Growth hormone therapy in HHRH.

Background: Hereditary Hypophosphatemic Rickets with Hypercalciuria (HHRH) (SLC34A3 gene, OMIM 241530) is an autosomal recessive disorder that results in a loss of function of the sodium-phosphate NPT2c channel at the proximal tubule. Phosphate supplementation rarely improves serum phosphate, hypercalciuria, nephrocalcinosis, 1,25(OH)2 vitamin D (1,25(OH)2D) levels or short stature. Methods: We describe 23Na MRI and the successful use of recombinant human growth hormone (rhGH) and Fluconazole to improve growth (possibly confounded by puberty) and hypercalciuria in a now 12-year-old male with HHRH (novel homozygous SLC34A3 mutation, c.835_846 + 10del.T). Results: The patient had chronic bone pain, hypophosphatemia (0.65 mmol/L[reference interval 1.1-1.9]), pathological fractures and medullary nephrocalcinosis/hypercalciuria (urinary calcium/creatinine ratio 1.66 mol/mmol[<0.6]). TmP/GFR was 0.65 mmol/L[0.97-1.64]; 1,25(OH)2D was >480 pmol/L[60-208]. Rickets Severity Score was 4. Treatment with 65 mg/kg/day of sodium phosphate and potassium citrate 10 mmol TID failed to correct the abnormalities.Adding rhGH at 0.35 mg/kg/week to the phosphate therapy, improved bone pain, height z-score from -2.09 to -1.42 over 6 months, without a sustained effect on TmP/GFR. Fluconazole was titrated to 100 mg once daily, resulting for the first time in a reduction of the 1,25(OH)2D to 462 and 426 pmol/L; serum phosphate 0.87 mmol/L, and calcium/creatinine ratio of 0.73.23Na MRI showed normal skin (z-score + 0.68) and triceps surae muscle (z-score + 1.5) Na+ levels; despite a defect in a sodium transporter, hence providing a rationale for a low sodium diet to improve hypercalciuria. Conclusions: The addition of rhGH, Fluconazole and salt restriction to phosphate/potassium supplementation improved the conventional therapy. Larger studies are needed to confirm our findings.

Renal transplants from older deceased donors: Is pre-implantation biopsy useful? A monocentric observational clinical study.

AIM: To compare survival of kidney transplants from deceased extended criteria donors (ECD) according to: (1) donor graft histological score; and (2) allocation of high score grafts either to single (SKT) or dual (DKT) transplant. METHODS: Renal biopsy was performed as part of either a newly adopted DKT protocol, or of surveillance protocol in the past. A total 185 ECD graft recipients were categorized according to pre-implantation graft biopsy into 3 groups: SKT with graft score 1 to 4 [SKT(1-4), n = 102]; SKT with donor graft score 5 to 8 [SKT(> 4), n = 30]; DKT with donor graft score 5 to 7 (DKT, n = 53). Graft and patient survival were analyzed by Kaplan-Meier curves and compared by log-rank test. Mean number of functioning graft years by transplant reference, and mean number of dialysis-free life years by donor reference in recipients were also calculated at 1, 3 and 6 years from transplantation. RESULTS: There were no statistically significant differences in graft and patient survival between SKT(1-4) and SKT(> 4), and between SKT(> 4) and DKT. Recipient renal function (plasma creatinine and creatinine clearance) at 1 years did not differ in SKT(1-4) and SKT(> 4) (plasma creatinine 1.71 ± 0.69 and 1.69 ± 0.63 mg/dL; creatinine clearance 49.6 + 18.5 and 52.6 + 18.8 mL/min, respectively); DKT showed statistically lower plasma creatinine (1.46 ± 0.57, P < 0.04) but not different creatinine clearance (55.4 + 20.4). Due to older donor age in the DKT group, comparisons were repeated in transplants from donors older than 70 years, and equal graft and patient survival in SKT and DKT were confirmed. Total mean number of functioning graft years by transplant reference at 1, 3 and 6 post-transplant years were equal between the groups, but mean number of dialysis-free life years by donor reference were significantly higher in SKT (mean difference compared to DKT at 6 years: 292 [IQR 260-318] years/100 donors in SKT(1-4) and 292.5 [(IQR 247.8-331.6) in SKT(> 4)]. CONCLUSION: In transplants from clinically suitable ECD donors, graft survival was similar irrespective of pre-implantation biopsy score and of allocation to SKT or DKT. These results suggest use of caution in the use of histology as the only decision criteria for ECD organ allocation.

Why Is Your Patient Still Short of Breath? Understanding the Complex Pathophysiology of Dyspnea in Chronic Kidney Disease.

Dyspnea is one of the most common symptoms associated with CKD. It has a profound influence on the quality of life of CKD patients, and its underlying causes are often associated with a negative prognosis. However, its pathophysiology is poorly understood. While hemodialysis may address fluid overload, it often does not significantly improve breathlessness, suggesting multiple and co-existing alternative issues exist. The aim of this article is to discuss the main pathophysiologic mechanisms and the most important putative etiologies underlying dyspnea in CKD patients. Congestive heart failure, unrecognized chronic lung disease, pulmonary hypertension, lung fibrosis, air microembolism, dialyzer bio-incompatibility, anemia, sodium, and fluid overload are potential frequent causes of breathing disorders in this population. However, the relative contributions in any one given patient are poorly understood. Systemic inflammation is a common theme and contributes to the development of endothelial dysfunction, lung fibrosis, anemia, malnutrition, and muscle wasting. The introduction of novel multimodal imaging techniques, including pulmonary functional magnetic resonance imaging with inhaled contrast agents, could provide new insights into the pathophysiology of dyspnea in CKD patients and ultimately contribute to improving our clinical management of this symptom.

The role of blood pressure, body weight and fat distribution on left ventricular mass, diastolic function and cardiac geometry in children.

BACKGROUND: Hypertension and obesity in childhood are related to early cardiac damage, as left ventricular hypertrophy. Few studies have analyzed the independent effects of hypertension and weight excess on diastolic function and left ventricular geometry. OBJECTIVE: We studied the effects of weight, waist circumference (as an index of fat distribution) and blood pressure on left ventricular mass index, the risk of left ventricular hypertrophy, diastolic function and left ventricular geometry in 526 children (237 girls, age range 6-15 years). METHODS: Children were divided into normotensive, prehypertensive and hypertensive (US Nomograms) groups, and into normal-weight, overweight, and obese (International Obesity Task Force classification) groups. Left ventricular mass index, diastolic function and left ventricular geometry were assessed. RESULTS: SBP z-scores and blood pressure categories significantly influenced cardiac mass (P < 0.001 and P = 0.02, respectively) and the prevalence of left ventricular hypertrophy (P < 0.001 and P < 0.05, respectively). Obesity, BMI, and waist circumference z-scores were significantly associated with an increment in E/Em ratio (P < 0.001, P < 0.01, and P < 0.01, respectively). Increasing blood pressure values and the presence of prehypertension (P < 0.05) and hypertension (P < 0.003), but not weight excess, were associated with concentric cardiac remodeling. In contrast, concentric hypertrophy was associated with hypertension (P < 0.01), obesity (P < 0.001), and increasing waist circumference (P < 001). CONCLUSIONS: Blood pressure values and hypertension are independently associated with an increase of cardiac mass and the presence of cardiac hypertrophy. Obesity and waist circumference, but not hypertension, are associated with a worsening of diastolic function, whereas only hypertensive children show high prevalence of concentric remodeling. Blood pressure and body weight and fat distribution have an independent and different impact on left ventricular structure and function in children.