Optimising nutrition in chronic renal insufficiency—progression of disease

There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n =19) CRI. Children with CRI were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were –9.4, –5.8, and –6.0 ml/min per 1.73 m² for mild, moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes, median sodium intakes increased (+10 mmol/day) and protein intakes decreased (–0.4 g/kg per day). Median phosphate intakes did not change significantly, whereas calcium intakes fell in all groups, with an overall median of –20% reference nutrient intake (RNI) (F =33.3, P <0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F =6.0, P =0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r ²=0.30, P =0.02; r ²=0.31, P =0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression.     

Optimising nutrition in chronic renal insufficiency—growth

The need to optimise nutrition to promote growth in infants with chronic renal insufficiency (CRI) is well recognised, but there is less enthusiasm for such an approach in older children and those with milder degrees of CRI. Energy intakes and growth outcomes were prospectively monitored over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/ dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n=19) CRI. Children were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI), and were excluded if they required dialysis. None received growth hormone. Regular dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly anthropometric measurements were obtained. Mean height standard deviation score (SDS) was maintained in those with mild and moderate CRI and significantly increased in children with severe CRI [0.1 SDS (0.32 SD), F =9.45, 1 df, P =0.003]. There was a non-significant reduction in energy intake from dietary records overall (median –8.5% estimated average requirement), associated with poor adherence to supplements in severe CRI and under-reporting in the mild group. An increase in height or body mass index SDS, however, was observed in all children who took the supplements as prescribed. A correlation between change in energy intake and change in height SDS was observed in severe CRI ( r ²=0.58, P =0.011). Regular dietetic advice, with particular attention to adherence to optimise energy intake, may improve growth, irrespective of age and should form an integral part of the clinical care package.     

Predictive factors of chronic kidney disease in severe vesicoureteral reflux

The aim of this retrospective cohort study was to evaluate independent predictive factors of chronic kidney disease (CKD) in children with severe bilateral primary vesicoureteral reflux (VUR). Between 1970 and 2004, 184 patients were diagnosed with VUR (grades III–V) and were systematically followed up at a single tertiary renal unit. CKD was defined as estimated glomerular filtration rate <75 ml/min per 1.73 m² body surface area in two consecutive examinations. Risk of CKD was analyzed by the Kaplan–Meier method and Cox’s regression model. The probability of CKD for patients with bilateral severe reflux was estimated at 15% by 10 years after VUR diagnosis. After adjustment, four variables remained independently associated with CKD during follow-up: age at diagnosis >24 months [relative risk (RR)=4.8, 95% confidence interval (95%CI), 1.8–12.7, P<0.001], VUR grade V (RR=3.5, 95%CI, 1.5–7.9, P=0.002), bilateral renal damage (RR=2.86, 95%CI, 1.3–6.1, P=0.007), and decade of admission after 1990 as a protective factor (RR=0.16, 95%CI 0.06–0.43, P<0.001). A delay in the diagnosis of VUR more than 12 months after urinary tract infection (UTI) was also a predictive factor in an alternative model (RR=2.2, 95%CI, 1.1–6.6, P=0.03). Prognosis regarding renal function was relatively poor after a long-term follow-up of patients with bilateral severe reflux.     

Gender and vesico-ureteral reflux: a multivariate analysis

The aim of this retrospective cohort study was to describe the characteristics of patients with primary vesico-ureteral reflux (VUR) with special attention to gender-specific differences. Between 1970 and 2004, 735 patients were diagnosed with VUR and were systematically followed in a single tertiary renal unit. The following variables were analyzed: race, age at diagnosis, clinical presentation, weight and height Z-score, unilateral/bilateral reflux, VUR grade, renal damage, severity of renal damage, constipation, and dysfunctional voiding. Comparison of proportion between genders was assessed by the chi-square test with Yates’ correction. The logistic regression model was applied to identify independent variables associated with gender. A survival analysis was performed to evaluate VUR resolution. After adjustment, five variables remained independently associated with male gender at baseline: non-white race [Odds ratio (OR) = 1.98, 95% confidence interval (95% CI) 1.33–2.95, P=0.001], moderate/severe grade of reflux (OR=2.16, 95% CI 1.45–3.22, P<0.001), severe renal damage (OR=1.60, 95% CI 1.04–2.52, P=0.04), age at diagnosis <24 months (OR=1.79, 95% CI 1.23–2.60, P=0.002), and antenatal clinical presentation (OR=3.56, 95% CI 1.91–6.63, P<0.001). Follow-up data were available for 684 patients (93%). Median follow-up time was 69 months (range 6 months to 411 months). Girls had a greater risk of urinary tract infection (UTI) during follow-up than boys (OR=1.68, 95% CI 1.18–2.38, P=0.003). There was no difference in progression to chronic renal insufficiency (CRI) between boys (3.8%) and girls (2.4%) during this period of follow-up (OR=1.58, 95% CI 0.59–4.15, P=0.44). Gender as an isolated variable is a poor predictor of clinical outcome in an unselected series of primary reflux. Although boys had a more severe pattern at baseline, girls had a greater risk of dysfunctional voiding and recurrent UTI during follow-up.     

Serum cystatin C and left ventricular diastolic dysfunction in children with chronic kidney disease

Previous studies indicate that serum cystatin C predicts incident heart failure in older adults. Children with chronic kidney disease (CKD) develop left ventricular (LV) diastolic dysfunction, often the initial abnormality of cardiac function. We hypothesized that cystatin C might predict LV diastolic dysfunction in children with CKD. Fifty-seven subjects, aged 6–21 years, with stage 2–4 CKD underwent echocardiography. Diastole was assessed from transmitral Doppler [maximum early (E wave) and late (A wave) diastolic flow velocities (E/A ratio)] and from tissue Doppler [septal mitral annular peak velocities (E′)]. LV filling pressures were determined, using a ratio of E/E′. Fourteen (25%) patients had low E′ and 15 (26%) had high E/E′. Children with abnormal E′ or E/E′ had significantly higher cystatin C levels than children with normal indices (P<0.05). Neither serum creatinine nor measured glomerular filtration rate (GFR) significantly correlated with E’ or E/E’. Stepwise multiple regression analysis showed that cystatin C (β=−0.825, P=0.023) and left ventricular mass (LVM) index (β=0.099, P=0.006) independently predicted E′; LVM index independently predicted E/E′ (β=0.0173, P=0.01). We conclude that, in contrast to measured GFR or serum creatinine level, elevated serum cystatin C might be associated with diastolic dysfunction in children with CKD.     

Impact of ACE I/D gene polymorphism on congenital renal malformations

To investigate the role of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on prevalence and progression of disease in children with chronic renal failure (CRF), we determined the ACE I/D genotype in 95 children with CRF due to renal malformations (hypo- /dysplasia, obstructive uropathy, reflux nephropathy; n=59), other congenital or hereditary diseases (n=23), or acquired glomerular disorders (n=13), who had been followed prospectively over a 2-year period. CRF progression rate was followed in each individual by linear regression analysis of estimates of glomerular filtration rate (GFR) obtained every 2 months. Actuarial renal ’survival’ analysis was performed, using a GFR loss of 10 ml/min per 1.73 m² as a cutoff point. The distribution of the ACE genotype did not differ among the disease groups. There was also no difference in ACE genotype distribution between the patients and a control group of healthy Caucasian children (n=163). Among the children with renal malformations, the 2-year renal survival was significantly lower in those with the DD genotype (61%) than in patients with ID or II genotype (89%, P<0.01). In the other disease groups, the ACE I/D genotype was not predictive of CRF progression. In a multivariate analysis of risk factors, the adverse effect of the DD genotype (risk ratio 10.2, P<0.05) was independent of and additive to those of arterial hypertension (RR 13.2, P<0.001) and gross proteinuria (RR 4.7, P<0.05). We conclude that the ACE DD genotype is a significant risk factor for children with congenital renal malformations to develop progressive CRF. The effect of the ACE polymorphism in this patient group is independent of hypertension and proteinuria. Received: 25 August 2000 / Revised: 10 December 2000 / Accepted: 15 December 2000     

Candesartan cilexetil in children with hypertension or proteinuria: preliminary data

The angiotensin II receptor blockers irbesartan and losartan effectively reduce blood pressure and proteinuria in childhood. We were impressed by the neutral taste and the small size of the candesartan cilexetil tablets. This angiotensin II receptor blocker was used during 4 months in 17 pediatric patients (aged 0.5–16, median 4.5 years) with chronic arterial hypertension (n=6), overt proteinuria (n=2), or both (n=9). The initial candesartan dose of 0.23 (0.16–0.28) mg/kg body weight once daily (median and interquartile ranged) was doubled in ten patients [final dose 0.35 (0.22–0.47) mg/kg body weight]. No adverse clinical experiences were noted on candesartan. Candesartan increased plasma potassium by 0.3 (0.0–0.8) mmol/l (P<0.01). In children with arterial hypertension, blood pressure decreased by 9 (3–13)/9 (3–18) mmHg (P<0.01); in those with overt proteinuria the urinary albumin/creatinine ratio decreased by 279 (33–652) mg/mmol (P<0.05). In conclusion, in children candesartan reduces blood pressure and proteinuria with an excellent short-term tolerability profile.     

Growth after renal transplantation in infancy or early childhood

Forty-one children <5 years of age at kidney transplantation (TX) were investigated for growth, bone age, and renal function up to 7 years (n=26) after TX. All children received triple immunosuppression, including alternate-day corticosteroid treatment. Catch-up growth was seen in 81% of 30 children without growth hormone (GH) treatment. Children <2 years of age without GH had a mean height standard deviation score (hSDS) of –1.1±0.8 at TX and –1.1±0.5 at 7 years; children between 2 and 5 years improved their hSDS from –1.9±0.9 to –0.4±0.8 (P<0.0001). The hSDS at TX correlated inversely with the ΔhSDS from TX to 7 years (r=–0.80, P=0.0002). Glomerular filtrations rate (GFR) at 5 years post TX correlated with the subsequent growth rate from 5 to 7 years TX (r=0.58, P=0.01). Catch-up growth was seen in all 11 children receiving GH. Their mean hSDS improved from –2.5±0.9 to –1.1±0.9 (P<0.0001). In the majority of children receiving a kidney graft in early life, triple immunosuppression with alternate-day steroids can ensure catch-up growth. In children <5 years of age at TX, growth is predicted better by the degree of stunting than by age. Received: 9 September 2001 / Revised: 2 January 2002 / Accepted: 4 January 2002     

Long-term follow-up of Czech children with D+ hemolytic-uremic syndrome

Fifty-seven children (f/m=31/26) who survived diarrhea (D) + hemolytic uremic syndrome (HUS) were evaluated. The examinations were performed 1–27 years (median 7 years) from the onset of the acute disease. Patients aged 2.3–27 years (median 10 years) were allocated to three groups: Recovery (R, complete recovery), Residual renal symptoms (RRS, hematuria and/or proteinuria and/or hypertension with glomerular filtration rate (GFR) >80 ml/min/1.73 m², or moderate renal insufficiency with slightly decreased GFR to 60–80 ml/min/1.73 m² with or without residual renal symptoms), and Chronic renal insufficiency/failure (CRI/F, dialysis, transplantation – GFR <60 ml/min/ 1.73 m²). Results from 18 patients who survived more than 10 years after HUS demonstrated a high prevalence of renal damage. Only 6/18 patients were in group R, 7/18 patients were in group RRS and 5/18 patients were in group CRI/F. An early onset of HUS (36 patients between 0 and 2 years) was associated with a better prognosis when compared with late onset (21 patients aged more than 2 years), P=0.009. Serology typing of Human leukocyte antigens (HLA) classes I and II in 64 patients revealed a significantly higher frequency of DR9 antigen (P=0.0037) and a lower frequency of DQ1 antigen (P=0.009) in D+HUS patients compared with healthy Czech blood donors. Conclusion: Our study demonstrates a high prevalence of late renal damage in Czech patients surviving after D+HUS. The HLA typing in our group revealed a significantly higher rate of HLA DR9 haplotypes in D+HUS patients. Received: 4 January 2001 / Revised: 9 October 2001 / Accepted: 2 January 2002     

Effect of malnutrition on serum creatinine and cystatin C levels

The concentration of cystatin C has been shown to be independent of age, gender and height, but the effect of malnutrition has not been studied. Levels of serum creatinine and cystatin C were estimated in 77 malnourished and 77 normally nourished boys between 2 years and 6 years of age without evidence of renal disease. The mean (95% confidence interval) serum creatinine level in the malnourished boys was significantly lower than that in the normally nourished boys [0.42 (0.38–0.45) mg/dl and 0.51 (0.48–0.55)] mg/dl, respectively, (P < 0.01)]. The mean level of serum cystatin C was 1.05 (0.94–1.17) mg/l and 1.12 (1.01–1.24) mg/l, respectively, in normally nourished and malnourished boys (P = 0.35). Mean glomerular filtration rate (GFR) estimated by the Schwartz equation in the malnourished boys was significantly higher than that in normally nourished children [141.8 (123.3–160.2) ml/min per 1.73 m² body surface area and 119.4 (109.3–129.5) ml/min per 1.73 m² body surface area], respectively (P = 0.04). However, the mean cystatin C-derived GFR was similar in the malnourished and normally nourished boys [99.70 (85.8–113.5) ml/min per 1.73 m² and 109.2 (94.4–124.0) ml/min per 1.73 m²], respectively (P = 0.35). The mean bias between GFR estimates using Bland and Altman analysis was greater in the malnourished children than in the normally nourished children (32.3% and 17.6%, respectively) (P = 0.15). Serum creatinine levels are lower in malnourished children and lead to overestimation of GFR, while cystatin C levels are unaffected.     

Sequential analysis of variation in glomerular filtration rate to calculate the haemodynamic response to a meat meal

BACKGROUND: The renal haemodynamic response to a meat meal is usually measuredas either filtration capacity (maximal achieved GFR), or renalreserve (maximal GFR increase over baseline), or percent renalreserve (maximal GFR increase as a percentage of baseline).The time-course of GFR response to a meat meal varies in differentindividuals as the peak GFR tends to occur late in renal disease.This study proposes a new method to measure the GFR responseindependently of differences in peaking time. METHODS: The study is based on measurement of GFR (inulin clearance,ml/minx1.73 m² BSA) in three 30-min pre-meal clearance periods(baseline) followed by analysis of the GFR changes for up to180 min (four 30-min and one 60-min clearance periods) aftera meat meal (2 g of protein/kg of BW as red cooked meat). Datawere analysed from 85 healthy people (GFR100) and 273 individualswith renal disease (RD) who were divided into three groups basedon their baseline GFR (RD1, n=115, GFR 99–66; RD2, n=85,GFR 65–33; RD3, n=73, GFR<33). RESULTS: In healthy people after the meat meal GFR peaked between 30and 60 min and returned to baseline by 120 min. In the threeRD groups GFR peaked later than in healthy people (P<0.001)and remained higher than baseline for up to 180 min (P<0.001).Cumulative post-meal GFR changes, calculated as cumulative GFRincrease over baseline up to 120 min after meal (ml/120minx1.73m²BSA), were significantly different (P<0.01) in the four groups(healthy people, 937±141; RD1, 1222±141; RD2,587±104; RD3, 361±89). Interindividual variabilityin cumulative GFR increase was only partially explained by thevalue of nitration capacity (r²=0.285), renal reserve (r²=0.640),and percent renal reserve (r₂=0.175). CONCLUSIONS: The data indicate that commonly used parameters are poor indicesof the actual total time-course of the renal response to a proteinload.     

Longitudinal analysis of performance of estimated glomerular filtration rate as renal function declines in chronic kidney disease

Background. Numerous studies have assessed the accuracy of equationsestimating glomerular filtration rate (eGFR) from serum creatininein individuals with chronic kidney disease (CKD) in cross-sectionalstudies. Limited literature exists, however, on the consistencyof performance of these equations in longitudinal studies asrenal function declines. Methods. Radionucleotide-measured GFR from 155 predialysis patientswith stage 3–5 CKD was compared with eGFR derived fromfour equations [6-variable Modification of Diet in Renal Disease(6-MDRD), 4-variable MDRD (4-MDRD), Cockcroft–Gault (CG)and Cockcroft–Gault equations corrected for body surfacearea (CGC)] at baseline, 12 and 24 months. Bias (differencebetween eGFR and measured GFR) was used as a measure of performance.Restricted Maximum Likelihood (REML) models were used to identifyvariables potentially affecting the performance of estimatingequations across time. Results. Mean measured GFR (±SD) at baseline, 12 and24 months was 25.9 ± 10.7, 23.1 ± 10.6 and 20.3± 10.1 mL/min/1.73 m², respectively. There was a statisticallysignificant negative association between bias and GFR for allfour estimates (range: –0.76 to –0.71, P < 0.001for all), indicating worsening underestimation and overestimationat higher and lower GFR, respectively. This negative associationsignificantly reduced over the 24 months (P < 0.001); however,this was largely due to persistent underestimation of eGFR fromindividuals with GFR >50 mL/min/1.73 m². For those with abaseline GFR <50 mL/min/1.73 m², the change in bias for anyof the four equations over 24 months was 1.1 mL/min/1.73 m²,suggesting relatively preserved performance with time. The MDRDequations showed a sustained advantage in estimating renal functionthat was more evident as GFR declined. Conclusion. GFR estimates are inexpensive and show an acceptablelongitudinal performance for monitoring CKD patients with GFR<50 mL/min/1.73 m². Inaccuracies appear more substantialabove this level of GFR, and care with interpretation is required.     

Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease

Very few biomarkers exist for monitoring chronic kidney disease (CKD). We have recently shown that serum neutrophil gelatinase-associated lipocalin (NGAL) represents a novel biomarker for early identification of acute kidney injury. In this study, we hypothesized that serum NGAL may also represent a biomarker for the quantitation of CKD. Forty-five children with CKD stages 2–4 were prospectively recruited for measurement of serum NGAL, serum cystatin C, glomerular filtration rate (GFR) by Ioversol clearance, and estimated GFR (eGFR) by Schwartz formula. Serum NGAL significantly correlated with cystatin C (r=0.74, P<0.000). Both NGAL and cystatin C significantly correlated with measured GFR (r=0.62, P<0.000; and r=0.71, P<0.000, respectively) as well as with eGFR (r=0.66, P<0.000 and r=0.59, P<0.000, respectively). At GFR levels of ≥30 ml/min per 1.73 m², serum NGAL, cystatin C, and eGFR were all significantly correlated with measured GFR. However, in subjects with lower GFRs (<30 ml/min per 1.73 m²), serum NGAL levels correlated best with measured GFR (r=0.62), followed by cystatin C (r=0.41). We conclude that (a) both serum NGAL and cystatin C may prove useful in the quantitation of CKD, and (b) by correlation analysis, NGAL outperforms cystatin C and eGFR at lower levels of measured GFR.     

Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate

Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR). In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7–18 years) with various renal pathology referred for ⁵¹Cr-EDTA clearance investigations were obtained for measurement of Cys-C as well as β₂-microglobulin (β2-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m² constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94±0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between ⁵¹Cr-EDTA clearance and the reciprocal of Cys-C (r=0.64, P<0.0001), β₂-MG (r=0.59, P<0.0001), creatinine (r=0.55, P<0.0001), and the height/creatinine ratio (r=0.73, P<0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced GFR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula. We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or β2-MG concentrations. Received: 15 June 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Disparities in Gastric Cancer Outcomes Among Asian Ethnicities in the USA

Background  Survival for gastric cancer is reportedly higher in Asians than for other races. It is unclear whether differences in outcome exist among Asian ethnicities. Our objective was to assess gastric cancer survival in Asian ethnic groups in a large heterogeneous population. Methods  Asian-Americans treated for gastric adenocarcinoma between 1988 and 2006 were identified from the Los Angeles County Cancer Surveillance Program. Patients were stratified and compared by ethnicity (Korean, Japanese, Chinese, Vietnamese or Filipino). Results  Of the 1,817 Asian-Americans in the study cohort, 45% (n = 810) were Korean, 25% (n = 462) were Chinese, 11% (n = 193) were Japanese, 10% (n = 188) were Filipino, and 9% (n = 164) were Vietnamese. For the entire cohort Koreans and Filipinos had the longest and shortest median survival (MS), respectively (22.4 and 10.3 months, respectively; P < 0.001). Multivariate analysis demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.08–1.73, P = 0.008; and HR 1.71, 95% CI 1.37–2.13, P < 0.001, respectively]. In the surgical cohort, Koreans and Filipinos had the longest and shortest survival, respectively (MS of 57.8 and 21.7 months, respectively; P < 0.001). Multivariate analysis of the surgical cohort also demonstrated that Japanese and Filipino ethnicity independently predicted worse survival compared with Korean ethnicity (HR 1.61, 95% CI 1.22–2.13, P < 0.001; and HR 1.66, 95% CI 1.24–2.22, P < 0.001, respectively). Conclusion  There are differences in gastric cancer survival among Asian ethnicities. Future studies addressing varying environmental exposures and molecular expression patterns in gastric cancer are warranted to better understand these disparities in outcome. This study was presented at the Society of Surgical Oncology’s 62nd Annual Cancer Symposium on March 7, 2009.     

Long-term enteral nutrition in infants and young children with chronic renal failure

An inadequate nutritional intake is common in infants and young children with chronic and end-stage renal failure (CRF/ESRF), causing poor weight gain and growth retardation. In a programme of enteral feeding (EF), growth, nutritional intake and outcome for oral feeding were evaluated in 35 children with CRF/ESRF, mean (range) age 1.6 (0–4.9) years at start of EF for 30 (12–60) months. Twenty-nine had a glomerular filtration rate of 12.1 (6–26) ml/min per 1.73 m² and 6 were on peritoneal dialysis. Mean (SD) weight standard deviation scores (SDSs) in the 0 to 2-year age group (n=26) were –3.3 (1.0) 6 months before EF, –3.1 (1.3) at the start, –1.7 (1.4) at 1 year, (P=0.0003) and –1.4 (1.8) at 2 years, (P=0.0008). Height SDSs were –2.9 (0.7), –2.9 (1.2), –2.2 (1.2) (P=0.008) and –2.1 (1.3) (P=0.004). Weight SDSs in the 2 to 5-year age group (n=9) were –2.3 (1.2), –2.0 (1.1), –1.1 (1.3) (P=0.002) and –0.9 (1.0) (P=0.04). Height SDSs were –2.8 (0.6), –2.3 (0.7), –2.0 (0.7) and –2.0 (0.8). There was no change in energy intake as a percentage of the estimated average requirement, nor was this exceeded. Percentage energy from the EF in the 0 to 2 year age group remained unchanged despite an absolute increase in energy intake with age. Twenty-one have had renal transplants, of whom 86% eat and drink normally. Long-term EF prevents or reverses weight loss and growth retardation in children with CRF/ESRF, with the achievement of significant catch-up growth if started before age 2 years. Received: 27 July 1998 / Revised: 19 November 1998 / Accepted: 20 November 1998     

Comparison of glomerular function tests in children with cancer

Evaluation of renal function should be performed as part of the follow-up during and after chemotherapy in pediatric cancer patients. The aim of this study was to compare an isotope clearance method [isotope glomerular filtration rate (iGFR)] with alternative methods to determine GFR in such patients. Isotope GFR [^99mTc-labeled diethylene triaminopentoacetic acid (DTPA) or ⁵¹Cr-labeled ethylenediaminetetra-acetate (EDTA)] was measured in 36 children (112 studies) and compared with simultaneously measured creatinine clearance (CrCl), serum creatinine (SCr), and cystatin C (CysC) concentrations, as well as the results of Schwartz, Counahan–Barratt, and Cockroft–Gault formulae, using general linear mixed models. Our results showed a significant association between iGFR and CysC concentrations (p < 0.001). No linear relationship was observed between CrCl and iGFR (p = 0.7). As expected, the results of height-based formulae (Counahan–Barratt and Schwartz) had significantly (p = 0.004) better correlation to iGFR than the results of a formula based on weight (Cockroft–Gault) (p = 0.19). Despite significant linear correlation, intraclass correlation coefficients showed poor agreement. Tests of similarity between iGFR estimates showed differences between average values of GFR. Therefore, determination of iGFR remains the method of choice in estimation of GFR in cancer patients. In our study population, assay of serum CysC was the most reliable alternative method to measure glomerular function.     

Circulating Fibroblast Growth Factor-23 Increases Following Intermittent Parathyroid Hormone (1–34) in Postmenopausal Osteoporosis: Association with Biomarker of Bone Formation

Uncertainties exist regarding whether FGF-23 production is influenced by PTH and its involvement in bone formation. We evaluated FGF-23 response and its relation to changes in biomarkers of bone formation following intermittent PTH treatment. Twenty-seven women with a mean [SD] age of 75.8 [5.4] years with postmenopausal osteoporosis were treated with PTH(1–34) for 18 months. Bone mineral density (BMD) was measured at 6 and 18 months at the lumbar spine (LS) and total hip (TH). Blood samples were obtained at baseline, 1–3, 6–9, and 12–18 months. Serum calcium, phosphate, PTH, 25(OH)vitamin D, 1,25(OH)₂vitamin D, markers of bone turnover, FGF-23, and sclerostin were measured. BMD increased at both the LS (11.6%, P < 0.001) and TH (2.5%, P < 0.01). The bone formation marker P1NP increased early (baseline mean [SD] 39.9 [24.4] μg/l, 1–3 months 88 [37.9] μg/l; P < 0.001) and remained higher than baseline throughout 18 months. FGF-23 also increased, with a peak response at 6–9 months (increase 65%, P = 0.002). Serum phosphate remained stable. A significant increase in 1.25(OH)₂vitamin D (P = 0.02) was seen at 1–3 months only. A small but significant reduction in sclerostin was seen at 6–9 (P = 0.02) and 12–18 months (P = 0.06). There was a positive correlation between changes in P1NP and FGF-23 (6–9 months r = 0.78, P < 0.001). FGF-23 is increased by intermittent PTH(1–34). This is related to early changes in P1NP, suggesting that the skeletal effects of PTH may involve FGF-23. Further studies are required to elucidate this.     

Decreasing glomerular filtration rate - an indicator of more advanced diabetic glomerulopathy in the early course of microalbuminuria in IDDM adolescents?

Background. Overt diabetic nephropathy is accompanied by a progressive decline in glomerular filtration rate (GFR). In this study we have investigated if a reduction of GFR already during the transition from normo- to microalbuminuria is associated with glomerular structural changes. Methods. Seventeen adolescents (11 girls/6 boys) with 10.5 (3.4) (mean, SD) years of IDDM were studied. GFR was previously measured in the normoalbuminuric stage 2-5 years prior to the renal biopsy, and measured again at the time for the biopsy, after in mean 1.8 years of microalbuminuria (15-200 &mgr;g/min). HbAlc and albumin excretion rate were measured 3 or 4 times yearly and blood pressure 1-4 times yearly between the GFR examinations. The associations between the yearly rate of fall in GFR and basement membrane (BM) thickness, mesangial and matrix volume fractions, matrix star volume, mean capillary diameter (CAPD), area of filtration surface (peripheral BM) per glomerulus, total capillary length per glomerulus, the ratio of peripheral BM to capillary surface, glomerular volume, and interstitial volume fraction were analysed. Results. BM thickness and matrix star volume were increased in patients with, as compared to those without, a decline in GFR⩾6 ml/min per year (P<0.005 respectively). Patients with previous glomerular hyperfiltration (⩾135 ml/min per 1.73 m²) showed the steepest decline in GFR; 11 ml/min per year versus -0.8 ml/min per year in previously normofiltering patients, P<0.001. The rate of fall in GFR was positively correlated to BM thickness (P<0.001), interstitial volume fraction (P=0.02) and CAPD (P=0.04), mean HbAlc (P=0.01), but not to the change in HbAlc between GFR examinations. Conclusion. A decreasing glomerular filtration rate in the early stage of microalbuminuria may be due to more advanced diabetic glomerulopathy than in IDDM patients with stable GFR.     

Circulating inflammatory cytokine levels in hemolytic uremic syndrome

Experimental data suggest that the host’s inflammatory response is involved in the pathophysiology of verotoxin-producing Escherichia coli (VTEC)-associated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement for dialysis, and a glomerular filtration rate (GFR) ≤80 ml/min per 1.73 m² measured 1 year later. Increased levels of IL-6 (P<0.0001), IL-10 (P<0.0001), and IL-1Ra (P<0.07) were found among patients with HUS compared with normal controls. Children with severe renal dysfunction also had tenfold increased levels of IL-6 and higher concentrations of IL-10 and IL-1Ra. Both the IL-6/IL-10 (4.9±8.3 vs. 0.5±0.4, P=0.01) and the IL-6/IL-1Ra ratios (0.10±0.20 vs. 0.01±0.01, P=0.04) were significantly increased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra ratios. Our data demonstrate that the inflammatory response of the host is associated with the severity of renal dysfunction during classic HUS. An imbalance between the pro- and the anti-inflammatory responses may be involved in the pathophysiology of VTEC-associated HUS. Received: 3 August 1998 / Revised: 24 November 1998 / Accepted: 25 November 1998