Massimiliano Barsotti

Secondary Hyperparathyroidism in Severe Chronic Renal Failure Is Corrected by Very-Low Dietary Phosphate Intake and Calcium Carbonate Supplementation

The main purpose of our study was to verify the effect of a very-low-protein, low-phosphorus diet, supplemented with essential amino acids and keto analogues and with calcium carbonate, on circulating levels of intact parathyroid hormone (i-PTH) in severe chronic renal failure patients with secondary hyperparathyroidism, not treated with any vitamin D preparation. To this aim, we shifted 21 chronic uremics (12 males, 9 females; age 56 ± 13 years) with serum creatinine >6.5 mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5 mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium keto analogues (Ketodiet), calcium carbonate (2–4 g/day), iron, and vitamin B12 preparations. The energy supply of both diets was 30–35 kcal/kg/day. Exclusion criteria were a poor compliance with dietary or supplement prescriptions or signs of autonomic hyperparathyroidism. After 4 ± 2 months of Ketodiet, the i-PTH serum levels decreased by 49% as a mean (from 441 ± 233 to 225 ± 161 pg/ml, p < 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum calcium increased. The great reduction of serum and urinary urea demonstrated a good compliance with Ketodiet, and no sign of protein malnutrition was observed. These findings confirm that even in severe chronic uremic patients dietary phosphorus restriction and calcium carbonate supplementation lower i-PTH serum levels. This is one of the goals of the dietary treatment that can be safely achieved, provided good compliance both with the dietary prescriptions and with adequate energy and supplement intakes.

Effects of Oral Administration of Heparan Sulphate in the Rat Remnant Kidney Model

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 ± 22 vs. 80 ± 54 mg/24 h , p < 0.01), lower urea plasma levels (75 ± 34 vs. 134 ± 105 mg/dl, p < 0.01) and higher creatinine clearance (66 ± 15 vs. 47 ± 21 ml/min · 102, p < 0.05) than control rats. Remnant kidney weight (2.3 ± 1.1 vs. 1.3 ± 0.2 g, p < 0.01) and heart weight (1.3 ± 0.2 vs. 1.1 ± 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 ± 19 vs. 115 ± 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.

Presurgical Setting of Secondary Hyperparathyroidism Using High-Resolution Sonography and Color Doppler.

PURPOSE High-resolution sonography (US) with color Doppler imaging (CDI) is a simple, noninvasive, safe and repeatable technique able to highlight the presence of hyperplastic parathyroid glands and changes in their volume, structure, and vascularization during uremia. The primary aim of this study was to assess the diagnostic accuracy of US and the sensitivity for localizing parathyroid glands with a volume ≥ 500 mm(3). The secondary aim was to assess the parameters that define parathyroid glandular perfusion. MATERIALS AND METHODS The diagnostic use of US was assessed in 40 consecutive uremic patients with severe secondary hyperparathyroidism (sHPT) who were receiving maintenance hemodialysis or conservative therapy with a hypoproteic-hypophosphoric diet and had undergone parathyroidectomy. Prior to surgery (99m)TC-sestamibi scintigraphy (SM) was performed in all patients. RESULTS The sensitivity, specificity, positive predictive value and accuracy of US were 74 %, 75 %, 98 %, and 74 %, respectively. The sensitivity for localizing glands with a volume ≥ 500 mm(3) was 90 %. US and SM had a combined sensitivity of 83 %. The vascularization of parathyroid glands became more evident with increasing glandular volume. With CDI, the signs of hypervascularization (i. e. an enlarged feeding artery at the hilum, a peripheral arc of vascularity and/or ray-like endonodular vessels) were present in 77 % of glands with a volume ≥ 500 mm(3). CONCLUSION The sensitivity of US is higher than that of SM, but it cannot be compared with that of parathyroidectomy (74 vs. 95 %). However, US/CDI is able to characterize glands with different volumes and vascular patterns. Since glandular volume and vascularization are indicative of the severity of sHPT, this study suggests that the main role of US/CDI in the setting of sHPT should be to complete the diagnosis and to evaluate the morphological changes of enlarged glands during uremia in order to define surgical timing, rather than to assess the presurgical location of glands.

Efficacy and safety of basiliximab in kidney transplantation

The efficacy and safety of basiliximab, in combination with different maintenance regimens, are extensively addressed in the available literature. Basiliximab reduces the incidence of acute rejection, allows a safe reduction of steroid dosage, and is associated with economic savings, although there is substantially no proof that basiliximab prolongs either patient or graft survival. Initial basiliximab administration entails a low-risk and is associated with fewer adverse events than T cell depleting agents. However, life-threatening reactions were reported following re-exposure to basiliximab in recipients who lost graft function early after transplantation and, therefore, discontin-ued all immunosuppressive agents.

The grafted kidney takes over: disappearance of the nephrotic syndrome after preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.

Amelioration of Cardiac Morphology and Function in Type 1 Diabetic Patients With Sustained Success of Pancreas Transplant Alone

Pancreas transplant alone (PTA) is coming of age for the treatment of selected type 1 diabetic (T1D) patients (1). By restoring endogenous insulin secretion, it eliminates acute diabetes complications and may improve late microvascular complications (1,2). However, the impact of PTA on the recipient’s heart is largely unknown. Here, we report that successful PTA is associated with long-term amelioration of cardiac morphology and function. As of December 2013, 93 PTAs have been performed in our center, with 5-year patient and pancreas survival of 97 and 76%, respectively (2). Indications and contraindications for PTA, surgery, and immunosuppression were as previously reported (1,2). From this cohort, 30 consecutive successfully transplanted patients (males 50%; age 38 ± 8 years; BMI 24.0 ± 2.8 kg/m2; diabetes duration 25 ± 9 years; insulin dose 47 ± …

Metabolic and cardiovascular effects of beta cell replacement in type 1 diabetes

Type 1 diabetes is associated with high morbidity and mortality, mostly due to the acute and chronic complications of the disease. Restoration of the lost beta cell mass by pancreas transplantation is the treatment of choice in selected type 1 diabetic patients. Growing data show that successful pancreas transplantation normalizes the metabolic alterations of diabetes, and can slow the progression, stabilize, and even favor the regression of secondary complications of the disease, including those at the cardiovascular level.

Sacral neuromodulation enabling simultaneous pancreas and kidney transplantation: a first case

We report a case where simultaneous pancreas and kidney transplantation was precluded because of recurrent urinary tract infections due to non-obstructive chronic urinary retention requiring clean intermittent self catheterisation in a diabetic woman with end stage renal disease. Sacral neuromodulation restored voiding and cured recurrent urinary tract infections, enabling her to undergo simultaneous pancreas and kidney transplantation.

Novel treatment (new drug/intervention; established drug/procedure in new situation): Sacral neuromodulation enabling simultaneous pancreas and kidney transplantation: a first case

We report a case where simultaneous pancreas and kidney transplantation was precluded because of recurrent urinary tract infections due to non-obstructive chronic urinary retention requiring clean intermittent self catheterisation in a diabetic woman with end stage renal disease. Sacral neuromodulation restored voiding and cured recurrent urinary tract infections, enabling her to undergo simultaneous pancreas and kidney transplantation.

Circulating Levels of IGF-I in Patients with Chronic Uremia on Conservative Dietary Treatment

The assessment of nutritional status is a very important step in the clinical management of chronic uremic patients, because of the influences of chronic renal failure and of dietary manipulations on the energy and protein metabolism. In this study some serum biochemical markers of protein nutrition, including IGF-I and pre-albumin, have been measured in chronic renal failure patients treated with two different low-protein diets, according to the residual renal function for several months. Our results showed no significant changes of IGF-I, pre-albumin or albumin serum levels in the patients treated with a very low-protein diet (0.3 g/Kg b.w. per day) supplemented with essential amino acids and ketoacids, in comparison with the patients on a conventional low-protein (0.6 g/Kg b.w. per day) diet.