Renal Tubular Dysfunction Fully Accounts for Plasma Biochemical Abnormalities in Type 1A Pseudohypoparathyroidism.

Context: Type 1A pseudohypoparathyroidism (PHP-1A) is characterized by target organ resistance to PTH. Patients can present with various dysmorphic features; however, renal failure has not been classically described. Case Description: A female patient came to our attention at the age of 7 years with characteristic signs of PTH resistance (i.e., hypocalcemia, hyperphosphatemia, and high serum PTH levels). She also presented with hypothyroidism, early-onset obesity, short metacarpal bones, and multiple subcutaneous ossifications, leading to a clinical diagnosis of pseudohypoparathyroidism. In addition to her genetic condition, she had bilateral renal hypodysplasia that was slowly progressing to end-stage kidney disease. She received a kidney transplant at the age of 16 years and, after transplantation, experienced rapidly normalized calcium, phosphate, and PTH levels, allowing f withdrawal of vitamin D supplementation. Conclusions: To the best of our knowledge, ours is the first report of a patient with PHP-1A undergoing kidney transplantation. Normalization of biochemical parameters after the procedure demonstrated that renal tubular resistance to PTH is sufficient to explain the calcium/phosphate abnormalities observed in PHP-1A.

Anterior ischemic optical neuropathy in children on chronic peritoneal dialysis: report of 7 cases.

BACKGROUND: Anterior ischemic optic neuropathy (AION) is characterized by infarction of the optic nerve head due to hypoperfusion of the posterior ciliary arteries and causes sudden blindness in adults on chronic dialysis, but has rarely been described in children. Unlike adults, children do not have comorbidities related to aging. METHODS: We retrospectively analyzed data of 7 children on nocturnal continuous cycling peritoneal dialysis (CCPD) who developed AION identified within the Italian Registry of Pediatric Chronic Dialysis. We also summarized data from 10 cases reported in the literature. RESULTS: Our 7 patients suffered from acute onset bilateral blindness. Their mean age was 3.2 years and chronic hypotension had been observed prior the AION in 3 of the 7 children. Low systolic blood pressure (SBP) was associated with higher risk of developing AION according to statistical analysis. None recovered completely. In total, 11 out of 16 experienced a partial recovery and no clear evidence emerged favoring specific treatments. CONCLUSIONS: Hypotensive children treated with CCPD are at increased risk of developing AION, which often results in irreversible blindness.

Parathyroid hormone levels in long-term renal transplant children and adolescents.

Secondary hyperparathyroidism is a common complication of chronic renal failure. Kidney transplantation corrects renal insufficiency and most metabolic abnormalities but hyperparathyroidism persists in 50% of children after transplantation. The aim of this study was to investigate parathyroid hormone (PTH) course and potential risk factors for hyperparathyroidism in children after renal transplant. We collected data from 145 transplanted children (mean follow-up 4.7 years). Intact PTH level (iPTH) rapidly decreased in the first 6 months post-transplant and continued to decline in the following years. iPTH was above the normal range in 69.1% of the patients at the time of transplant and in 47% 1 year later, this improvement continuing thereafter. Hypercalcemia was present in 20.3% of the patients before transplant and in 6.3 and 4.1% of patients 6 months and 1 year after transplant, respectively. Hypophosphatemia was present in 5.5% of the patients at 6 months, and 45.5% of the patients needed phosphorus supplements during the first 6 months after transplant. Multivariate analysis indicated pre-transplant hyperparathyroidism, dialysis duration, creatinine clearance and hypophosphatemia as predictors of persistent hyperparathyroidism. In kidney transplanted children, serum iPTH normalized in the long term in the majority of cases. Thus, parathyroidectomy should be reserved for selected patients.

[Renal biopsy collection (2000-2008) from a single center, the Policlinico Umberto I, Sapienza University, Rome]. / Casistica delle biopsie renali della Sapienza Universita' di Roma - Azienda Policlinico Umberto I: frequenza delle malattie renali biopticamente accertate negli anni 2000-2008.

The collection of data about renal biopsies is an important starting point for clinical and epidemiological studies about kidney disease. The aim of this study was the evaluation of the frequency of the different kidney diseases, their clinical presentation and the demographic features of the population based on renal biopsies performed at our center during the years 2000-2008. Clinical presentations were defined as nephrotic syndrome (NS), urinary abnormalities, macroscopic hematuria, acute renal failure (ARF) and chronic renal failure (CRF). Kidney diseases were divided into five groups: 1) primary glomerulonephritis; 2) secondary glomerulonephritis; 3) tubulointerstitial nephritis (TIN); 4) vascular-disease-associated kidney disease; 5) miscellaneous. Primary glomerulonephritis was the most common (58.64%), followed by secondary glomerulonephritis (27.03%); TIN and vascular diseases were diagnosed in 1.46% and 7.78% of cases, respectively. The most common indications to perform renal biopsies were urinary abnormalities in 45.01% of cases, followed by CRF (21.51%) and NS (21.37%); macroscopic hematuria (6.41%) and ARF (5.70%) were less common. The most common kidney disease in men was IgA nephropathy (27.91%), while lupus nephritis was the most common in women (18.88%). In patients older than 65 years of age membranous glomerulonephritis (34.67%) was the most common kidney disease. The availability of these data is useful to assess the distribution and clinical presentation of kidney diseases among patients hospitalized at the Policlinico Umberto I in Rome.

Radiotherapy-induced hyperthyroidism in a cystinotic kidney transplant patient with Hodgkin lymphoma.

Hypothyroidism is a well-known complication of cystinosis. PTLD incidence in pediatric renal transplant population ranges between 1 and 4.5%. We describe the case of a young cystinotic patient who developed hyperthyroidism after radiotherapy for Hodgkin lymphoma. He is a 23-yr-old male who was diagnosed with cystinosis at the age of two. He developed renal failure and other extrarenal complications but never presented hypothyroidism. At the age of 12, he received a successful kidney transplant from a cadaveric donor. Two yr later, EBV-positive Hodgkin lymphoma was diagnosed and chemotherapy and radiotherapy were administered. He achieved remission. Eight yr later, autoimmune hyperthyroidism secondary to previous radiation was detected, and he slowly became symptomatic. Clinical symptoms and laboratory data spontaneously normalized. This is the first case of a cystinotic patient developing hyperthyroidism. Thyroid disorders, especially hypothyroidism, have been reported in association with neck irradiation. Hypothyroidism would have been considered to be a late complication of cystinosis and not a consequence of radiotherapy. Thyroid hormones, clinical examination, and history evaluation for thyroid dysfunction should be periodically monitored after neck radiotherapy. The thyroid should always be excluded from the irradiation fields. Multidisciplinary interaction in difficult cases should be encouraged.

Serum creatinine levels are significantly influenced by renal size in the normal pediatric population.

BACKGROUND AND OBJECTIVES: Clinical and experimental data have shown that differences in nephron endowment result in differences in renal mass and predisposition to chronic renal failure, hypertension, and proteinuria. We hypothesized that a significant proportion of the variance in GFR, as estimated by serum creatinine, is attributable to differences in renal size in normal children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 1748 normal renal ultrasounds that were performed in children older than 6 months were reviewed. For each ultrasound, serum creatinine, serum blood urea nitrogen, and systolic and diastolic office BP were recorded. Renal size was evaluated as a function of renal length and thickness. All data were normalized for height, weight, age, and gender. RESULTS: When expressed as SD scores, a significant correlation was found between kidney size and serum creatinine (P < 0.0001) and between kidney size and serum blood urea nitrogen (P < 0.002). When dividing kidney size data per quintiles, a difference of 0.51 SD score in serum creatinine was observed between the lowest and highest quintile. No significant correlation was found with office BP measurements. CONCLUSIONS: These data show that, even in the normal pediatric population, differences in renal function are significantly explained by differences in renal mass. Methodologic limitations of this study are likely to underestimate this relationship.

Long-term cardiovascular effects of pre-transplant native kidney nephrectomy in children.

Left ventricular (LV) hypertrophy (H) and hypertension are prevalent in children with end-stage renal disease (ESRD) and after renal transplantation. Severe hypertension prior to renal transplantation has traditionally been an indication for native kidney nephrectomy. The impact of nephrectomy on cardiovascular disease has not been well documented. We retrospectively evaluated echocardiographic and ambulatory blood pressure monitoring (ABPM) data in 67 young adults who had undergone transplantation in the pediatric age with a mean follow-up of 10.4 years. Unilateral or bilateral nephrectomies had been performed in 32 patients. The number of antihypertensive drugs used prior to transplantation was significantly higher in the nephrectomized groups. At follow-up the amount of antihypertensive medications was similar between groups and no significant differences were observed in mean arterial blood pressure (MAP) or LV mass index (LVMi). LVH was observed in 50% of non-nephrectomized patients, 45.4% of patients with unilateral nephrectomy, and 44.4% of patients without native kidneys (p = n.s.). In conclusion, unilateral or bilateral nephrectomies prior to transplantation do not appear to influence blood pressure control or the prevalence of LVH after renal transplantation. Longitudinal studies with repeated assessment of LVMi, before and after renal transplantation, are needed to assess the impact of residual activity of native kidneys on arterial blood pressure and cardiac structural changes, even in normotensive patients, to evaluate cardiovascular morbidity.

Cyclosporine A treatment in patients with Alport syndrome: a single-center experience.

Limited and discordant data are available on cyclosporine A (CsA) treatment for proteinuria in Alport syndrome (AS). To address this lack of consistent data, we have studied 15 AS patients (14 males; mean age 15.3 +/- 6.0 years) treated with CsA. Patient selection criteria included a urinary protein/creatinine ratio > or =1 mg/mg and a creatinine clearance >40 ml/min/1.73 m(2). CsA treatment was started at an initial dose of 5 mg/kg/day and subsequently adjusted to reach target C2 levels of 500 ng/ml. Renal function, proteinuria, and blood pressure were monitored. Blood pressure was treated to avoid the administration of angiotensin converting enzyme or angiotensin receptor blockers for the first 2 years of therapy. The average follow-up was 3.5 years. Five patients had chronic renal failure at the beginning of treatment, of whom three and one reached end-stage renal failure within 1 and 3 years, respectively. In the remaining 11 patients, the glomerular filtration rate declined by 11 +/- 6% within 6 months, but remained stable thereafter. Proteinuria decreased by 63 +/- 21% from baseline, but returned nearly to baseline after 2.5 years of follow-up. Based on these results, we suggest that CsA is effective in reducing proteinuria in patients with Alport syndrome but that this effect is temporary. Our data do not support the use of CsA therapy for proteinuric patients with AS, particularly if they have chronic renal failure.

Serum leptin in dialysis renal osteodystrophy.

BACKGROUND: The hormone leptin is considered to have a role in the prevention of osteoporosis and probably acts on bone tissue through inhibition of osteoclasia. Its action has been attributed to interference in osteoprotegerin (OPG)/OPG-ligand equilibrium. Contradictory data also have been reported, casting doubts on the positive effect on bone mass of the hormone, at least in males. To date, the relation between serum leptin levels of dialysis patients and renal osteodystrophy, defined by histomorphometric and histodynamic parameters of bone, has not been studied. METHODS: The study included 46 hemodialysis patients (32 men, 14 women; age, 57.2 +/- 11.4 years). A transiliac bone biopsy after double-tetracycline labeling was performed for histological, histomorphometric, and histodynamic studies. Blood samples were drawn for leptin, intact parathyroid hormone (PTH), whole PTH (PTH1-84), OPG, bone alkaline phosphatase, calcium, phosphate, 25-hydroxycholecalciferol, and calcitriol. Serum leptin was measured by means of a radioimmunoassay. RESULTS: Eighteen patients had mixed osteodystrophy (MO); 17 patients, hyperparathyroidism; 9 patients, adynamic bone disease (ABD); and 2 patients, osteomalacia. Aluminum histochemistry results were positive in 1 patient with ABD and 1 patient with MO. A sex difference was found in serum leptin levels (48.9 +/- 38 ng/mL in women and 12.2 +/- 13.2 ng/mL in men; P < 0.0002). In the entire population, lnleptin correlated significantly with body mass index (BMI; P < 0.01). SD score (SDS) leptin (adjusted for BMI, sex, and age) correlated inversely with PTH1-84 level and osteoclastic surface (OcS/BS; P < 0.05) and had a borderline correlation with bone formation rate. Correlations between leptin levels and other parameters were enhanced in men. SDS leptin correlated inversely with OcS/BS (P < 0.01), osteoclastic number (P < 0.01), and mineral apposition rate (P < 0.01). In addition, SDS leptin had a borderline inverse correlation with osteoblast surface (P < 0.06) and significant correlation with OPG level (P < 0.05). No difference was found in serum leptin levels between histological groups. CONCLUSION: The reported data confirm the finding of a positive relation between serum leptin level and BMI and greater levels in women compared with men. Serum leptin level is connected to bone resorption and also bone formation, both inversely related to serum leptin levels. The decrease in osteoclasia that accompanies increasing serum leptin levels does not seem to be related to an enhanced OPG effect because it was accompanied by decreased OPG levels. Low-turnover bone disease does not appear to be caused by increased serum leptin levels. The nature of the interrelation between serum leptin and PTH1-84 levels requires further study.