Reduced taste function and taste papillae density in children with chronic kidney disease.

BACKGROUND: Taste loss may contribute to the loss of appetite in children with chronic kidney disease (CKD) and other serious medical conditions that result in malnutrition. Traditional methods for measurement of taste loss commonly use aqueous tastant solutions that can induce nausea, vomiting, or even pain in the mouth. An alternative is to measure fungiform papillae density on the anterior tongue since this correlates with taste sensitivity. Here we aimed to develop a non-invasive method for assessing papillae density on the anterior tongue and to use the method to determine if CKD patients [estimated glomerular filtrate (eGFR < 60 ml/min/1.73 m(2))] have a lower density than clinical controls (CC)(eGFR > 89 ml/min/1.73 m(2)). METHODS: Thirty-five healthy adults participated in the development of a method, which was assessed by 24 children, 12 of whom were CKD patients and 12 were clinical controls. RESULTS: Similar papillae densities were found using invasive and non-invasive methods (F(1,34) = 0.647, p = 0.427). The CKD group had a significantly lower papillae density (X(2) = 7.17, p = 0.007) and poorer taste sensitivity than the CC group (p = 0.0272), and the density correlated significantly with eGFR (r = 0.56, p < 0.01). CONCLUSIONS: Loss of taste in children with CKD is due to the reduced number of papillae and their taste-sensing receptor cells.

Causes and outcome of late referral of children who develop end-stage kidney disease.

AIMS: This study aims to characterise the timing of referral to a paediatric nephrology unit of children who develop end-stage kidney disease (ESKD). This study also aims to determine whether late referral (LR) influences outcomes and to explore factors that may lead to LR. METHODS: A retrospective case review of all incident patients with ESKD who received renal replacement therapy (RRT) at a single paediatric centre. Time between referral to a paediatric nephrologist and commencement of RRT, demographic and clinical data were collated. Estimated glomerular filtration rate (eGFR) at referral was calculated using height and creatinine. LR was defined as having an eGFR ≤ 30 mL/min/1.73 m(2) when first seen by a paediatric nephrologist. RESULTS: RRT was initiated for 74 patients < 18 years of age between 1988 and 2010. The median age at referral was 2.0 years (birth-15.9 years) and age at RRT was 10.0 years (6 days-17.4 years). Children referred before age 1 year (41%) had a more prolonged course before ESKD. Median (interquartile range) eGFR at referral of children > 1 year was 27.2 (9.0-52.0) mL/min/1.73 m(2) . Twenty-two (55%) of these children were referred late (LR) with an eGFR ≤ 30 mL/min/1.73 m(2) . LR patients were more likely to have glomerulonephritis or haemolytic uraemic syndrome and to live in a remote or outer regional area. LR patients had higher urea, lower haemoglobin and were more likely to receive haemodialysis via a vascular catheter. CONCLUSIONS: A significant proportion of children who develop ESKD are referred late to nephrology units with potentially preventable complications. Aetiology of renal disease and geographic isolation contribute to LR.

Smell and taste function in children with chronic kidney disease.

Loss of appetite and poor growth are common in children with chronic kidney disease (CKD), and changes in smell and/or taste function may be responsible, but the hypothesis has not been proven. This aims of this prospective age- and gender-controlled study were to determine whether: (1) changes in smell and taste function occur in children with CKD; (2) smell or taste dysfunction are associated with estimated glomerular filtration rate (eGFR); (3) there is an association between smell or taste loss and body mass index (BMI). The study cohort consisted of 72 children of whom 20 were CKD stage 3-5 patients, 12 were CKD stage 2 patients, 20 were clinical controls (CC) and 20 were healthy children (HC). The CKD patients and clinical controls were recruited from Sydney Children's Hospital and The Children's Hospital, Westmead, and healthy controls were recruited from a local school. Scores for each group from taste and smell chemosensory function tests were compared, and their relationship with renal function and BMI investigated. The CKD stage 3-5 group had a significantly lower taste identification score (85.6%, P < 0.001) than the CC (94.8%) and HC (94.8%) groups, with almost one third of the children in the CKD stage 3-5 group exhibiting taste loss. Decreased taste function was associated with decreased eGFR (r = 0.43, P < 0.01), but no association between BMI and taste function was found (r = 0.001, P > 0.9). Odour identification scores were not different; however, there was a positive relationship with BMI (r = 0.427, P = 0.006). We conclude that a loss of taste can occur in children with CKD and that when it occurs, it worsens as eGFR declines and is found early in kidney disease.

Acquired facial palsy with hypertension secondary to Guillain-Barre syndrome.

Most cases of facial nerve paresis are idiopathic (Bell's palsy). However, rare and potentially dangerous conditions may present in this manner. We report 2 children presenting with unilateral lower motor neuron facial nerve palsy and hypertension. A diagnosis of Guillain-Barre syndrome was made in both; literature linking facial nerve palsy in childhood with hypertension and Guillain-Barre syndrome is reviewed.

Renal length discrepancy by ultrasound is a reliable predictor of an abnormal DMSA scan in children.

A renal length discrepancy (RLD) of more than 10 mm by ultrasound (US) is accepted as a potential indicator of an underlying renal pathology; however, there are few supporting data for this in children. Our objective was to determine a cutoff at which RLD on US is a reliable predictor of dimercaptosuccinate acid (DMSA) scan abnormality. We present data from 90 patients who had both renal US and a DMSA scan, as well as DMSA scan results compared with bipolar RLD by US. Positive (PPV) and negative (NPV) predictive values were calculated for renal RLD from 6 to >10 mm. The left kidney was longer in 56%, whereas the right kidney was longer in 37%; their lengths were equal in 8%. For children at all ages, a left kidney longer than the right by >or=10 mm or a right kidney longer than the left by >or=7 mm gave a PPV for DMSA abnormality of 79% and 100%, respectively. In children older than 4 years, if the right kidney was longer by >or=7 mm or if the left kidney was longer by >or=10 mm, the PPVs for DMSA abnormality were 100% and 63%, respectively. In children younger than 4 years, when the right kidney was longer by >or=6 mm or the left was kidney longer by >or=10 mm, the PPV were 86% and 100%, respectively. Thus, children with a right kidney longer than the left by even <10 mm is a reliable predictor of an abnormal DMSA scan.

The choice of threshold limits for pediatric ambulatory blood pressure monitoring influences clinical decisions.

OBJECTIVES: Hypertension in children may be defined by blood pressure elevated above the 95th percentile according to sex and age. Population data for ambulatory blood pressure provide different age-related and sex-related threshold limits to office-derived data. We sought to determine whether, when using ambulatory blood pressure monitoring in a clinical setting, changing 95th percentile threshold limit sets from office-derived to ambulatory blood pressure-derived would lead to different diagnostic decisions. METHODS: Three nephrologists who were blinded as to patient identity and limit setting method reported on 42 ambulatory blood pressure records from a mixed group of patients aged 5-18 years by using both office-derived threshold limits for the 95th centile of blood pressure and ambulatory blood pressure-derived limits. Decisions regarding the presence or absence of hypertension were compared for each patient according to the limit set. RESULTS: Thirty-five (83%) patients were considered to be hypertensive when office-derived threshold limits were used and 20% (P=0.005) fewer records were reported as showing hypertension when ambulatory blood pressure-derived threshold limits were used. When ambulatory blood pressure limits were applied, there were fewer records with an awake systolic blood pressure load >50% (P=0.004) and the average awake systolic blood pressure load was significantly lower (P<0.001). CONCLUSION: Ambulatory blood pressure normative data tend to provide higher blood pressure limits for age and sex. Consequently, when ambulatory blood pressure data are used to set threshold limits, clinical decisions based on ambulatory blood pressure may be different than when office limits are used. These findings demonstrate the importance of using the most appropriate limit sets to analyze ambulatory blood pressure and when interpreting ambulatory blood pressure-based research.

Cyclosporine formulation and Kaposi's sarcoma after renal transplantation.

BACKGROUND: Transplantation enhances the risk of malignancies, due to the chronic use of antirejection medication. In the case of Kaposi's sarcoma (KS) the permissive effect of immunosuppression has been extensively studied, and cyclosporine (CsA) appears to play a key role. Here we have compared the incidence of KS in transplant patients receiving Neoral or Sandimmune as a part of their immunosuppressive therapy. METHODS: In all, 668 kidney transplant recipient followed at our Nephrology Unit from 1970 to 2003 entered this retrospective analysis; 300 were on CsA Sandimmune-based and 308 on CsA Neoral-based therapy. The primary endpoint was the occurrence of KS. RESULTS: KS was diagnosed in 20 out of 608 patients given CsA with an incidence rate of 4.7 per 1000 patients per year. No episodes of KS was found in the preCsA era. Among patients on CsA, those treated with Neoral had fourfold higher incidence rate of KS than in the Sandimmune group (10.7 vs. 2.3 per 1000 patients per year). Kaplan-Meier analysis shows that patients on Neoral had lower cumulative KS-free probability than those on Sandimmune. Cox's analysis documented that Neoral was a positive predictor of KS development as compared to Sandimmune (hazard ratio: 2.237). Among patients on Neoral, those who developed KS had higher daily exposure to the drug assessed by pharmacokinetic studies. CONCLUSIONS: In recipients of kidney transplant CsA Neoral increases the risk of KS as compared to the Sandimmune formulation, possibly due to enhanced drug bioavailability and ultimately patients daily CsA exposure.

Agreement on reporting of ambulatory blood pressure monitoring in children.

The use of ambulatory blood pressure monitoring (ABPM) can improve the accuracy of paediatric BP measurement and may better correlate with end-organ injury than office BP measurement. However, the interpretation of ABPM may be influenced by several variables. We sought to ascertain the agreement among three paediatric nephrologists when reporting 92 ABPM sessions performed on patients aged 5 to 18 years. All three nephrologists were in agreement on the presence or absence of hypertension in 64% of cases. They were less likely to concur about records where hypertension was borderline or if the ABP record contained fewer BP readings. These results highlight the need for evidence-based consensus regarding the interpretation of ABPM in children.

Renal scintigraphy unraveled the diagnostic dilemma of antenatal hydronephrotic solitary kidney-crossed renal ectopia.

On antenatal ultrasound assessment, an apparently solitary hydronephrotic kidney was identified, confirmed on postnatal ultrasound examination. More detailed postnatal investigations revealed the diagnosis of crossed renal ectopia.

Retinoic acid may increase the risk of bone marrow transplant nephropathy.

Bone marrow transplant nephropathy (BMTN) classically presents more than 100 days after transplantation as an acute nephritis with hypertension, azotaemia and anemia that usually results in end stage renal failure (ESRF). The risk of developing BMTN may be greater with the use of more intensive chemotherapy and higher total body and tumor bed irradiation. Cis-retinoic acid (RA) may further increase the risk of developing BMTN. Here, we report the cases of two children who developed typical clinical and biochemical features of BMTN. They were both treated for stage IV neuroblastoma with chemotherapy, bone marrow transplant (BMT) conditioning that included total body irradiation and RA therapy after BMT, although the patient in case 1 had established renal insufficiency prior to the commencement of RA. Renal biopsy of these children showed classical BMTN histology, and the renal manifestations progressed quickly; the patient in case 1 became dialysis dependent by 1 year post-bone marrow transplant. Recently, RA has been added to the post-BMT therapy in children with stage IV neuroblastoma. The occurrence of BMTN in two children treated with RA in our unit is unlikely to be coincidental. Although RA has been shown to confer a significant survival advantage in this disease, animal studies and a previous case report have suggested it could increase the toxic effects of chemotherapy and renal irradiation. It is likely that RA contributed to the deterioration in renal function in these patients.

Collection under paraffin is not necessary for stability of urine pH over 24 h.

Collection of urine under paraffin is routinely used in clinical practice for urine pH evaluation. To examine whether the accuracy of pH measurement is adversely influenced by the method of collection and storage, we divided each urine specimen and sent one aliquot to the laboratory under paraffin and another in a sealed 5-ml plastic syringe. In another experiment we evaluated the stability of urine pH measurement in a clinical setting. Urine collected under paraffin was tested immediately for pH; an aliquot from the same specimen was stored in a capped 5-ml syringe at 4 degrees C and tested after 24 h. We found no appreciable difference in measured pH between samples sent to the laboratory under paraffin or in a capped plastic syringe.

Clinical, histopathologic, and genetic studies in nine families with focal segmental glomerulosclerosis.

BACKGROUND: Familial forms of focal segmental glomerulosclerosis (FSGS) are caused by mutations in genes at 1q25-31 (gene for steroid-resistant nephrotic syndrome 2 [NPHS2]), 11q21-22, 19q13 (gene for alpha-actinin 4 and NPHS1), and at additional unidentified chromosomal loci. METHODS: We describe clinical and histopathologic features and results of linkage analysis in nine consecutive index cases with familial FSGS who, together with their families, were referred for genetic studies. RESULTS: Two of the index cases presented in childhood (22%) and seven cases presented in adolescence or adulthood (78%). Six of their families (67%), including the two cases with childhood-onset disease, showed probable autosomal recessive inheritance. FSGS segregated at the 1q25-31 locus in two of these families and at the 11q21-22 locus in four families. None had disease caused by mutations in genes at the 19q13 locus, and no locus was identified in the three remaining families. Clinical features of proteinuria, minimal hematuria, hypertension, preeclampsia, and progressive renal impairment were usually present with autosomal recessive or dominant inheritance and with disease that segregated at the different loci. Eighteen renal biopsies from affected members of eight families showed a strong correlation between tubulointerstitial damage and percentage of obsolescent glomeruli (rho = +0.76; P < 0.01). None of the 13 patients from eight families who underwent transplantation developed recurrent FSGS in their grafts. In general, carriers of autosomal recessive disease had no distinctive clinical features apart from the development of preeclampsia in successive pregnancies. CONCLUSION: Familial forms of FSGS are not uncommon, and presentation frequently is in adolescence or adulthood, even when inheritance is autosomal recessive. Furthermore, carriers of autosomal recessive FSGS often have no distinctive phenotype.

Atorvastatin treatment for hyperlipidemia in pediatric renal transplant recipients.

The objective of this prospective study was to determine the prevalence of hyperlipidemia in our pediatric renal transplant patients and to treat those with persistently elevated cholesterol and/or low-density lipoprotein (LDL) levels. All patients with a functioning renal allograft for greater than 6 months were studied (n = 18). Patients with cholesterol and/or LDL levels greater than the 95th percentile (n = 9) were commenced on an HMG-CoA reductase inhibitor, Atorvastatin and monitoring was performed for efficacy and adverse effects. Total serum cholesterol was elevated in 11 of 18 (61%) and triglyceride (TG) was elevated in 12 of 18 (67%) patients. Atorvastatin treatment was effective with a mean percentage reduction of total cholesterol of 41 +/- 10% (p < 0.01 vs. before treatment), LDL 57 +/- 7% (p < 0.01 vs. before treatment) and TG 44 +/-25% (p = 0.05 vs. before treatment). No adverse effects on allograft function or cyclosporin levels were experienced. Hyperlipidemia is a common problem and Atorvastatin is a safe and effective treatment in pediatric renal transplant recipients.

The relationship between serum creatinine, serum cystatin C and glomerular filtration rate in pediatric renal transplant recipients: a pilot study.

Serum cystatin C more accurately reflects glomerular filtration rate (GFR) in pediatric renal transplant recipients than serum creatinine. Nineteen pediatric renal transplant recipients, 15 male and 4 female, ranging in age from 8.35 yr to 19.06 yr (median 13.52 yr), were enrolled in the study over an 18-month period. Twenty-eight measurements of 99mTc-DTPA GFR were compared with simultaneous measurements of serum cystatin C and Cr. Linear regression analysis, Pearson correlation coefficients and analysis of variance (anova) were used to determine the relationship between creatinine, cystatin C and GFR. The correlation coefficients (R2) for the relationship of 1/Cr to DTPA-GFR and for 1/cystatin C to DTPA-GFR were 0.63 and 0.58, respectively. There was no significant difference between serum cystatin C and serum creatinine as markers of GFR. Serum cystatin C, which costs more to measure than serum creatinine, offers no advantage in monitoring the renal function of pediatric renal transplant recipients.