Growth hormone improves growth rate and preserves renal function in Dent disease.

Dent disease, an X-linked recessive renal tubular disease, results from loss-of-function mutations in the CLCN5 chloride channel gene. The effects of Dent disease on growth have not been described. We report siblings who presented with proteinuria, calciuria, and phosphaturia and growth failure who responded to growth hormone (GH) treatment. Genotyping revealed a novel c.2179delG frameshift mutation at codon 727, exon 12 of the CLCNS gene. Two years after initial presentation, linear growth had slowed, and evaluation revealed isolated GH deficiency. GH therapy resulted in more than two-fold increases in height velocity and serum IGF-I levels. There was no net change in estimated glomerular filtration rate, proteinuria or calciuria in response to GH therapy, but there was a delayed improvement in phosphaturia. These cases provide insight into the effects of GH on growth and renal function in Dent disease. Furthermore, we have reported a novel CLCN5 mutation.

Acute infection-related glomerulonephritis with disseminated gonococcal infection in a 13-year-old girl.

Infection-related glomerulonephritis results from glomerular immune complex deposition due to a variety of potential pathogens. Poststreptococcal glomerulonephritis is the best known example. We present a case of acute infection-related glomerulonephritis associated with disseminated gonococcal infection in a sexually active 13-year-old girl, the first report of such an association in the absence of endocarditis. The patient presented with features of acute disseminated gonococcal infection including fever, hypotension, tenosynovitis, polyarthralgias and petechiae. She developed hypocomplementemic glomerulonephritis synchronous with the acute infection. The renal biopsy revealed a diffuse endocapillary proliferative and exudative glomerulonephritis with subepithelial electron-dense humps and granular glomerular capillary wall staining for C3 and IgG, typical of acute postinfectious glomerulonephritis. After treatment and resolution of the gonococcal infection, the serum creatinine, complement levels and urine sediment normalised. The only residual renal damage 16 months later was low-grade proteinuria.

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome. METHODS: A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988-2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation. RESULTS: 13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 +/- 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 +/- 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications - prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 +/- 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 +/- 3.1. The mean GFRe was 127 +/- 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive. CONCLUSION: IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.

Urolithiasis in pediatric patients: a single center study of incidence, clinical presentation and outcome.

PURPOSE: The incidence of kidney stones in adults has increased in the last 30 years. This retrospective, single site review was done to test the hypotheses that the incidence of urolithiasis in pediatric patients increased from 1994 to 2005, and that metabolic abnormalities were more common in patients with renal stones in the final 3 years of the study period. MATERIALS AND METHODS: Charts from 2 time periods were reviewed, 1994 to 1996 (period 1) and 2003 to 2005 (period 2). Clinical and laboratory data, including demographics, presenting complaints, laboratory assessment, treatment and outcome, were tabulated in patients with confirmed urolithiasis. RESULTS: The number of patients with urolithiasis increased from 7 in period 1 to 61 in period 2. When expressed as cases per 100 new patients the incidence increased 4.6 times (p = 0.014). Focusing on period 2, 28% of patients were younger than 10 years. While blood tests were generally normal, 76% of patients had at least 1 abnormality in the 24-hour urine collection. Hypocitraturia, which was the most common metabolic abnormality, was noted in 52% of patients. The small number of patients in period 1 precluded determination as to whether metabolic abnormalities were more common in period 2. Surgery and/or lithotripsy was required in 12 children. Stone disease recurred in 39% of the patients. CONCLUSIONS: The incidence of urolithiasis in the pediatric population increased nearly 5-fold at our institution during the last decade. We recommend that the primary diagnostic test be a 24-hour urine collection. The most common metabolic abnormality was hypocitraturia, followed by hypercalciuria. Recurrence of stones is common (approximately 40% rate) and followup is advised.

The association of anemia and hypoalbuminemia with accelerated decline in GFR among adolescents with chronic kidney disease.

We sought to describe rates of kidney function decline and to identify modifiable risk factors for CKD progression in a multicenter prospective cohort study of adolescents with CKD aged 11 to 18 years seen semiannually for up to three years. Of the 23 subjects meeting inclusion criteria, the average estimated GFR was 51 +/- 27 ml/min/1.73 m(2) (0.85 +/- 0.45 ml/s/1.73 m(2)) at entry. The overall annualized decline in GFR was 5.6 ml/min/1.73 m(2) (0.093 ml/s/1.73 m(2)) per year (95% confidence interval [95% CI]: 1.9 to 9.3 [0.032 to 0.16]). The adjusted annualized decline in GFR was found to be accelerated in males, as well as among those over 15 years of age. The adjusted annualized decline in GFR was greater among those with either anemia (hematocrit below 36%), or hypoalbuminemia (albumin below 4 g/dl [40 g/L]). After adjustment, anemia was associated with an accelerated decline of 7.8 ml/min/1.73 m(2) (0.13 ml/s/1.73 m(2)) (95% CI: 3.3 to 12 [0.055 to 0.20]) and hypoalbuminemia was associated with an accelerated decline of 17 ml/min/1.73 m(2) (0.28 ml/s/1.73 m(2)) (95% CI: 11 to 22 [0.18 to 0.37]). Further study is needed to evaluate whether treatment of anemia or hypoalbuminemia, as outlined in current clinical care guidelines for CKD, may slow the progression of CKD in adolescents.

Assessing health status and health care utilization in adolescents with chronic kidney disease.

Few validated health status measures have been assessed in children with chronic kidney disease (CKD). The objective was to assess the validity of a generic health status measure, the Child Health and Illness Profile-Adolescent Edition (CHIP-AE), in adolescents with CKD. A case-control study was performed (1) to assess scores on the CHIP-AE in adolescents with CKD compared with two control groups of age-, socioeconomic-, and gender-matched peers and (2) to compare health of patients who had chronic renal insufficiency (CRI), were on dialysis, and were posttransplantation. Seven pediatric nephrology centers recruited 113 patients (mean age, 14 yr; 39 CRI, 21 dialysis, 53 posttransplantation). Compared with 226 control subjects, patients with CKD had lower overall satisfaction with health and more restriction in activity. Positively, patients with CKD had more family involvement, better home safety and health practices, and better social problem-solving skills and were less likely to participate in risky social behaviors or socialize with peers who engaged in risky behavior. Patients who received dialysis were less physically active and experienced more physical discomfort and limitations in activities than did transplant or CRI patients. It is concluded that patients with CKD have poorer functional health status than age-matched peers. Among CKD patients, dialysis patients have the poorest functional health status. These results suggest that the CHIP-AE can be used to measure functional health status in adolescent patients with CKD.

Prevalence of diurnal voiding symptoms and difficult arousal from sleep in children with nocturnal enuresis.

PURPOSE: We analyzed the relative contribution of detrusor instability and difficult arousal from sleep in the genesis of nocturnal enuresis (NE), and evaluate a clinical feature that may prospectively help differentiate patients with monosymptomatic NE (mono NE) from those with diurnal voiding symptoms (DVSs) of urgency and urge incontinence associated with NE (NE + DVSs). MATERIALS AND METHODS: Patients referred for voiding problems and 627 controls were evaluated for NE, DVSs, nocturia and arousal from sleep on a scale of 1 to 8. Patients were categorized into 3 groups-mono NE of primary or secondary onset (200, boys 71%, girls 29%), primary or secondary NE + DVSs (329, boys 43%, girls 57%) and isolated DVSs (146, boys 21%, girls 79%). RESULTS: DVSs were noted in 49% of boys and 76% of girls with NE, although 40% of patients or parents did not complain of DVSs. The DVSs were elicited on detailed interrogation or on finding evidence of urinary incontinence on perineal examination. While one-third of controls and patients with isolated DVSs manifested nocturia at least twice a month, only 6% of bedwetters did so. Difficult arousal from sleep (scores 6 to 8) was more prevalent in patients with NE (59%) than controls (20%) or patients with isolated DVSs (5%), and in patients with mono NE and primary NE than in NE + DVSs or secondary NE, with reverse prevalence for nocturia. Easy sleep arousal (scores 1 to 3) was noted in 65% of patients with secondary NE + DVSs vs up to 6% of other NE subgroups. Compared to patients with mono NE, those with NE + DVSs had a higher prevalence of urinary tract infection (UTI), encopresis, psychosocial/learning problems, and family history of UTI and DVSs, ie problems associated with detrusor instability. CONCLUSIONS: DVSs accompany NE in two-thirds of patients but can be missed during a cursory history. Difficult sleep arousal seems to have a major role in primary mono NE, and detrusor instability in secondary NE + DVSs. In patients with NE a history of frequent nocturia, easy sleep arousal, UTI, encopresis, psychosocial learning problems or family history of UTI and DVSs should raise the suspicion for associated undisclosed DVSs.

Giggle incontinence in children: a manifestation of detrusor instability.

PURPOSE: To our knowledge the prevalence and cause of giggle incontinence in children is not known. We hypothesized that laughter may induce unstable detrusor contractions in children susceptible to detrusor instability. We evaluated the prevalence of diurnal voiding symptoms of urinary urgency, urge incontinence, pelvic withholding maneuvers and hesitancy in patients with giggle incontinence, the prevalence of giggle incontinence in patients with diurnal voiding symptoms, the prevalence of the 2 conditions in first degree relatives of patients with giggle incontinence, the influence of treatment for detrusor instability on the frequency of giggle incontinence and the prevalence of diurnal voiding symptoms in control children with giggle incontinence. MATERIALS AND METHODS: Of 1,421 children 5 to 15 years old referred to the pediatric nephrology department for various problems 109 were diagnosed with giggle incontinence and 460 had diurnal voiding symptoms. A total of 627 children visiting the pediatrician office whose parents completed a survey questionnaire served as controls. RESULTS: Diurnal voiding symptoms were noted in 95% of the patients with giggle incontinence, while giggle incontinence was noted in 23% of those with diurnal voiding symptoms. Of the patients with giggle incontinence a positive family history for that entity and diurnal voiding symptoms was noted in 13% and 28%, respectively. Giggle incontinence improved in all patients after treatment for detrusor instability and it resolved completely in 89%. Giggle incontinence recurred with a relapse of diurnal voiding symptoms in 28 cases and improved with improved diurnal voiding symptoms during modification of therapy. Diurnal voiding symptoms were present in 43% of the 157 controls with giggle incontinence. CONCLUSIONS: Giggle incontinence results from detrusor instability induced by laughter and it improves with effective treatment of detrusor instability.