Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9–13.9) years, GFR 19 (9–58) and ERPF 77 (34–271) ml/min per 1.73 m². During treatment height velocity increased from 4.5 (1.7–6.5) to 9.5 (4.8–12.7) cm/year (P<0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6–56) and after 1 year, 20 (9–59) ml/min per 1.73 m². ERPF increased to 96 (33–276) ml/min per 1.73 m² on day 8P=0.005), and remained elevated, but not significantly so, at 99 (24–428) ml/min per 1.73 m² at 1 year. Fasting IGF-I increased from 147 (46–315) ng/ml to 291 (61–673) by day 8P<0.003), and to 341 (101–786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment. The significance of increased ERPF after 1 week of rhGH in CRF is unclear, but long-term follow-up of renal function is indicated.     

Validation of child serum creatinine-based prediction equations for glomerular filtration rate

Equations for estimating glomerular filtration rate (GFR) are vital in caring for patients with renal disease and the current standard, the Schwartz formula, lacks precision. We evaluated several child serum creatinine-based GFR prediction equations. Subjects aged 2–21 years who underwent iothalamate GFR (IoGFR) testing between 1999 and 2004 were studied retrospectively. GFR was estimated using: (1) Schwartz formula (SchwartzGFR), using a local k value; (2) Schwartz model (SchwartzMod) using regression-derived coefficients; (3) Leger GFR (LegerGFR) using original coefficients; and (4) Leger model (LegerMod) using regression-derived coefficients. Bias, precision, and diagnostic characteristics were evaluated. There were 195 subjects [61% male; mean (SD) age 12.4 (4.5) years; mean (SD) IoGFR 78.9 (33.4) ml/min per 1.73 m²]. Only the LegerGFR overestimated IoGFR (5.5 ml/min per 1.73 m²). Precision for all formulae was poor (95% limits of agreement approximately −40 to 40 ml/min per 1.73 m²), but ≥72% of estimates were within 30% of IoGFR. Sensitivities for detecting IoGFR <30 and 90 ml/min per 1.73 m² were highest using the SchwartzGFR (80%) and SchwartzMod (90%), respectively. The LegerGFR was most specific. Using local coefficients, the Schwartz and Leger models were imprecise estimates of GFR, but the Schwartz model was most unbiased and sensitive. Future research should derive more precise equations for GFR in children. The work was performed at McGill University Health Centre, Montreal, Quebec, Canada. There were no direct sources of support for this research. However, a significant portion was performed while Dr. Zappitelli was receiving research fellowship funding by the Kidney Research Scientist Core Education and National Training (KRESCENT) Program (Kidney Foundation of Canada, Canadian Society of Nephrology, and Canadian Institutes of Health Research).     

Etiology of chronic renal failure in Turkish children

The etiology of chronic renal failure (CRF) was studied in 459 Turkish children (205 girls, 254 boys) for the period January 1979-December 1993. Their mean age at onset of CRF was 9.5±4.2 years (range 1–16 years); CRF was defined as a glomerular filtration rate (GFR) below 50 ml/min per 1.73 m² for at least 6 months. When a GFR determination was not available, the serum creatinine concentration was used: greater than 1 mg/dl for children aged 1–3 years, greater than 1.5 mg/dl for those 3–10 years and greater than 2 mg/dl for those 10–16 years. Primary renal disorders were as follows: reflux nephropathy 32.4% glomerular diseases 22.2%, hereditary renal disorders 11.4%, amyloidosis 10.6%, urinary stones 8% and other renal disorders 15.4%. Twenty-three cases of reflux nephropathy (15.4%) were associated with neural tube defects (NTD) and 20 (13.4%) were caused by infravesical obstruction. CRF caused vesicoureteral reflux associated with NTD and amyloidosis are more frequent in our series compared with west European and Nordic countries.     

Validation of the Center for Medicare and Medicaid Services algorithm for eligibility for dialysis

The Center for Medicaid and Medicare Services (CMS) has recently revised their end-stage renal disease (ESRD) Medical Evidence Report, Medicare Entitlement, and Patient Registration CMS 2728 Form. The modified algorithm calls for the use of formulae to estimate glomerular filtration rate (GFR). The new criterion is defined as estimated GFR of less than 20 ml/min per 1.73 m². GFR is either estimated by Schwartz formula (C_SCH) in children or Modification of Diet in Renal Disease formula (C_MDRD) in adults. The purpose of this communication is to test the validity of the new CMS GFR algorithm in detecting children who need renal replacement therapy. We evaluated two cohorts of children. Group I included single-center data from 626 ¹²⁵I-iothalamate clearance studies (C_IO) that were compared with the simultaneous estimation of GFR by C_SCH. Group II included data on 659 children from the patient incidence registry obtained from the ESRD Network of Texas between February 1996 and October 2003. In group I there were 76 children (76 C_IO) with C_SCH less than 20 ml/min per 1.73 m² of whom 50 (67%) had C_IO less than 15 ml/min per 1.73 m². Of children with C_IO less than 15 ml/min per 1.73 m², 62% had a C_SCH less than 20 ml/min per 1.73 m². The ability of C_SCH greater than 20 ml/min per 1.73m² to predict C_IO greater than 15 ml/min per 1.73 m² (negative predictive value) is 0.95. The number of children who were started on dialysis in Texas within the study period was 659 (group II). The mean C_SCH±SD was 10.8±7.7 ml/min per 1.73 m². Of the patients who were initiated on dialysis, 94% had C_SCH less than 20 ml/min per 1.73 m². The results were sustained when race, gender, age range, and type of diagnosis were considered. The new CMS algorithm provides a good negative predictive estimate of GFR less than 15 ml/min per 1.73 m². Disclaimer The analyses upon which this publication is based were performed under contract number 500–03-NW14 entitled End-Stage Renal Disease Networks Organization for the State Texas, sponsored by the Centers for Medicare and Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Centers for Medicare and Medicaid Services, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed.     

Neuropathic bladder as a cause of chronic renal failure in children in developing countries

Neuropathic bladder is considered a threat to the kidneys if not managed appropriately. In this study, we report our experience with neuropathic bladder at King Abdulaziz University Hospital (KAUH) as a cause of chronic renal failure (CRF) in the pediatric age group. This retrospective study included all children diagnosed with neuropathic bladder who presented with moderate or severe CRF over a 4-year period from December 2000 to December 2004 [glomerular filtration rate (GFR) at presentation <50 ml/min per 1.73 m²]. Fifteen patients were diagnosed with neuropathic bladder; group A consisted of ten patients with spina bifida and one with sacral agenesis and group B consisted of four patients with nonneurogenic neurogenic bladders (NNNB). The mean age±SD at presentation was 6.2±3.8 years, GFR was 24.2±12.4 ml/min per 1.73 m², and creatinine was 289.9±253.2 μmol/l. There were no differences in the age at presentation to a pediatric nephrologist or the degree of renal failure at presentation between the two groups. Clean intermittent catheterization (CIC) was not started in all patients before presentation to KAUH, except in two children. Five children required dialysis as they were in end-stage renal failure (ESRF). All except one received peritoneal dialysis (PD). Their mean age at the start of dialysis was 10.8±1.7 years. Neuropathic bladder due to spina bifida or NNNB is an important cause of CRF in developing countries. There was a considerable delay in the diagnosis of NNNB and a significant delay in starting CIC in all neuropathic patients.     

Limitations to body length/serum creatinine ratio as an estimate of glomerular filtration in children

The ability of the Schwartz formula (C _SCH) to estimate glomerular filtration rate (GFR) accurately was investigated in children with renal disease. ¹²⁵Iodine-iothalamate clearance (C _IO) was used as the reference standard for measuring GFR. Data from 176 C _IO studies performed on 133 children (aged between 1 and 18 years) were compared with the simultaneous estimation of GFR by C _SCH. The overestimation of GFR by C _SCH was inversely proportional to the level of renal function. When C _IO was >90 ml/min per 1.73 m², C _SCH overestimated GFR by only 0.1%±3%, but when C _IO was ≤15 ml/min per 1.73 m², C _SCH overestimated GFR by 164%±42%. When renal function is normal or mildly reduced (GFR >50 ml/min per 1.73 m²), C _SCH overestimated C _IO by only 10.3±3.0%, compared with 90.3±14.5% when renal function was moderately to severely curtailed (GFR ≤50 ml/min per 1.73 m²). We conclude that C _SCH is valid in predicting GFR only in children with normal renal function and mild insufficiency. Received January 30, 1996; received in revised form and accepted May 14, 1996     

Renal function during and after childhood acute poststreptococcal glomerulonephritis

It is still debatable whether acute poststreptococcal glomerulonephritis (APSGN) can lead to permanent renal impairment. The clinical, immunological, and histological findings during the acute disease have been described thoroughly, however, the hemodynamic events are still poorly understood. In this retrospective study, the inulin and p-aminohippurate clearances were measured to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) within a month of onset of the disease (acute stage) in 26 children, and 2–12 months after onset (follow-up) in 22 children with APSGN. During the acute stage, the mean GFR was 77±23 (SD) ml/min per 1.73 m², the mean ERPF 537±138 ml/min per 1.73 m², and the filtration fraction (FF) 14%±3%, compared with values for controls of 115±11 ml/min per 1.73 m², 607±72 ml/min per 1.73 m², and 19%±2%, respectively (n=42). At follow-up, GFR was 114±15 ml/min per 1.73 m², ERPF 600±68 ml/min per 1.73 m², and FF 19%±3%. Thus, during the disease both GFR and ERPF fell below values for controls, but later were restored. The GFR, however, was more reduced than the ERPF, as indicated by the reduced FF. This might reflect a relative hyperperfusion of individual nephrons, which might start processes later deleterious to the nephrons. This finding, however, needs to be further investigated and we have therefore started a long-term follow-up of these patients. Received: 24 June 1998 / Revised: 4 December 1998 / Accepted: 7 December 1998     

Validation of the revised Schwartz estimating equation in a predominantly non-CKD population

Recently, Schwartz et al. (J Am Soc Nephrol 20:629–637, 2009) used data from the National Institutes of Health-funded Chronic Kidney Disease in Children (CKiD) study to generate new equations for estimating the glomerular filtration rate (eGFR), including an update of the commonly used bedside equation. However, it is unclear if the equation can be generalized to a broader pediatric population. We have used the updated equation on a sample of pediatric patients with less impaired renal function to evaluate the correlation between the new Schwartz equation and measured GFR by iothalamate clearance. We retrospectively analyzed 738 iothalamate clearance tests from 503 patients with a mean serum creatinine of 0.50 mg/dl whose ages ranged from 1 to 16 years. We measured bias, precision, and accuracy and performed a Bland–Altman plot to determine the measure of agreement between the two methods. The mean GFR by iothalamate clearance was 110.6 ml/min/1.73 m² and by the new Schwartz estimation 104.7 ml/min/1.73 m². The mean difference was 5.84 ml/min/1.73 m² (95% CI 4.00–7.67). The newly purposed bedside Schwartz equation therefore demonstrated good agreement with the iothalamate renal clearances in our patient population and appears to be a valid bedside estimating equation for GFR in this sample of children.     

Independent risk factors and natural history of renal dysfunction in liver transplant recipients

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m² from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m² for at least 6 months) were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m² /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m² were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m² from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m² occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients. (Liver Transpl 2003;9:741-747.)     

Hyperuricemia and gout following pediatric renal transplantation

Hyperuricemia and gout are common complications in adult renal transplant recipients. In pediatric recipients, however, hyperuricemia seems to be rare, but data are scarce. Thirty-two children (21 males, 11 females) were investigated for a median time of 4.8 years (range: 0.4–11.2 years) following renal transplantation. The median age of this pediatric study group was 13.9 years (range: 5.7–20.3 years), and the calculated glomerular filtration rate (GFR) was 61 ml/min per 1.73 m² (range:12–88 ml/min per 1.73 m²). All patients were given calcineurin inhibitors, with 22 and ten children receiving cyclosporine A (CSA) and tacrolimus (TAC), respectively. The median plasma uric acid was 385 μmol/l (range: 62–929 μmol/l); 15 children (47%) were above the age-related normal range. Only one patient experienced gouty arthritis. There was a significant correlation between plasma uric acid concentration and both time span after transplantation and plasma creatinine, and an inverse correlation to GFR (p<0.05). No significant correlation was found between plasma uric acid and body mass index (BMI). Plasma uric acid concentrations were neither different among CSA- and TAC-treated children, nor did they correlate with drug exposure or blood trough levels of CSA or TAC. Plasma uric acid concentration was not different when compared to children with chronic renal failure (CRF) of a similar degree in native kidneys. We conclude that hyperuricemia is common among pediatric renal transplant recipients and rather a consequence of chronic renal transplant dysfunction than the use of calcineurin inhibitors. Gout, however, is rare.     

Deferasirox-induced renal impairment in children: an increasing concern for pediatricians

Background

Deferasirox (DFX) is an oral iron chelator with an established dose-dependent efficacy in transfusion-related iron overload. Whereas emerging long-term data confirm the safety of the drug, with transient moderate elevation of serum creatinine level, several authors have reported renal tubular dysfunction. The aim of this study was to evaluate tubular and glomerular function before and after the initiation of DFX therapy in a pediatric patient population.

Methods

Ten children (4 girls, mean age 12.4?±?3.9?years) enrolled in a routine blood transfusion program were treated with 24.8?±?9.6?mg/kg per day of DFX, and renal function was assessed before and 17.2?±?8.9?months after the initiation of DFX therapy.

Results

Prior to treatment with DFX, all patients had a normal glomerular function rate (GFR) (125?±?15?ml/min per 1.73?m²) and normal tubular function. Following the initiation of DFX therapy, the GFR decreased by approximately 20?% with one patient with a GFR of?<80?mL/min per 1.73?m² and seven patients with a GFR of?<100?mL/min per 1.73?m². Two patients experienced a generalized proximal tubular dysfunction whereas nine patients presented at least one sign of proximal tubular dysfunction.

Conclusions

Renal toxicity is a frequent adverse event of DFX treatment, presenting as both glomerular and proximal dysfunction. A routine renal assessment is therefore required to prevent chronic kidney disease that may result from prolonged tubular injury.     

Prophylactic oral ganciclovir after renal transplantation-dosing and pharmacokinetics

Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered at a starting dose of 3 × 1 g for children with a weight above 50 kg, 3 × 750 mg for children between 50 and 37.5 kg, and 3 × 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values ≤50 ml/min per 1.73 m² and by 75% for GFR values ≤25 ml/min per 1.73 m². The daily dose was divided into three daily doses unless GFR was <40 ml/min per 1.73 m², when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: c _ganciclovir(measured)/c _ganciclovir(desired) = dosage rate(used)/dosage rate(adjusted). Mean stable plasma trough concentration was 0.91±0.68 μg/ml. The dosage rate, adjusted to a trough concentration of 1.0 μg/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR <100 ml/min per 1.73 m²: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects. Received March 3, 1997; received in revised form July 25, 1997; accepted July 30, 1997     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7 – 16) years in 46 patients [median age 11.8 years (range) 3 – 16.8 years]. The median age of the adult donors was 34.4 (19 – 54) years in 59 patients [median age 12.1 years (range) 7 – 17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of ⁵¹chromium-EDTA and ¹²⁵iodine-hippurate 1 – 48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2 – 3 months after transplantation the GFR in recipients of pediatric grafts was 62±20 ml/min per 1.73 m² compared with 61±21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486±239 versus 362±158 ml/min per 1.73 m². From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279±131 ml/min per 1.73 m² compared with 273±123 ml/min per 1.73 m² in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2 – 3 months after transplant the mean GFR of grafts from pediatric donors increased to 118%±51%, whereas the GFR of adult donor grafts fell to 60%±22% over the same period. After 4 – 6 months the ERPF in pediatric grafts was 96%±55% compared with 50%±22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient. Received December 6 1995; received in revised form March 19 1996; accepted March 22 1996     

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3±5.8 (range 3.1–82.6) months after transplantation. Patients were followed up for a mean of 13.2±2.9 (range 1.2–51.1) months. The mean initial MMF dose was 660±56 mg/m² per day, increased to 1,042±73 mg/m² per day a year later. Cyclosporin was reduced from 138±10 mg/m² per day at MMF introduction, to 116±15 mg/m² per day at 6 months and 107±24 mg/m² per day at 1 year. Six months prior to MMF introduction GFR deteriorated by –32.7±7.3 ml/min per 1.73m² per year. Six months after the introduction of MMF, GFR improved by +26.2±7.1 ml/min per 1.73m² per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.Preliminary results of this study were presented at the 7th Annual Congress of the British Transplantation Society, 2004, Birmingham, UK, and at the 13th Congress of the Internal Pediatric Nephrology Association, 2004, Adelaide, Australia     

Glomerular filtration rate is related to severity of obstructive coronary artery disease in patients undergoing coronary angiography

Purpose

Chronic kidney disease is independently associated with an increased risk of cardiovascular events; however, the relationship between the glomerular filtration rate (GFR) and coronary artery disease (CAD) in patients undergoing coronary angiography has yet to be fully elucidated.

Methods

This retrospective study enrolled a total of 7968 patients who underwent diagnostic coronary artery catheterization [mean age?=?54.8?±?10.6?years, 74.4% males] and did not have any previous history of coronary revascularization, diabetes mellitus, hypertension, end-stage renal disease treated by dialysis or renal transplantation, and were not taking diuretics or drugs acting on renin angiotensin system. The severity of CAD was defined as the number of coronary arteries with a luminal stenosis ??50% on the angiogram, and the GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Results

There were 2133 (26.8%) patients with GFR????90?ml/min/1.73?m², 4574 (57.4%) patients with 60????GFR?2, 1073 (13.5%) with 45????GFR?2 and 181 (2.3%) with 15?2. After adjustment for traditional cardiovascular risk factors (age, sex, dyslipidemia, low to high-density lipoprotein ratio, smoking status, and family history), the GFR showed a significant association with the severity of CAD and remained a significant predictor of CAD (Odds Ratio raised from 1.1 in patients with 60????GFR?2 to 1.8 in patients with 15?2).

Conclusions

A reduced kidney function, even mildly, is significantly associated with CAD severity, independently of other traditional CAD risk factors.     

Progression of chronic renal failure in children with dysplastic kidneys

The aim of this study is to describe progression of chronic renal failure (CRF) in children with renal malformations and to study factors influencing this progression. We reviewed retrospectively 176 children with CRF secondary to renal dysplasia, reflux nephropathy or renal obstruction with at least 5 years of follow-up. Serum creatinine was recorded at least every third month, and an estimated glomerular filtration rate (eGFR) was calculated. Number of febrile urinary tract infections (UTI), blood pressure, albuminuria (UaUc), and number of functioning kidneys was also recorded. We found that the development of renal function could be separated into three time periods: (1) During the first years of life, 82% of the children showed early improvement of their kidney function, which lasted until a median age of 3.2 years (median improvement 6.3 ml/year). (2) From the age of 3.2 years until 11.4 years, 52.5% of the studied children showed a stable kidney function, whereas in 47.5%, kidney function immediately started to deteriorate. (3) Around puberty, 42.9% started deterioration in kidney function, whereas 57.1% even after puberty showed a stable function. Patients with UaUc >200 mg/mmol deteriorated faster (−6.5 ml/min per 1.73 m² per year compared with −1.5 ml/min per 1.73 m² per year) in those with UaUc <50 mg/mmol. Children with more than two febrile UTIs, hypertension or an eGFR at onset of less than 40 ml/min per 1.73 m² deteriorated faster than the others. Most children experienced early improvement of kidney function. The further prognosis, early or late deterioration of kidney function or stable function during the whole follow-up, was related to albuminuria, number of febrile UTIs, eGFR at onset of deterioration, hypertension and puberty.     

The renal hemodynamic response following a meat meal in children with chronic renal failure and in healthy controls

The renal hemodynamic response to a meat meal (2 g/kg BW) was studied in 11 healthy children and in 10 children with a mean plasma creatinine concentration of 2.6 +/- 0.1 mg/dl due to chronic renal failure (CRF) of various etiologies. In the healthy status, after a meat meal, the glomerular filtration rate (GFR) increased significantly from a baseline value of 119.0 +/- 5.0 to a peak of 159 +/- 5.8 ml/min x 1.73 m2; in CRF baseline GFR averaged 49 +/- 4.0 and at peak 76.6 +/- 7.2 ml/min x 1.73 m2 (p less than 0.005). The peak GFR response was reached earlier in healthy subjects than in CRF (p less than 0.05) and did not correlate with age or with baseline GFR. Renal plasma flow (RPF) in healthy controls increased from 532 +/- 32 at baseline to 646 +/- 42.9 ml/min x 1.73 m2 after the meal (p less than 0.005). Also in CRF after a meat meal there was a significant increase in RPF from 278 +/- 51 to 65 +/- 66 ml/min x 1.73 m2 (p less than 0.005). The filtration fraction was not affected. The percent increase over baseline values of GFR and RPF at the peak was significantly higher in diseased children. Renal reserve averaged 28.1 +/- 5.3 ml/min in diseased children and 39.7 +/- 5.2 ml/min (p less than 0.01). The data indicate that (1) a meat meal is a suitable method to recruit renal reserve in normal children and in children with chronic renal failure, and (2) the renal reserve is normal in chronic renal failure.     

Decline in Renal Function Following Thoracic Organ Transplantation in Children

Heart and/or lung transplantation are life-saving treatments for end-stage cardiopulmonary disease; however, chronic renal failure may develop. The impact of thoracic organ transplant on renal function in infants and children is not well characterized. This retrospective cohort study evaluated renal function following thoracic organ transplantation in 46 children (32 heart, 9 lung, 5 heart-lung; median age 4.1 years) with at least 12 months of follow-up. Glomerular filtration rate (GFR, ml/min/1.73 m2) was estimated by the Schwartz formula throughout and each GFR estimate was converted to per cent normal for age (GFR%). Changes in renal function following transplantation were analyzed using longitudinal mixed-effects linear regression models. GFR% decreased following thoracic organ transplantation (p <0.001). Younger age at transplant was associated with a greater decline in GFR% (p <0.01). The decline in GFR% persisted after adjustment for nutritional status with body mass index or weight-for-length z-scores. The prevalence of renal insufficiency (GFR% <75) increased from 22% at transplant to 55% and 85% at 1 and 5 years post transplant, respectively, while 15% had a GFR% <50 at 5 years post transplantation. Higher tacrolimus trough levels over the first 6 months correlated with a lower GFR% (p <0.01). Renal function declined significantly following thoracic organ transplantation.     

Anaphylactoid purpura: Characteristics of 16 patients who progressed to renal failure

Renal insufficiency occurs in at least 1.5% of children with anaphylactoid purpura (AP). We reviewed the records of 16 children who developed end-stage renal disease (ESRD group) secondary to AP and matched them for age, era of onset, renal histology, and clinical severity at onset with 16 children who has AP but whose creatinine clearance returned to and remained normal (recovery group). We reviewed creatinine clearances at 1, 3, 5, and 10 years after onset. A creatinine clearance >70 ml/min per 1.73 m² was present in 50% of the patients in the ESRD group at 3 years and in 25% at 5 years after onset. In contrast, all patients in the recovery group had a creatinine clearance >70 ml/min per 1.73 m² by 3 years (7 of 16 had a creatinine clearance >125 ml/min per 1.73 m²) and all were normal 95–125 ml/min per 1.73 m²) by 5 years. Thus, the presence of an increased creatinine clearance (>125 ml/min per 1.73 m²) at 3 years predicted recovery, while failure to reach a creatinine clearance of >70 ml/min per 1.73 m² at 3 years predicted progression to ESRD. There was no evidence of recurrent systemic AP or nephritis in the 14 patients who underwent renal allograft transplantation. We conclude that long-term evaluation of patients over many years is required to identify those who will progress to ESRD from AP and that recurrence of AP in the renal transplant is uncommon.