Early prognostic factors of infants with chronic renal failure caused by renal dysplasia

Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m² at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m² at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m² are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m² have a relatively favorable long-term prognosis. Received: 4 October 1999 / Revised: 26 October 2000 / Accepted: 26 October 2000     

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     

Effects of growth hormone on kidney function in pediatric transplant recipients

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6±3.4 years) received rhGH daily (0.04–0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20±8 months) of rhGH treatment. Their mean serum creatinine level was 1.3±0.7 mg/dl 12 months before, and increased to 3.4±4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.06). Their mean calculated glomerular filtration rate was 58±20 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.     

Advantages of cyclosporin A using 2-h levels in pediatric kidney transplantation

Clinical trials in adult liver and heart recipients have shown that management of cyclosporine (CsA) dose with 2-h levels (C2) leads to lower rejection rates and serum creatinine levels compared with C0 monitoring. Therefore, we investigated whether C2 monitoring might also improve late graft survival after kidney transplantation in children. To date, no results in adult renal transplantation and in pediatric transplantation have been published. Forty-nine stable pediatric kidney recipients with a minimum time of 1 year after transplantation (mean=7±5 years) entered the study. None of the patients had experienced an acute rejection up to 6 months before entering the study. CsA dosing was based on C0 monitoring for the first 6 months and then based on C2 monitoring for the following 6 months. C0 and C2 levels were measured at 4-weekly intervals. Percentage decline in glomerular filtration rate (GFR) and mean coefficients of variation of CsA levels (C_var) were calculated and compared during the 6-months periods. At the beginning of the study, the mean calculated GFR was 53±15 ml/min per 1.73 m². During the 6 months of C0 monitoring, the mean GFR decreased to 49±12 m/min per 1.73 m² (P=0.001, paired t-test). Six months after switching to C2 monitoring, the mean GFR remained stable, at 49±15 ml/min per 1.73 m² (P=0.3 paired t-test). The largest increase in GFR (3.9±7.9%) was found in patients with a decrease of their CsA dose of more than 5% under C2 monitoring. C_var was significantly lower under C2 than under C0 monitoring (0.24±0.10 vs. 0.30±0.15, P=0.02, unpaired t-test). We conclude that the switch to C2 monitoring helped to identify patients with CsA overdosing as well as to reduce variation in CsA level, which resulted in a halt in GFR decline.     

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.     

Growth hormone for children with chronic renal failure and on dialysis

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean±SD duration of therapy 3.7±2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24±12 mL min^–1/1.73 m² at the start of rhGH. Their height standard deviation score improved from –2.5±1.4 to –2.1±0.7 at 1 year (P=0.3), –2.0±0.7 at 2 years (P=0.01), and –1.6±0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from –2.7±0.5 to –2.3±0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean±SD age of 12.1±4.0 years. Mean Ht SDS was –1.8±0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.     

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     

Arterial hypertension following renal transplantation in children—a short-term study

Systemic arterial hypertension is a common complication among transplanted patients. The objective of this study was to investigate the risk factors for arterial hypertension after kidney transplantation in children. A retrospective study was carried out of 70 kidney transplants performed on patients under 18 years of age at the Hospital do Rim and Hipertensão, from January 1998 to June 2001. At the end of 6 months post transplant, the patients were classified into either normotensive (n=31) or hypertensive (n=39) groups. The following potential risk factors for arterial hypertension were studied: (1) hypertension before transplantation; (2) the glomerular filtration rate (GFR) at 1, 3, and 6 months post transplant; (3) acute rejection episodes; (4) cumulative dose of corticosteroids; (5) the presence of native kidneys; (6) symptomatic renal artery stenosis; (7) cold ischemia time greater than 24 h; (8) age and sex of the donor; (9) age of the recipient; (10) transplant type (living related or cadaveric donor); (11) the body mass index of recipients at the end of the follow-up period; and (12) delayed graft function. The two groups were comparable in terms of the etiology of renal insufficiency, age, gender, and immunosuppressive drugs. Among the risk factors studied, the sole factor showing a statistically significant association with arterial hypertension was the GFR at 3 and 6 months after transplantation. In the group of normotensive patients, GFRs were 92±29 and 83±20 ml/min per 1.73 m² at 3 and 6 months, respectively, whereas in the hypertensive patients, GFRs were 74±23 and 70±21 ml/min per 1.73 m² respectively. Hence, only the lower GFR can be considered a risk factor for hypertension in children within our sample. However, arterial hypertension might be a risk factor for the early onset of chronic allograft nephropathy; in this case, hypertension should be considered the cause of lower glomerular filtration. Our data do not permit us to distinguish between these two hypotheses. The known risk factors for hypertension following renal transplantation in adults were not confirmed in the present study. It remains unclear to us as to whether this means the etiology of hypertension differs in children, or if this is the result of a bias in patient selection.     

Glomerular function and microalbuminuria in children with insulin-dependent diabetes

Renal function has been evaluated in 45 diabetic children (age 12.5±4 years) with a mean diabetes duration of 4.9±3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A₁C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171±31 and 778±172 ml/min per 1.73 m²) compared with controls (124±18 and 631±128 ml/min per 1.73 m²). Both parameters were strongly correlated (r=0.73;P<0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m²) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 g/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA₁C (r=0.35;P<0.05), to mean (r=0.35;P<0.05) and post-prandial blood glucose (r=0.37;P<0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r=0.62;P<0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population.     

Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of⁵¹chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118±33 (SD) to 93±24 ml/min per 1.73 m²] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.     

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.     

Cyclosporine-A-induced nephrotoxicity in children with minimal-change nephrotic syndrome: long-term treatment up to 10 years

The impact of cyclosporine A (CsA) therapy in patients with steroid-dependent nephrotic-syndrome (SDNS) on long-term renal function is controversial. Data beyond 5 years are rare. Long-term renal function was evaluated in children with SDNS with and without CsA therapy, especially beyond 5 years. Twenty children were treated with CsA (study group) for a mean of 5.4 ± 2.2 years (ten patients for 5–11 years). Glomerular filtration rate (GFR) was calculated before and after 3 and 12 months and at latest follow-up of therapy. Fifteen children with cyclophosphamide-treated SDNS without CsA served as controls. In the study group, GFR decreased within 12 months from 136 ± 19 to 120 ± 31, to 114 ± 14 ml/min per 1.73 m² at latest follow-up (p < 0.0001). Patients with CsA > 5 years had a GFR of 111 ± 14 ml/min per 1.73 m² at latest follow-up without a GFR below 90 ml/min per 1.73 m². No CsA toxicity was found in biopsies. In the control group, GFR dropped within 3 months, from 137 ± 27 to 130 ± 24, to 126 ± 19 ml/min per 1.73 m² at latest follow-up (p = 0.1). Patients with and without nephrotoxic CsA therapy showed a drop in GFR. In CsA-treated patients, GFR was about 12% lower at latest follow-up compared with patients without nephrotoxic therapy but always remained within normal range. CsA seems to be safe, even in long-term treatment for more than 5 years.     

Renal function following kidney transplantation in children treated with cyclosporine

The study was performed to evaluate the longterm renal function of children treated with cyclosporine after kidney transplantation. Renal function was determined with clearances of inulin and aminohippurate sodium for evaluating glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Thirty-six children aged 0.4–16.2 (median 6.9) years at transplantation were examined within 5 months of transplantation and then yearly over 0.3–7.1 years. Twenty-five children and young adults, 1.5–20 (median 7.7) years of age, with solitary kidneys because of renal agenesis or nephrectomy, served as controls. The GFR and ERPF within 1 year of transplantation were significantly lower than those of controls (65±19 and 345±88 vs 96±12 and 474±91 ml/min per 1.73 m², respectively). GFR remained constant 4 years after transplantation, but ERPF decreased significantly. Significant inverse correlations were found between GFR within 5 months of transplantation and the mean cyclosporine concentration and the number of rejection episodes. The frequency of hypertension decreased from 82% within 5 months of transplantation to 0% after 4 years. The absolute GFR increased during follow-up. In conclusion, kidney transplantation results in a reduced renal function compared with that of solitary native kidneys. The reduction in renal function correlated with the number of rejection episodes and the cyclosporine load. The increase in absolute GFR during follow-up suggests a remaining capacity for growth and/or compensatory hypertrophy.     

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     

Growth after conversion to alternate-day corticosteroids in children with renal transplants: a single-center study

During the 1980s all children with growth potential and stable/adequate renal function at 6–9 months after kidney transplantation underwent conversion to alternate-day corticosteroids in an attempt to maximize growth. Conversion was attempted in 79 of 160 children who received allografts during this decade and was considered successful if they remained on alternate-day prednisone for more than 1 year, with a calculated creatinine clearance of at least 75% of the pre-conversion baseline value. Conversion succeeded in 55 children but failed in 24. Growth was markedly improved among those successfully converted when compared with the failure group, as measured by standard deviation score for growth velocity based on chronological age (+0.94±1.58 vs. –0.86±1.53,P<0.001) and bone age (+0.49±0.61 vs. –1.24±1.47,P<0.001). The improved growth among the successfully converted patients is believed to have been related to the combined effects of lower corticosteroid dose (0.36±0.16 vs. 0.48±0.21 mg/kg per day,P<0.02) and better renal function (calculated creatinine clearance 87±32 vs. 47±21 ml/min per 1.73 m²,P<0.001) at 1 year post conversion. Two factors appeared to improve the likelihood of successful conversion: the use of cyclosporine and receiving a live-related rather than cadaver transplant. Cyclosporine was associated with improvement in the overall rate for successful conversion in all recipients, from 59% to 83% (P<0.05). Recipients of allografts from live-related donors underwent successful conversion in 90% of cases compared with 58% receiving cadaver allografts (P<0.05). Successful conversion to alternate-day corticosteroid therapy is of significant benefit for linear growth, but may be associated with a risk of rejection and loss of renal function. The risk is small in live-related recipients and has been made safer for cadaver recipients with the introduction of cyclosporine.     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.     

Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil

Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot ⁵¹Cr-EDTA clearance) showed a decline from 131±21 ml/min per 1.73 m² to 116±27 ml/min per 1.73 m² at last follow-up. Similarly, effective renal plasma flow (simultaneous ¹²³I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980±318 ml/min per 1.73 m² to 724±242 ml/min per 1.73 m². In a pilot study we investigated the effect of mycofenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.     

Recombinant human growth hormone in infants and young children with chronic renal insufficiency

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were<2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n=19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n=11) received placebo injections. At entry into the study, the mean (± SD) calculated creatinine clearance was 29.2±14.3 (range 12.0–63.7) ml/min per 1.73 m² in the rhGH-treated group and 23.3±15.1 (range 8.0–59.4) ml/min per 1.73 m² in the placebo-treated group. The 1st year growth rate was 14.1±2.6 cm/year for the rhGH-treated group and 9.3±1.5 cm/year in the placebo-treated group (P<0.00005). During the 2nd year of the study, the growth rate was 8.6±1.2 cm/year in the rhGH-treated group compared with 6.9±1.0 in the placebo groupP=0.025). The height standard deviation score was +2.0±0.7 for the rhGH-treated group compared with –0.2±1.1 in the placebo-treated group (P<0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups. These data suggest that rhGH is efficacious and safe in children with CRI under age 2.5 years. rhGH therapy may correct significant loss of growth at this age when used in conjunction with optimal medical management.     

Postoperative renal function after partial nephrectomy for renal cell carcinoma in patients with pre‐existing chronic kidney disease: A comparison with radical nephrectomy

We assessed whether adequately functioning parenchyma is preserved in patients with pre‐existing chronic kidney disease (CKD) after partial nephrectomy (PN) compared with those who underwent radical nephrectomy (RN). A total of 95 patients with pre‐existing CKD who underwent curative surgery for pathological T1a‐T2N0M0 renal cell carcinoma with a follow‐up period of 12 months or more were the subject of the present study. Of these, 51 patients underwent RN, and 44 PN. Renal function was assessed by using the estimated glomerular filtration rate (e‐GFR). We classified the subjects into two groups according to the preoperative e‐GFR: preoperative e‐GFR 45–59 mL/min/1.73 m² (68 patients); and 30–44 mL/min/1.73 m² (27 patients). In the former group, the probability of freedom from new onset of e‐GFR <45 mL/min/1.73 m² stemmed from the significant difference between the PN and RN groups (P = 0.006; PN: 2 years 64%; RN: 2 years 22%). In contrast, in the latter group, the probability of freedom from new onset of e‐GFR <30 mL/min/1.73 m² was not associated with a significant difference between PN and RN group (P = 0.80). Overall survival and the number of the patients who went on to develop end‐stage renal disease requiring renal replacement therapy between PN and RN were not significantly different in each group. Death from renal cell carcinoma was not noted in either group. PN could significantly prevent development to late‐stage CKD in patients with preoperative e‐GFR 45–59 mL/min/1.73 m² compared with RN. Patients with preoperative e‐GFR 30–44 mL/min/1.73 m² should be reviewed in a more strict study.