15 years. Samples were divided into six groups by age. Subjects whose calcium levels exceeded the 95th percentile within each age group were classified as having hypercalciuria. Pyuria, hematuria, proteinuria, urinary sodium, and potassium levels in children with normal UCa/Cr were compared with levels in children with high UCa/Cr. The 95th percentiles for UCa/Cr (mg/mg) by age were: <6 months, 0.75; 6 months to <12 months, 0.64; 12 months to <2 years, 0.40; 2 years to <5 years, 0.38; 5 years to <10 years, 0.29; and 10 years to <15 years, 0.26. Pyuria, hematuria, and proteinuria were no more prevalent in the 22 children with hypercalciuria than in children with normal urinary calcium levels. Urinary sodium/creatinine ratios (UNa/Cr) and urinary sodium/potassium ratios (UNa/K) were correlated with UCa/Cr (r=0.41, P<0.0001 and r=0.24, P<0.0001, respectively). Urinary potassium/creatinine ratios (UK/Cr) were not (r=0.05, P>0.1)). Children with high UCa/Cr ratios also had higher UNa/Cr and UNa/K (5.6±7.1 vs. 2.6±1.5, P<0.001 and 5.4±2.3 vs. 2.5±0.23, P<0.05, respectively) The study established reference values for random, non-fasting UCa/Cr for healthy Thai children and indicated that urinalysis is not a good indicator of hypercalciuria. Received: 30 April 1999 / Revised: 19 August 1999 / Accepted: 19 August 1999