Early start to therapy preserves kidney function in spina bifida patients

OBJECTIVE: Renal scarring and renal failure remain life-threatening for children born with spinal dysraphism. We reviewed our data of spina bifida patients to evaluate whether optimal treatment of the neurogenic bladder from birth onwards can preserve kidney function. METHODS: We reviewed data on all newborns with spinal dysraphism who were referred to our hospital between January 1988 and June 2001. We looked at their situations at referral and at follow-up: the type of treatment, antimuscarinic agents, clean intermittent catheterisation (CIC), antibiotic prophylaxis, and operations (sling procedures, bladder augmentations, antireflux procedures). Renal function (ultrasound, DMSA scan, serum creatinin, creatinin clearance) and bladder function (urodynamic studies) were evaluated over time. RESULTS: Data of 144 children of 176 could be evaluated by the end of the study: 5 patients had pre-existing renal abnormalities, 69 had an overactive sphincter, 27 had reflux, and six had renal scarring. None are currently developing end-stage renal disease. All patients with spina bifida aperta started CIC and antimuscarinic therapy shortly after birth. Five of the six patients with renal scarring were started on therapy with intermittent catheterisation and antimuscarinic therapy several months after birth. Sixty-three of 82 children with spina bifida were dry at school age (age six), although 37 of these had not had an operation. CONCLUSION: We show that an early start to therapy helps to safeguard renal function for children born with spina bifida. Our data support other recent reports that children born with spina bifida can probably use their own kidneys for a lifetime, if they are given adequate urological treatment. To protect the upper urinary tract, we need to ensure low intravesical pressure by starting children early on CIC (the preferred treatment); antimuscarinic agents to counteract detrusor instability are indispensable in most cases. Proactive treatment of risks for upper tract deterioration results in a negligible loss of renal function, even when early urinary continence is included in the treatment protocol.     

Differences between ‘intact’ PTH and 1–84 PTH assays in chronic renal failure and dialysis

Intact parathyroid hormone (iPTH) assays overestimate actual PTH as they cross-react with non (1–84) PTH fragments (C-PTH) that accumulate in renal failure. New assays that measure just 1–84 PTH (CAP-PTH) are now available. It has been suggested that there is a linear relationship between the two assays; however, increased C-PTH levels are found as glomerular filtration rate (GFR) declines and in patients on dialysis. We investigated the relationship between iPTH and CAP-PTH in children with chronic renal failure (CRF) managed conservatively and on dialysis. We investigated 241 children, 156 with a GFR <60 ml/min per 1.73 m² managed conservatively, 49 post renal transplant (and GFR <60 ml/min per 1.73 m²) and 36 on dialysis, by measuring PTH levels by iPTH and CAP-PTH assays. Multiple regression analysis comparing differences between PTH levels in each patient group was performed. Correlation slopes between iPTH and CAP-PTH assays differed between CRF and dialysis patients (P=0.001). These assays perform differently in CRF and dialysis patient groups. Studies investigating the correlation between newer assays and bone histology are required to determine whether these more-specific PTH assays are superior surrogate markers of bone turnover.     

Prevention of chronic kidney disease in spina bifida

Objective

The prevalence of progressive chronic kidney disease (CKD) in children and adults with spina bifida is considerable, rising, and entirely preventable.

Removing the cause: prevention of spina bifida

The best prevention of CKD in spina bifida is prevention of spina bifida itself through strategies that include folate supplementation, ideally before pregnancy.

The cause of CKD

Dysfunctional bladder outlet causes febrile Urinary Tract Infections (UTI), even with clean intermittent catheterization (CIC), and subsequent renal scarring. The development of secondary vesicoureteric reflux (VUR) increases the risk of renal scarring and CKD.

Finding the ideal marker for measurement of renal function in spina bifida

Creatinine-based methods are insensitive because of low muscle mass and underdeveloped musculature in the legs. Only Cystatin C?Cbased eGFR can reliably assess global renal function in these patients. However, unilateral renal damage requires nuclear medicine scans, such as ^99mTc DMSA.

(Video)Urodynamics studies (UDS)

Early treatment is recommended based on UDS with anticholinergics, CIC, and antibiotic prophylaxis when indicated. Overnight catheter drainage, Botox, and eventually augmentation cystoplasty are required for poorly compliant bladders. A continent child or one rendered continent following surgery is at a higher risk of renal damage.

Conclusion

A multidisciplinary approach is required to reduce the burden of CKD in patients with spina bifida. The right tools have to be utilized to monitor these patients, particularly if recurrent UTIs occur. Cystatin C eGFR is preferred for monitoring renal damage in these patients, and ^99mTc DMSA scans have to be used to detect unilateral renal scarring.     

Hemolytic uremic syndrome: defining the need for long-term follow-up

BACKGROUND: Diarrhea-associated (D+) hemolytic uremic syndrome (HUS) is a common cause of acute renal failure in children. Progressive renal insufficiency has been documented on prolonged follow-up of selected patients. However, it is uncertain whether all children recovering from varying degrees of HUS require long-term follow-up. PATIENTS AND METHODS: We reviewed the outcome of 114 patients with D+ HUS presenting to a regional pediatric unit between January 1986 and December 1996. Yearly clinical review post illness included measurement of blood pressure and urinalysis for proteinuria with planned GFR assessments by 51Cr EDTA slope clearance at 1 and 5 years. RESULTS: Treatment of the HUS was conservative in 27%, by peritoneal dialysis in 62%, hemodialysis in 4% and both peritoneal and hemodialysis in 7%. Ninety-two patients were assessed at 1 year - of these, 1 remained on chronic peritoneal dialysis, 5 (5%) had moderate to severe chronic renal failure (CRF) (GFR 25 - 50 ml/min/1.73 m2), 20 (22%) had mild CRF (GFR 50-80) and 66 (72%) had normal renal function (> or =80 ml/min/1.73 m2). Forty patients have had GFRs performed at 1 and 5 years. Of the 28 patients with a normal GFR at 1 year, 3 deteriorated into mild CRF at 5 years. One patient has a single kidney and one had significant proteinuria at 1 year, factors which would have led to long-term follow-up. There was a negative correlation between number of days of dialysis and GFR at 1 year with a Pearson's correlation coefficient of -0.453 (p<0.01). CONCLUSION: We conclude that renal function at I year following HUS cannot be predicted with any certainty from the initial illness and should be formally assessed. However, renal function was within normal limits and remained stable between 1 and 5 years following HUS in most children. The results suggest that longer-term follow-up can probably be restricted to those with proteinuria, hypertension, abnormal ultrasound and/or impaired GFR at 1 year.     

Role of urologic evaluation in the adult spina bifida patient

OBJECTIVE: To evaluate a population of adult spina bifida patients performing clean intermittent catheterization (CIC) and determine the indications for urologic consultation and intervention. METHODS: We evaluated 52 adults (ages 18-37 years) with a history of lumbar myelomeningocele, all of whom performed CIC and were dry between catheterizations. We excluded 12 patients with conditions potentially predisposing to renal insufficiency (staghorn calculus, n = 3; multiple admissions for pyelonephritis, n = 5; history of vesicoureteral reflux, n = 2, and renal scarring on ultrasound, n = 2), leaving 40 patients evaluable. Each patient kept a catheterization diary for 2 weeks from which an average catheterized volume was recorded. RESULTS: In patients with normal ultrasound and normal serum creatinine (<1.5 mg/dl), there were no individuals (0/20) whose average catheterized volume corresponded to a bladder pressure of >40 cm H(2)O on cystometry. However, in the patients with hydronephrosis and/or elevated creatinine, 30% (6/20) had average catheterized volumes corresponding to a bladder pressure of >40 cm H(2)O, and are therefore theoretically at risk for upper tract deterioration. CONCLUSION: Many spina bifida patients receive urologic care only as children, and those without urinary calculi or urinary incontinence are assumed to be urologically stable. However, certain patients have urodynamic parameters which put them at risk for renal deterioration even if they appear to be problem-free. We recommend a yearly renal ultrasound and serum creatinine determination in all adult spina bifida patients with immediate urologic consultation and urodynamics if either is abnormal.     

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     

Renal Function and Serum Albumin at the Start of Dialysis in 514 Chinese ESRD In-Patients

Background. The dialysis population has grown rapidly in recent decades. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are scant data about the level of renal function and the relationship of renal function and serum albumin at the start of dialysis in Chinese ESRD patients. Method. We report the level of serum creatinine (Scr), glomerular filtration rate (GFR), and serum albumin (Salb) in 514 ESRD in-patients who began their dialysis treatment between January 2001 through December 2007 at two large dialysis centers in Changsha, Hunan, China. Data were obtained through reviewing the case records of all 514 patients. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. In addition, serum albumin was analyzed in relation to levels of predicted GFR. Results. The mean (SD) and median predialysis serum creatinine was 1121.92 ± 458.24 and 1032 μmol/L. The mean (SD) and median predicted GFR was 4.98 ± 2.24 and 4.47mL/min/1.73m². The proportion of patients with predicted GFR of >10, 5 to 10, and <5 mL/min/1.73m² was 3.7, 36.2, and 60.1%, respectively. The mean predicted GFR was significantly lower among younger patients, uninsured patients, unemployed or farmer patients, patients who were employed, students, patients who selected hemodialysis, patients with ESRD caused by diseases other than diabetes, patients with BUN above the mean, and patients with hemoglobulin beneath the mean. Compared with patients who started with GFR >5mL/min, the patients who started with GFR ≤5mL/min had significantly higher plasma urea and creatinine levels but significantly lower creatinine clearance (mL/min per 1.73m²) and parameters of nutritional status, such as serum albumin, body weight, and BMI. Conclusion. A wide variation existed in renal function at the initiation of dialysis in partial Chinese ESRD patients. Most patients start dialysis at very low levels of predicted GFR. The nutritional status in patients who start dialysis early was better than those in patients who start dialysis when GFR ≤ 5mL/min. Further studies are needed to analyze the impact of level of renal function and nutritional status at the start of dialysis on the outcomes of ESRD.     

Detrusor overactivity in spina bifida: How long does it need to be treated?

AIMS: To determine whether a lasting therapeutic effect can be expected from long-term antimuscarinic therapy for neurogenic detrusor overactivity in spina bifida and to answer the question whether detrusor overactivity in spina bifida children with detrusor/sphincter dyssynergia is primarily based on the neuropathy or, in part, can be a secondary detrusor reaction to the functional urethral obstruction. METHODS: Fifteen spina bifida patients, aged between 1 and 12 years, all on a regime of clean intermittent catheterisation (CIC) and oxybutynin since shortly after birth, underwent three consecutive urodynamic studies (UDS). One prestudy UDS for treatment control, one UDS after withdrawal of oxybutynin for 3-5 days and one UDS after reinstallment of oxybutynin treatment. Urodynamic results were compared concerning detrusor overactivity, cystometric bladder capacity, and compliance. RESULTS: Detrusor overactivity was seen in two patients on the prestudy UDS. After several days of withdrawal of oxybutynin overactivity was seen in 11 patients. After oxybutynin withdrawal, bladder compliance was within safe margins for two patients only, after reinstallment, safe vesical pressures were seen in 11 patients. CONCLUSION: The functional obstruction due to detrusor/sphincter dyssynergia has been by-passed chronically in all these children by CIC and oxybutynin. Due to the fact that detrusor overactivity recurs immediately after withdrawal of medication after long-term treatment with oxybutynin, one can conclude that there is no long-lasting therapeutic effect of pharmacological suppression. This suggests that in children with detrusor/sphincter dyssynergia, detrusor overactivity is primarily of neuropathic origin.     

Delayed bladder rupture after augmentation enterocystoplasty

Delayed bladder perforation with peritonitis following augmentation enterocystoplasty in children with spina bifida is a serious and potentially life-threatening complication. Our experience with 4 such cases is presented. All patients had spina bifida with a neuropathic bladder and they had undergone augmentation enterocystoplasty with a tubular colonic segment of large bowel as part of an undiversion procedure. All patients were being managed with intermittent self-catheterization. The interval from augmentation enterocystoplasty until presentation ranged from 6 months to 3 years. Diagnosis was delayed in all cases, including 3 in which cystogram studies were normal despite findings of extravasation of urine at exploration. In 1 patient generalized sepsis developed with the respiratory distress syndrome and, subsequently, she died.     

Renal size and function in patients with neuropathic bladder due to myelomeningocele: the role of growth hormone

PURPOSE: Patients with spina bifida have smaller kidneys than healthy individuals. We evaluated the correlation between small size and decreased renal function, and the possible role of growth hormone deficiency. MATERIALS AND METHODS: A total of 54 patients (mean age 11.5 years, median 11, standard deviation +/- 4.52) were healthy except for neuropathic bladder due to spina bifida. Renal function was evaluated with mercaptoacetyltriglycine renal scintigraphy and creatinine clearance. Renal anatomy was evaluated with renal ultrasound and voiding cystourethrography. Serum insulin-like growth factor-1 (IGF-1) levels were measured in all patients with immunoradiometric assay. Renal measurements in our patients were compared using the Sutherland nomogram. RESULTS: A total of 22 patients (41%) had smaller kidneys than normal subjects and 31 appeared to have creatinine clearance values lower than 120 ml per minute per 1.73 m2. The statistical comparison between kidney size and creatinine clearance was significant (p <0.05, r = 0.381). Scintigraphic data showed total effective renal plasma flow less than 568 ml per minute per 1.73 m2 body surface area (normal mean value for age). Comparison between effective renal plasma flow and creatinine clearance was significant (p <0.05, r = 0.31). Serum levels of IGF-1 were normal for age in all patients (mean 332.06 ng/ml, median 303.4, range 39.4 to 732.3). CONCLUSIONS: The kidneys are smaller in patients with spina bifida than in healthy subjects when compared using the Sutherland nomogram. There is a significant correlation between smaller renal length and decreased renal function in all patients, even in those who are healthy except for neurogenic bladder secondary to spina bifida. IGF-1 levels were normal for age, and, therefore, these patients had no growth hormone deficiency. These findings call into question the hypothesis that growth hormone deficiency contributes to smaller kidney size. Other hypotheses can be suggested, such as a defect of embryological growth secondary to malformation, or the result of a defect in homocysteine-methionine metabolism.     

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.     

Correlation between cystatin C- and renal scan-determined glomerular filtration rate in children with spina bifida

We report on the relationships between serum cystatin C level, glomerular filtration rate (GFR) estimated from a cystatin C-based prediction equation (that of Filler and Lepage), GFR calculated by the Schwartz formula and technetium 99m-diethylene triamine penta-acetic acid (⁹⁹Tc-DTPA)-determined GFR in 28 children with spina bifida. All children underwent measurement of height, weight, serum cystatin C level, and serum creatinine level at the time of their renal scan. The relationship between variables was assessed by Pearson correlation. Pearson correlation for the relationship between ⁹⁹Tc-DTPA GFR and GFR calculated by the cystatin C-based equation was significant and higher than that of the relationship between ⁹⁹Tc-DTPA GFR and GFR calculated by the Schwartz equation, which was not statistically significant. The correlation for Filler GFR was 0.42 (P = 0.03) and for Schwartz GFR was 0.21 (P = 0.28). Although we use renal scan determination of GFR as the best measure, and a creatinine-based formula as the most practical measure, perhaps a formula such as that published by Filler and Lepage, which is not dependent on anthropometric data, might be a more useful (and accurate) tool for establishing GFR in children with spina bifida.     

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.     

Latex allergy in children with urological malformation and chronic renal failure

PURPOSE: Children with spina bifida, bladder exstrophy and anorectal anomalies are at risk for latex allergy. Severe intraoperative anaphylaxis in a boy treated with kidney transplantation prompted this study to evaluate the prevalence of latex allergy in a cohort of children with chronic renal failure (CRF). MATERIALS AND METHODS: Between 1996 and 2002, 57 boys and 28 girls were investigated at a median age of 10.5 years (range 1.3 to 22.9). Urological malformations were the underlying cause of CRF in 33 patients (39%). Of the patients 39 were on conservative treatment, 20 were on dialysis and 26 had a functioning renal graft. Latex reaction was assessed by a careful history, specific serum latex IgE and skin prick test. RESULTS: A total of 19 patients (22%) showed latex reaction, of whom 8 had allergy (clinical symptoms included severe intraoperative anaphylaxis in 1) and 11 had sensitivity (positive IgE or prick test without symptoms). Of these 19 patients 11 had urological malformations. The number of surgical procedures, young age at operation and atopy were significant risk factors. When operations were analyzed separately, ie urological vs nonurological surgery, only urological surgery was significantly associated with latex reaction. A significant correlation was also found between the overall number of operations and latex radioallergosorbent class. CONCLUSIONS: All children with CRF who undergo early and multiple urological surgery are at high risk for latex reaction. Primary latex prevention, ie the routine use of latex-free gloves, tubes and catheters, should be implemented in all children with complex urological malformations.     

Poor compliance early in filling in the neuropathic bladder

A total of 30 patients with known neuropathy, mostly spina bifida, developed poor bladder compliance early in filling demonstrated urodynamically; 20 had bilateral hydronephrosis at the time of presentation and 5 also had severely impaired renal function. After appropriate treatment all of those with normal upper tracts or with bilateral hydronephrosis but normal renal function stabilised or improved. However, all 5 with severely impaired renal function progressed to end-stage renal failure. Poor compliance early in filling is an absolute indication for surgical intervention.     

Growth in children with chronic renal failure and after renal transplantation

Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation. Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 ± 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 ± 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall’s correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.     

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.)     

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.     

Prevalence of malnutrition in Nigerians with chronic renal failure

In developed countries, malnutrition is common in patients with chronic renal failure (CRF) and has adverse effects on patient morbidity and mortality. The prevalence of malnutrition before the initiation of dialysis is poorly characterized in CRF patients in developing countries. We studied the prevalence of malnutrition among Nigerians with CRF before commencement of dialysis. Body mass index (BMI) and serum protein levels were measured in 74 dialysis naïve Nigerians with CRF and 48 controls. Patients with nephrotic syndrome, steroid use and failure of organs other than the kidneys were excluded. The mean BMI was significantly lower in the patients compared to the controls (22.4 ± 14.9 kg/M² Vs. 25.2 ± 2.7 kg/M²; p = 0.0001). Low BMI (less than 20 Kg/M²) was present in 16 (21.6%) of the patients compared with one of the controls. The mean serum total protein and albumin were also significantly lower in the patients compared to controls (61.9 ± 14.4 g/L Vs. 73.8 ± 6.8 g/L; p < 0.0001, and 31.5 ± 9.3 g/L Vs. 39.6 ± 4.4 g/L; p < 0.0001 respectively). Protein malnutrition (serum albumin < 29 g/L) was present in 32 (43.2%) of patients with CRF and one (2.1%) of the control subjects. Malnutrition is common in Nigerian CRF patients before the commencement of dialysis. In these patients, emphasis should be placed on prevention and/or correction of malnutrition because of its documented adverse effects on the outcomes of maintenance dialysis.     

The consequence after introduction of clean intermittent catheterization (CIC) in children with neurogenic bladder dysfunction secondary to spina bifida--the comparison of patients with and without upper urinary tract dilation at the time CIC was introduced

PURPOSE: The aim of current study was to review the consequence after introduction of clean intermittent catheterization (CIC) in children with neurogenic bladder dysfunction secondary to spina bifida. PATIENTS AND METHODS: We retrospectively reviewed the records of 34 children (19 girls and 15 boys) presenting our clinic in a 18-year period. The patients were divided concentrating on the radiological upper urinary tract findings when CIC was introduced. 18 children had dilated upper urinary tract. In these patients, 10 children already had dilated upper urinary tract at first visiting to our clinic(group A). In remaining 8 patients, dilatation of upper urinary tract was found out in the course of followup (group B). 16 children had normal upper urinary tract when CIC was introduced. In 7 patients, CIC was applied for post-void residual and urinary tract infection (group C). In remaining 9 patients, CIC was introduced for urodynamically low compliance bladder (group D). RESULTS: In group A, 5 patients underwent enterocystoplasty and 3 patients underwent anti-reflux surgery consequently. Two patients, including 1 patient who underwent enterocystoplasty, have chronic renal dysfunction. In group B, 3 patients underwent enterocystoplasty and 2 patients underwent anti-reflux surgery. In group C, all patients have normal upper urinary tract. In group D, 8 patients have normal upper urinary tract. However, 1 patients underwent enterocystoplasty for low compliance bladder with vesicoureteral reflux (VUR). CONCLUSION: Some patients show the improvement of dilated upper urinary tract or VUR after introduction of CIC. However, enterocystoplasty or anti-reflux surgery was needed for many patients to prevent upper urinary tract deterioration. The patients whom CIC was introduced for postvoid residual and urinary tract infection have not shown any deterioration of upper urinary tract. The efficacy of CIC for incontinence was poor because many patients have urethral sphincter incompetence.