Presente e futuro della terapia nutrizionale della CKD, razionale costi benefici

1. Presente e futuro della
terapia nutrizionale della
CKD, razionale costi
benefici
Dr. G. Quintaliani
Scuola di Specializzazione in Nefrologia -
Perugia

2. La nutrizione come causa di malattia
• WHO > Programmes and projects >
Nutrition
• Main content
• printable version
• Nutrition for Health and Development

3. La nutrizione come cura
• "diet therapy"[Subheading]

4. A low-nitrogen diet with protein of high biological value for severe chronic uremia. Giovannetti S, Maggiore Q: Lancet I:1100:1004,1964

7. Why then is dietary counseling used irregularly ?
We believe there are three major reasons:

8. Why then is dietary counseling used irregularly ?
We believe there are three major reasons:
(1) the initial MDRD report concluded that a low-
protein diet did not significantly slow
progression of CKI in nondiabetic patients
(2) designing these diets requires a skilled
dietitian, and this can be costly;
(3) changing the diet is difficult for some
patients;

9. Studi randomizzati e controllati
condotti in doppio cieco
Ricerca “in-vitro” e su modelli cellulari
Ricerca su modelli animali
Editoriali, rassegne, ed opinioni di “esperti”
Casi clinici
Serie di casi e Studi trasversali
Studi caso-controllo
Studi di coorte
RCT
DB
RCT
Studi randomizzati e
controllati
Meta-analisi
ClinicalTrials
Non tutto quello che trovate vi
serve….

13. REGIONI % VOLUME REGIONI
SICILIA 23,90%
UMBRIA + LAZIO 18,20%
CAMPANIA 16,10%
MOLISE + PUGLIA + BASILICATA 8,60%
TOSCANA 8,60%
CALABRIA 5,10%
LIGURIA 3,90%
VALLE D'AOSTA + PIEMONTE 3,50%
LOMBARDIA 2,90%
EMILIA ROMAGNA 2,60%
MARCHE + ABRUZZO 2,40%
SARDEGNA 2,00%
FRIULI VENEZIA GIULIA 1,40%
VENETO + TRENTINO ALTO ADIGE 0,70%
Il mercato aproteico

14. Studi randomizzati e controllati
condotti in doppio cieco
Ricerca “in-vitro” e su modelli cellulari
Ricerca su modelli animali
Editoriali, rassegne, ed opinioni di “esperti”
Casi clinici
Serie di casi e Studi trasversali
Studi caso-controllo
Studi di coorte
RCT
DB
RCT
Studi randomizzati e
controllati
Meta-analisi
ClinicalTrials
Non tutto quello che trovate vi
serve….

15. CONCLUSION: Dietary protein restriction effectively slows
the progression of both diabetic and nondiabetic renal diseases
Annals of Internal Medicine 1996Volume 124 Issue 7 Pages 627-
632

16. Fig. 1. Reduction in the odds of renal death in seven prospective
randomized studies of protein restriction in chronic renal insufficiency. A
square denotes the odds ratio (treatment/control) for each trial and the
diamond for the overall results. 95% CIs are represented by the horizontal
lines. Overall ‘common’ odds ratio=0.61 (95% CI: 0.46, 0.83), P=0.006.
Test for heterogeneity between studies: 2=4.84; degrees of freedom=6,
P=0.56.
Low protein diets delay end-stage renal disease in non-diabetic adults with
chronic renal failure
Denis Fouque,1,2, Ping Wang2,3, Maurice Laville1,2 and Jean-Pierre Boissel2
Nephrol Dial Transplant (2000) 15: 1986-1992

18. Terapia dietetica

20. 1.Antihypertensive agents for dialysis patients (Cochrane Protocol).
2.Antimicrobial agents for preventing peritonitis in peritoneal dialysis patientsFull Text
3.Bicarbonate versus lactate solutions for acute peritoneal dialysis (Cochrane Protocol).
4.Biocompatible dialysis fluids for peritoneal dialysis (Cochrane Protocol).
5.Biocompatible hemodialysis membranes for acute renal failureFull Text Available
6.Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patientsFull
7.Calcium dialysate concentration for peritoneal dialysis (Cochrane Protocol).
8.Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patientsFull Text Available (Cochrane Review).
9.Cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal diseaseFull Text Available (Cochrane Review).
10.Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home haemodialysis for end-stage renal disease in adultsFull Text Available (Cochrane
11.Continuous ambulatory peritoneal dialysis versus automated peritoneal dialysis for end-stage renal diseaseFull Text Available (Cochrane
12.Correction of chronic metabolic acidosis for chronic kidney disease patientsFull Text Available (Cochrane Review).
13.Cyclosporin versus tacrolimus for liver transplanted patientsFull Text Available (Cochrane
14.Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage renal diseaseFull Text Available (Cochrane
15.Effects of nonsteroidal anti-inflammatory drugs on postoperative renal function in adults with normal renal functionFull Text Available (Cochrane Review).
16.Emergency interventions for hyperkalaemiaFull Text Available (Cochrane Review).
17.Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patientsFull Text Available (Cochrane
18.Growth hormone for children with chronic kidney diseaseFull Text Available (Cochrane
19.Haemodiafiltration, haemofiltration and haemodialysis for end-stage kidney diseaseFull
20.Haemoglobin and haematocrit targets for the anaemia of chronic kidney diseaseFull Text
21.HMG CoA reductase inhibitors (statins) for dialysis patientsFull Text Available (Cochrane.
22.HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysisFull Text Available (Cochrane Review).
23.Immunosuppressive treatment for focal segmental glomerulosclerosis in adultsFull Text Available
24.Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndromeFull Text Available (Cochrane Review).
24.Intermittent versus continuous renal replacement therapy for acute renal failure in adultsFull Text Available (Cochrane Review).
25.Interventions for dialysis patients with hepatitis C virus (HCV) infection (Cochrane
26.Interventions for dialysis-associated restless legs syndrome (Cochrane Protocol).
27.Interventions for erythropoietin-resistant anaemia in dialysis patients (Cochrane Protocol).
28.Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura
29.Interventions for lowering plasma homocysteine levels in dialysis patients (Cochrane
30.Interventions for non-oliguric hyperkalaemia in preterm neonatesFull Text Available
31.Interventions for preventing bone disease in kidney transplant recipientsFull Text Available
32.Low protein diets for chronic kidney disease in non diabetic adultsFull Text Available
33.Medical adjuvant treatment to increase patency of arteriovenous fistulae and graftsFull Text
34.Physical measures for treating depression in dialysis patientsFull Text Available (Cochrane
35.Pre and peri-operative erythropoeitin for reducing allogeneic blood transfusions in colorectal cancer surgery.Full Text Available (Cochrane Review).
36.Protein restriction for children with chronic kidney diseaseFull Text Available (Cochrane
37.Psychosocial interventions for depression in dialysis patientsFull Text Available (Cochrane
38.Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patientsFull
39.Tidal peritoneal dialysis for acute renal failure (Cochrane .
40.Treatment for peritoneal dialysis-associated peritonitisFull Text Available (Cochrane
40.Vitamin D compounds for people with chronic kidney disease not requiring dialysisFull
41.Vitamin D compounds for people with chronic kidney disease requiring dialysis

22. A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy
and Safety of Cinacalcet HCl in Participants With CKD Not Receiving Dialysis
Volume 53, Issue 2, Pages 197-207 (February 2009)
• Conclusions These data show that cinacalcet treatment
in patients with CKD not receiving dialysis can decrease
plasma iPTH levels, but with frequent ((albeit generally
asymptomatic) serum calcium levels less than 8.4 mg/dL
and increases in serum phosphorus levels
• Limitations The study was not designed to assess the
effects of cinacalcet on vascular calcification, bone
histomorphometric parameters, or other clinical
outcomes. It is not known whether the observed
differences in changes in iPTH levels are clinically more
important than observed differences in changes in serum
calcium or phosphorus levels or dosages of vitamin D
sterols and phosphate binders.
American Journal of Kidney Diseases

23. • large prospective randomized study of sevelamer versus
calcium binders was undertaken in an effort to show
reduced mortality (the DCOR study), produced a
negative result,
• However, a subsequent post hoc analysis of subgroups
suggested a survival advantage for patients aged over 65
years, but the statistical and clinical validity of this finding
remains controversial.
• More recently, a secondary analysis found that treatment
with sevelamer versus calcium-based binders did not
affect overall mortality (primary outcome), cause-
specific mortality, morbidity, or first or cause-specific
hospitalization (secondary outcomes),

24. • The nephrologist should know that prescribing an aluminum-or calcium-free product for controlling
hyperphosphatemia in dialysis (sevelamer at the time of writing these lines) may suppose increasing
the costs by 209 euros per month, on average. Considering that each year 5,000 patients start on
dialysis, of which 50% have a phosphorus level > 5.5 mg/dL, the cost just for these incident
uncontrolled patients would be higher than € 6 million per year had they been treated with calcium-
free chelating agents.
• . Taking all this information together, and applying information we have available, the invoicing of
the only aluminum- and calciumfree phosphorus-chelating product available in our country is about €
20 million per year. And this expenditure seems not to be related with a decreased
hospitalization rate, cardiovascular events, or morbimortality.

27. Che cosa significa Farmaco Efficace
Efficacia terapeutica
Va intesa non solo come capacità di
correggere parametri biochimici o funzionali
alterati (efficacia clinica), ma soprattutto di
migliorare la qualità della vita o allungare la sua
durata (efficacia epidemiologica).
In altri termini l’efficacia va misurata sul
paziente, non (o non solo) sulla malattia

28. Rosuvastatina in dialisi studio poe vs doe
• Results After 3 months, the mean reduction in low-density lipoprotein (LDL)
cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline
level of 100 mg per deciliter.
• Rosuvastatin had no effect on individual components of the primary end point.
There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events
per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51).
• Conclusions In patients undergoing hemodialysis, the initiation of treatment with
rosuvastatin lowered the LDL cholesterol level but had no significant effect on the
composite primary end point of death from cardiovascular causes, nonfatal
myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number,
NCT00240331 [ClinicalTrials.gov] .)

29. Incidenza
153 / pmp
8721
Prevalenza
734 / pmp
41.000
SIN-RIDT
2009 Report Referring to the
Calendar Year 2007

30. Costi della CKD

31. Costi della dialisi
Costo annuale per la dialisi extracorporea di circa US $
51,252 per la dialisi al centro; $ 42,057 CAL/ CAD e., self
dialisi $ 29,961 e peritoneale. $ 26,959.
American Journal of Kidney Diseases, Vol 40, No 3 (September), 2002: pp 611-622

32. Il CENSIS suggerisce in Italia un costo della Emodialisi
in acetato o in bicarbonato (ospedaliera) di
63.885.457 Milioni di lire equivalenti a € 33.146,61
• In particolare l'indagine del Censis sui costi e
l'efficacia dei principali trattamenti dialitici rivela che
il costo totale, come somma di costo economico e
costo sociale, facente capo ai circa 39 mila pazienti
presenti in Italia risulta pari a quasi 2 mila e settecento
miliardi di lire, di cui circa 700 miliardi rappresentano
il costo sociale (pari a oltre un quarto del costo totale)
in gran parte ad esclusivo carico delle famiglie.
http://www.censis.it/277/372/4974/5112/5148/5149/content.ASP
Anno 2004

33. Costi dialisi CENSIS 2009
metodica costi indiretti costi diretti sociali tot settimana tot anno
HD 51,39 166,42 98,73 949,62 € 49.380,24
HDf 51,73 217,14 98,73 1102,8 € 57.345,60
APD 15,87 69,86 98,73 553,38 € 28.775,76
CAPD 14,81 55,3 98,73 506,52 € 26.339,04
http://www.censis.it/277/372/6697/6739/cover.asp

34. Dieta Ipoproteica e Sicurezza in Anziani CKD
Analisi primaria
DODE-study
RCT x sopravvivenza
GFR = 5 - 7 ml/min
Dieta 0,3 g/kg vs Dialisi
Pts>70 anni
Brunori G., Am J Kidney Disease 2007
Analisi ITT aggiustata :
HR per non inferiorità, p < 0.01
Reg Log, OR dieta = 2.21 (1.02-4.83); p = 0.04
Tempo mediano in dieta senza dialisi :
ឳ 1 anno

35. Blood pressure and time to ESRD
0
10
20
30
40
50
60
Time ( years )
BaselineGFR(ml/min)
0 2 4 6 8 10 12 14 16
MDRD Study A
Locatelli F and Del Vecchio L Nephrol Dial Transplant 1999;14:1360-4
Target blood pressure
- 3.5 ml / min / year
MAP 92 mmHg
MAP 107 mmHg
- 4.1 ml / min / year
' Time 1.24 years

36. Diet and time to ESRD
0
10
20
30
40
50
60
Time ( years )
BaselineGFR38.6ml/min)
0 2 4 6 8 10 12 14 16
MDRD Study A
Locatelli F and Del Vecchio L Nephrol Dial Transplant 1999;14:1360-4
- 3.6 ml / min / year
Low protein diet 9,3 years
Usual diet 8,3 years
- 4.03 ml / min / year
' Time 1. 0 years

37. Caratteristiche dell’MDRD Study I
• È stato ipotizzato che un paziente nefropatico inizi la
dieta ipoproteica con una GFR pari a 25 ml/min/1,73
m2.* e inizi la dialisi quando raggiunge una GFR di 5
ml/min/1,73 m2.°
• Applicando il declino medio della GFR ottenuto dal
MDRD Study I un soggetto trattato con una dieta a basso
contenuto di proteine (low protein diet) entra in dialisi
dopo circa 7 anni; un soggetto che segue una “usual
protein diet” dopo circa 5 anni.
* Livelli di GFR in cui secondo la comune pratica medica sarebbe opportuno iniziare una dieta ipoproteica
Ꮦ Livelli di GFR in cui secondo la comune pratica medica sarebbe opportuno iniziare il trattamento di
dialisi
Centro di Farmacoeconomia
Università degli Studi di Milano

38. Dieta per insufficienza renale cronica grave
(con utilizzo di prodotti aproteici)
con un apporto calorico di 2000 Kcal/4 - proteine 40 gr/die
* Prezzo €uro/ Kg
Ꮦ Tariffa SSN
Centro di Farmacoeconomia
Università degli Studi di Milano
123,9620,66 (€)*
Visita
specialistica
2023,89Costo totale
1899,93DIETA (prodotti)
Costo
annuale (€)*
Costi Alimentazione Ipoproteica/Y

39. COSTI
7 anni di dieta ipoproteica*
€ 15.000
* Valori attualizzati al 3%
BENEFICI
2 anni di
dialisi*
€ 98.000
EFFETTI
Dilazione di 2 anni
ingresso in dialisi
L’impiego di una dieta ipoproteica per 7 anni nel trattamento
dell’insufficienza renale cronica dilaziona l’ingresso in dialisi di
2 anni con un BENEFICIO NETTO di
98.000 – 15.000 = 82.000 € per paziente
Centro di Farmacoeconomia
Università degli Studi di Milano
Risultati

41. Diabete hb glicosilata
• Conclusions
• As compared with standard therapy, the use of
intensive therapy to target normal glycated
hemoglobin levels for 3.5 years increased mortality
and did not significantly reduce major cardiovascular
events. These findings identify a previously
unrecognized harm of intensive glucose lowering in
high-risk patients with type 2 diabetes.
(ClinicalTrials.gov number, NCT00000620.)

44. Results: Prevalence of medication noncompliance was
36.9% (95% confidence interval [95% CI], 28.6%-45.8%).

45. • Patient education programs have been shown to be an effective
adjunct to other methods of phosphate control.
• Sadly, randomized prospective outcome studies of the benefits of
reducing serum phosphate have yet to be undertaken, and the
achievement of targets set by opinion-based guidelines seem
to have become accepted 'outcomes' in themselves. It is to be
hoped that the eagerly awaited KDIGO CKD-MD guidelines will
acknowledge the lack of good quality data, and stimulate high
quality RCT-based research, rather than a plethora of
publications that seek only to measure the achievement of
biochemical targets. If so, perhaps we can really begin to
understand first the role of serum phosphate, and second, that of
oral phosphate binders, in the management of patients with CKD.

47. La dietista e i cambiamenti delle
abitudini alimentari

48. La dieta nella IRC
Gli alimenti ipoproteici e il loro uso

49. Dietista on line

50. • Conclusions: This study documented the frequency of dietitians performing job functions
related to renal dietetics. The results of this study document the variability in the role of renal
dietitian, and suggest differing levels of practice within renal dietetics.
• 2009 by the National Kidney Foundation,
• In daily practice, dietetics practitioners can
consistently demonstrate competency and value
as providers of safe, effective, and optimal
nephrology care. These standards also serve as
a professional resource for self-evaluation and
professional development for RDs specializing
in nephrology care. As a quality initiative of
the ADA RPG and the NKF CRN, the
standards themselves are an application of
continuous quality improvement concepts.
• 2009 by the National Kidney Foundation,

51. multidisciplinarità
• Infermieri
IRC
• Dietisti
• Nefrologi

54. integrated course involving
individual lectures on renal health, delivered by the
case-management nurse, according to the guidelines in a
standardized instruction booklet.
The lectures focused on nutrition, lifestyle, nephrotoxin
avoidance, dietary principles and pharmacological
regimens.
Further, the case-management nurse contacted the
patients to ensure timely follow-up.
All patients received dietary counselling from a dietitian.
Additionally, the case-management nurse often
contacted the participants via telephone to encourage
them to inform their nephrologists of their symptoms and
to reinforce the importance of medical visits.

55. Why then is dietary counseling used irregularly ?
We believe there are four major reasons:
(1) the initial MDRD report concluded that a low-
protein diet did not significantly slow
progression of CKI in nondiabetic patients
(2) designing these diets requires a skilled
dietitian, and this can be costly;
(3) changing the diet is difficult for some
patients;
We believe none of these are
sufficiently persuasive to avoid using
this time-tested therapy to prevent
complications of CKI