Treating Type 1 Diabetes by Pancreas Transplant Alone: A Cohort Study on Actual Long-term (10 Years) Efficacy and Safety.

BACKGROUND: Physiologically regulated insulin secretion and euglycemia are achievable in type 1 diabetes (T1D) by islet or pancreas transplantation. However, pancreas transplant alone (PTA) remains a debated approach, with uncertainties on its relative benefits and risks. We determined the actual long-term (10 y) efficacy and safety of PTA in carefully characterized T1D subjects. METHODS: This is a single-center, cohort study in 66 consecutive T1D subjects who received a PTA between April 2001 and December 2007, and were then all followed until 10 y since transplant. Main features evaluated were patient survival, pancreas graft function, C-peptide levels, glycemic parameters, and the function of the native kidneys. RESULTS: Ten-year actual patient survival was 92.4%. Optimal (insulin independence) or good (minimal insulin requirement) graft function was observed in 57.4% and 3.2% of patients, respectively. Six (9.0%) patients developed stage 5 or 4 chronic kidney disease. In the remaining individuals bearing a successful PTA, estimated glomerular filtration rate (eGFR) decline per year was -2.29 ± 2.69 mL/min/1.73 m2. Reduction of eGFR at 1 y post-PTA was higher in those with pre-PTA hyperfiltration and higher HbA1c concentrations; eGFR changes afterward significantly correlated with diabetes duration. In recipients with normoglycemia at 10 y, 74% of normoalbuminuric or microalbuminuric subjects pre-PTA remained stable, and 26% progressed toward a worse stage; conversely, in 62.5% of the macroalbuminuric individuals albuminuria severity regressed. CONCLUSIONS: These long-term effects of PTA on patient survival, graft function, and the native kidneys support PTA as a suitable approach to treat diabetes in selected T1D patients.

Nutritional Aspects in Diabetic CKD Patients on Tertiary Care.

Background and objectives: Diabetes is largely prevalent in the chronic kidney disease (CKD) population. Both conditions have metabolic and nutritional abnormalities that affect body composition and the presence of diabetes makes the dietary management of CKD patients more difficult. The aim of this study was to assess peculiar nutritional and functional aspects of diabetic patients in an adult/elderly CKD population, and their predictive significance. Materials and methods: This prospective cohort study included 144 out-patients aged >55 years, affected by stage 3b-4 CKD, on tertiary care clinic; 48 (40 males) were type 2 diabetics and 96 (80 males) were nondiabetics. The two groups have similar age, gender, and residual renal function (30 ± 9 vs. 31 ± 11 mL/min×1.73). All patients underwent a comprehensive nutritional and functional assessment and were followed for 31 ± 14 months. Results: Diabetic CKD patients showed higher waist circumference and fat body mass, lower muscle mass, and lower number of steps per day and average daily METs. Meanwhile, resting energy expenditure (REE), as assessed by indirect calorimetry, and dietary energy intake were similar as well as hand-grip and 6 min walking test. Diabetic patients did not show a greater risk for all-cause mortality and renal death with respect to nondiabetics. Middle arm muscle circumference, phase angle, serum cholesterol, and serum albumin were negatively related to the risk of mortality and renal death after adjustment for eGFR. Conclusions: CKD diabetic patients differed from nondiabetics for a greater fat mass, lower muscle mass, and lower physical activity levels. This occurred at the same REE and dietary energy intake. The outcome of diabetic or nondiabetic CKD patients on tertiary care management was similar in terms of risk for mortality or renal death. Given the same residual renal function, low levels of muscle mass, phase angle, serum albumin, and cholesterol were predictive of poor outcome. Overall, a malnutrition phenotype represents a major predictor of poor outcome in diabetic and nondiabetic CKD patients.

Which Diet for Calcium Stone Patients: A Real-World Approach to Preventive Care.

Kidney stone disease should be viewed as a systemic disorder, associated with or predictive of hypertension, insulin resistance, chronic kidney disease and cardiovascular damage. Dietary and lifestyle changes represent an important strategy for the prevention of kidney stone recurrences and cardiovascular damage. A full screening of risk factors for kidney stones and for cardiovascular damage should be recommended in all cases of calcium kidney stone disease, yet it is rarely performed outside of stone specialist clinics. Many patients have a history of kidney stone disease while lacking a satisfactory metabolic profile. Nonetheless, in a real-world clinical practice a rational management of kidney stone patients is still possible. Different scenarios, with different types of dietary approaches based on diagnosis accuracy level can be envisaged. The aim of this review is to give patient-tailored dietary suggestions whatever the level of clinical and biochemistry evaluation. This can help to deliver a useful recommendation, while avoiding excessive dietary restrictions especially when they are not based on a specific diagnosis, and therefore potentially useless or even harmful. We focused our attention on calcium stones and the different scenarios we may find in the daily clinical practice, including the case of patients who reported renal colic episodes and/or passed stones with no information on stone composition, urinary risk factors or metabolic cardiovascular risk factors; or the case of patients with partial and incomplete information; or the case of patients with full information on stone composition, urinary risk factors and metabolic cardiovascular profile.

Prevalence and Correlates of Sarcopenia among Elderly CKD Outpatients on Tertiary Care.

BACKGROUND: Sarcopenia is a widespread concern in chronic kidney disease (CKD) as well in elderly patients and is one of the main reasons why low-protein diets for this population are controversial. The aim of this study was to assess the prevalence and correlates of sarcopenia among elderly male patients affected by CKD followed up in an outpatient nephrology clinic, where moderate protein restriction (0.6⁻0.8 g/Kg/day) is routinely recommended to patients in CKD stage 3b-5 not on dialysis. METHODS: This observational study included 80 clinically-stable male out-patients aged >60, affected by stage 3b-4 CKD. Forty patients aged ≥75 (older seniors) were compared to the other forty patients aged 60⁻74 (younger seniors). All patients underwent a comprehensive nutritional and functional assessment. RESULTS: Older seniors showed lower serum albumin, hand-grip strength, body mass index (BMI), skeletal muscle mass, and resting energy expenditure. Protein intake was significantly lower in older seniors whereas energy intake was similar. Average daily physical activity was lower in the older seniors than in the younger ones. Sarcopenia was more prevalent in older than in younger seniors. Among older seniors, sarcopenic and non-sarcopenic ones differed in age and performance on the Six-Minute Walk test, whereas the estimated glomerular filtration rate (eGFR), biochemistry, dietary protein, and energy intakes were similar. CONCLUSIONS: Older senior CKD male patients have lower muscle mass, muscle strength, and physical capacity and activity levels, with a higher prevalence of sarcopenia than younger patients. This occurs at the same residual renal function and metabolic profile and protein intake. Energy intake was at the target in both subgroups. In this CKD cohort, sarcopenia was associated with age and physical capacity, but not with eGFR or dietary intakes.

Nutritional support in the tertiary care of patients affected by chronic renal insufficiency: report of a step-wise, personalized, pragmatic approach.

BACKGROUND: Dietary treatment is helpful in CKD patients, but nutritional interventions are scarcely implemented. The main concern of the renal diets is its feasibility with regards to daily clinical practice especially in the elderly and co-morbid patients. This study aimed to evaluate the effects of a pragmatic, step-wise, personalized nutritional support in the management of CKD patients on tertiary care. METHODS: This is a case-control study. It included 823 prevalent out-patients affected by CKD stage 3b to 5 not-in-dialysis, followed by tertiary care in nephrology clinics; 305 patients (190 males, aged 70 ± 12 years) received nutritional support (nutritional treatment Group, NTG); 518 patients (281 males, aged 73 ± 13 years) who did not receive any dietary therapy, formed the control group (CG). In the NTG patients the dietary interventions were assigned in order to prevent or correct abnormalities and to maintain a good nutritional status. They included manipulation of sodium, phosphate, energy and protein dietary intakes while paying special attention to each patient's dietary habits. RESULTS: Phosphate and BUN levels were lower in the NTG than in the CG, especially in stage 4 and 5. The prevalence of hyperphosphatemia was lower in the NTG than in CG in stage 5 (13.3 % vs 53.3 %, p < 001, respectively), in stage 4 (4.1 % vs 18.3 % vs, p < 0.001) and stage 3b (2.8 % vs 9.5 % p < 0.05). Serum albumin was higher in NTG than in CG especially in stage 5 . The use of calcium-free intestinal phosphate binders was significantly lower in NTG than in CG (11 % vs 19 % p < 0.01), as well as that of Erythropoiesis stimulating agents (11 % vs 19 %, p < 0.01), and active Vitamin D preparations (13 % vs 21 %, p < 0.01). CONCLUSIONS: This case-control study shows the usefulness of a nutritional support in addition to the pharmacological good practice in CKD patients on tertiary care. Lower phosphate and BUN levels are obtained together with maintenance of serum albumin levels. In addition, a lower need of erythropoiesis stimulating agents, phosphate binders and active Vitamin D preparations was detected in NTG. This study suggests that a nutritional support may be useful in the management of the world-wide growing CKD burden.

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.

Transplantation of the pancreas.

Pancreas transplantation consistently induces insulin-independence in beta-cell-penic diabetic patients, but at the cost of major surgery and life-long immunosuppression. One year after grafting, patient survival rate now exceeds 95 % across recipient categories, while insulin independence is maintained in some 85 % of simultaneous pancreas and kidney recipients and in nearly 80 % of solitary pancreas transplant recipients. The half-life of the pancreas graft currently averages 16.7 years, being the longest among extrarenal grafts, and substantially matching the one of renal grafts from deceased donors. The difference between expected (100 %) and actual insulin-independence rate is mostly explained by technical failure in the postoperative phase, and rejection in the long-term period. Death with a functioning graft remains a further major issue, especially in uremic patients who have undergone prolonged periods of dialysis. Refinements in graft preservation, surgical techniques, immunosuppression, and prophylactic treatments are expected to further improve the results of pancreas transplantation.

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.

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, discontinued 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.

Effect of heparan sulphate on kidney tissue expression of TGF-beta, rhoA, laminin and fibronectin in subtotally nephrectomized rats.

BACKGROUND: Different mitogens are involved in the pathogenesis of kidney damage after subtotal nephrectomy. One of them, TGF-beta, controls mesangial cell proliferation and interstitial fibrosclerosis. The transduction of the TGF-beta signal is controlled by intracellular signalling molecules such as Ras G monomeric proteins. Renal damage after subtotal nephrectomy (5/6 Nx) can be prevented by heparins, but so far no immunohistochemical correlation between TGF-beta, TGF-beta induced matrix molecules and Rho proteins has been investigated. Since the Ras transduction pathway has recently been associated with progression of renal damage, we evaluated the effect of heparan sulphate (HS) on the expression of TGF-beta, laminin, fibronectin and a Ras protein, RhoA, in the rat remnant kidney model. METHODS: The immunoperoxidase technique was employed to reveal the antigens on 18 remnant kidneys from 5/6 nephrectomized rats, nine untreated and nine treated with oral HS, and on seven normal kidneys from sham-operated rats. Data were semiquantitatively analyzed by an image analyzer (Quantimet, Leica). RESULTS: The expression of the antigens was significantly higher in the remnant kidneys than in normals. The high TGF-beta, laminin, fibronectin and RhoA expression observed in subtotally nephrectomized rats suggests a role for these molecules in the pathogenesis of progressive renal damage. However, apart from RhoA, HS-treated rats had significantly lower levels of the antigens than the untreated rats. CONCLUSIONS: HS treatment is associated with significantly lower renal expression of TGF-beta, laminin and fibronectin, but not of RhoA. This suggests that the renal-protective effect of HS may be obtained by modulating the TGF-beta pathway, independently of RhoA-mediated transduction.

Vegetarian diet alternated with conventional low-protein diet for patients with chronic renal failure.

OBJECTIVES: A dietary management program, consisting of the alternation between a vegetarian low-protein diet (VD) and an animal-based conventional low-protein diet (CLPD), aims to increase foods choices and to improve compliance with dietary prescriptions, psychologic aspects, and the quality of life of renal patients. The present study investigates the subjective effects and the practical consequences of this dietary approach in patients with chronic renal failure. METHODS: Twenty patients (13 men, 7 women, 53 +/- 10 years) with chronic renal failure (creatinine clearance, <45 mL/min) were given the possibility to alternate (at their own convenience) the CLPD with the VD. After a follow-up period of 9 +/- 8 months, biochemistries were drawn and a questionnaire was mailed to asses the patients' subjective remarks about the proposed dietary management. RESULTS: Most of the patients (90%) favorably accepted this dietary schedule because it provided more variety, it was less repetitive, and it was more suitable for those leading an active life. In many cases, patients reported that their quality of life and some psychologic problems were improved, as well as the palatability of the diet. On this dietary regimen, monthly demands of starch-made foods can be reduced and, hence, the social and/or individual costs. These features contributed to better compliance with dietary prescriptions. Nutritional parameters did not change significantly, and a decrease in total and low-density lipoprotein cholesterol levels were observed. CONCLUSIONS: Our observations suggest that alternating between an animal-based CLPD and a vegetable-based VD can provide a useful dietary management for renal patients, giving them more chances for long-lasting dietary compliance.