Alberto Jeantet

Low-protein vegetarian diet with alpha-chetoanalogues prior to pre-emptive pancreas-kidney transplantation.

BACKGROUND Pre-emptive pancreas-kidney transplantation is increasingly considered the best therapy for irreversible chronic kidney disease (CKD) in type 1 diabetics. However, the best approach in the wait for transplantation has not yet been defined. AIM To evaluate our experience with a low-protein (0.6 g/kg/day) vegetarian diet supplemented with alpha-chetoanalogues in type 1 diabetic patients in the wait for pancreas-kidney transplantation. METHODS Prospective study. Information on the progression of renal disease, compliance, metabolic control, reasons for choice and for drop-out were recorded prospectively; the data for the subset of patients who underwent the diet while awaiting a pancreas-kidney graft are analysed in this report. RESULTS From November 1998 to April 2004, 9 type 1 diabetic patients, wait-listed or performing tests for wait-listing for pancreas-kidney transplantation, started the diet. All of them were followed by nephrologists and diabetologists, in the context of integrated care. There were 4 males and 5 females; median age 38 years (range 27.9-45.5); median diabetes duration 23.8 years (range 16.6-33.1), 8/9 with widespread organ damage; median creatinine at the start of the diet: 3.2 mg/dl (1.2-7.2); 4 patients followed the diet to transplantation, 2 are presently on the diet, 2 dropped out and started dialysis after a few months, 1 started dialysis (rescue treatment). The nutritional status remained stable, glycemia control improved in 4 patients in the short term and in 2 in the long term, no hyperkalemia, acidosis or other relevant side effect was recorded. Proteinuria decreased in 5 cases, in 3 from the nephrotic range. Albumin levels remained stable; the progression rate was a loss of 0.47 ml/min of creatinine clearance per month (ranging from an increase of 0.06 to a decrease of 2.4 ml/min) during the diet period (estimated by the Cockroft-Gault formula). CONCLUSIONS Low-protein supplemented vegetarian diets may be a useful tool to slow CKD progression whilst awaiting pancreas-kidney transplantation.

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.

Daily dialysis Kt/V and flexible schedules: is it possible to control efficiency, when and how?

Background Daily hemodialysis is a promising treatment schedule but uniform criteria for defining efficiency are lacking. Methods On our daily dialysis (DD) schedule, duration is flexible (2–3 hours, patients are free to add up to 30min/session), Qb 250–350 mL/min; dialyser 1.6–1.8 m2. Study was performed on 12 pts on DD for ≥2 months, with ≥4 Kt/V on subsequent days, tested in the same laboratory. Goal: To evaluate variability and identify a simple method for weekly calculation, Kt/V was assessed for 133 sessions. Results On flexible DD, variability of Kt/V-session is high (relative error 4.9%-22%). On flexible schedules, within the time range chosen (2–3 hours) variability of average hourly Kt/V is lower (standard deviation: min (0.014; max (0.052 hour, relative error 4.9%-10%) allowing calculation of weekly Kt/V (averaging 3 sessions: relative error <6%) suitable for clinical practice. Conclusions Flexible schedules, allowing patients to increase treatment time, are an interesting clinical option, but a challenge for Kt/V assessment.

A Simple Method for the Classification of Proteinuria

We read with interest the paper of Bergon et al. about the classification of renal proteinuria (1) and we agree with the authors that in the presence of proteinuria or diagnosed nephropathy it is indispensable to measure protein excretion rate in a 24-hour urine collection using a dye-binding assay with pyrogallol-red (2, 3). Otherwise, in our experience a correct evaluation of proteinuria typing is a correct and feasible method that leads to a better standardization of the results. Furthermore, the assessment in mid-stream morning second urine samples by a nephelometric analysis of urinary proteins, using urinary protein/creatinine ratios allows a reduction of pre-analytical errors linked to urine time collection and to possible protein digestion by proteases action in 24-hour-stored urine (4). Recent studies shed new light into the physiopathlogical mechanisms of urinary protein excretion: thus, in our opinion a correct method of classification of proteinuria must distinguish not only between glomerular and tubular proteinuria but, in a better way, between selective glomerular proteinuria (presence of albumin and transferrin) and not selective glomerular proteinuria (presence of proteins with MW >100 kDa), and also between incomplete tubular proteinuria (presence of proteins with MW <50 kDa) and complete tubular proteinuria (presence of proteins with MW <23 kDa) (5). Data obtained showed that complete tubular proteinuria was an index of stronger tubular pathological involvement often associated to higher levels of serum creatinine and to a worse outcome (6). In our laboratory we developed an immunofixation method using specific polyclonal antisera, for qualitative/semi-quantitative analysis of urinary proteins (retinol-binding protein: RBP; α1-microglobulin: α1m; albumin; transferrin; immunoglobulin G: IgG and α2-macroglobulin: α2m), allowing a better definition of selectivity of glomerular proteinuria and of complete or incomplete tubular proteinuria (CSI-Nefro Cinque, BIOCI, Turin, Italy) (7). The CSI (Cross Star Immunofixation) method is a gel-immunoprecipitation, characterized by a high analytical sensitivity. This is due to the characteristics of the gel itself, to the mono-specificity of the antisera and to the new type of cross-deposition of the samples and

CKD patients and erythropoietin: do we need evidence-based informed consent?

Background Consent to therapy is increasingly requested in the form of “informed consent”. Objective To validate an evidence-based informed consent form for erythropoietin (EPO) therapy and to evaluate patient opinions about the informed consent approach. Methods An evidence-based informed consent form was developed as part of the Evidence-Based-Medicine course at the Medical School of Turin, Italy. It was validated by anonymous questionnaires (0–10 analogical scales and open answers) administered to patients at different stages of CKD (19 pre-ESRD, 26 hemodialysis, 12 transplant patients) attending an outpatient unit of the University of Turin, to 8 nurses, and to 26 medical students. Results All individuals filled in the questionnaire. Interest in a detailed explanation of the therapy was high (median 9), as was comprehension (median 9), with no differences between patients with regard to disease stage (pre-ESRD vs. RRT) or educational level. Prior knowledge of the therapy was affected by the educational level (p=0.013 for the advantages and p=0.004 for the side effects) and the professional role (patients vs caregivers: p=0.009 for the advantages and p<0.001 for side affects); patient knowledge of the advantages (median 6) tended to increase as the disease progressed (p=0.015). The most common response by patients was that informed consent was necessary for all drugs (35.1%); 73.1% of the caregivers considered it necessary only for severe side effects. The preferred modality of consent was discussion with the caregiver during the clinical controls (42% of all cases). Conclusions Patient interest in and comprehension of an informed consent form with a detailed explanation of the therapy was high; the caregivers opinion was still the most valued teaching tool.