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Initiation And Incremental Dialysis


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Dr Wong KW …

Dr Wong KW

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    • 1. Initiation of dialysis and incremental dialysis Wong KW
    • 2. Initiation of dialysis
      • Most critical decision to make along the course of chronic renal insufficiency
      • Negative psychological impact on patients
      • Important socioeconomic implications
      • When to start - subject to much controversy
    • 3. Goals of dialysis
      • free of uremic symptoms
      • to control volume overload, acid-base and electrolyte disorders
      • and to provide a clearance of uremic toxins enough to allow an adequate dietary protein and caloric intake
        • When residual renal function fails to maintain all these vital functions, we have a solid argument for starting dialysis therapy
    • 4. Complications That May Prompt Initiation of Kidney Replacement Therapy
      • Intractable ECV overload
      • Hyperkalemia
      • Metabolic acidosis
      • Hyperphosphatemia
      • Hypercalcemia or hypocalcemia
      • Anemia
      • Neurological dysfunction (eg, neuropathy, encephalopathy)
      • Pleuritis or pericarditis
      • Otherwise unexplained decline in functioning or well-being
      • Gastrointestinal dysfunction (eg, nausea, vomiting, diarrhea, gastroduodenitis)
      • Weight loss or other evidence of malnutrition
      • Hypertension
    • 5. When to initiate?
        • The key question is whether we have to start dialysis prior to, or after the overt development of these uremic signs and symptoms
      • The beneficial effects that dialysis can offer to the pre-dialysis renal failure patient
      • the potential complications of dialysis, and the changes in the way of life that many patients have to endure, are factors which should temper this decision
    • 6. When to initiate?
      • How early is early?
      • Argument - since an adequate dose of peritoneal dialysis has been established to be a weekly Kt/V of >2.0(Ccl of 9 -1 4 ml/min), dialysis should be started to augment native clearance when it falls below this level
    • 7. What did the European Nephrologists think?
      • In an opinion survey about the initiation of dialysis carried out at the ERA-EDTA Congress (Nice, 2000) - majority of the participants answered that uremic signs and symptoms(38%), along with residual renal clearances(32%) were the most important criteria for judging when to initiate dialysis
      • less than 20% of participants thought that nutritional status was an important criterion to initiate dialysis
          • Initiation of dialysis - opinion from an International survey: Report on the Dialysis Opinion Symposium at the ERA-EDTA Congress, 18 September 2000, Nice
    • 8. KDOQI Guidelines (opinion)
      • When to Initiate Dialysis : K t/V urea Criterion (Opinion) patients should be advised to initiate some form of dialysis when the weekly renal Kt/V urea < 2.0. Unless:
        • 1. Stable or increased edema-free body weight.
        • 2. Nutritional indications
        • 3. Complete absence of clinical signs or symptoms attributable to uremia.
      • A weekly K r t/V urea of 2.0 approximates a kidney urea clearance of 7 mL/min and a kidney creatinine clearance that varies between 9 to 14 mL/min/1.73 m 2
    • 9. KDOQI Guidelines (opinion)
      • patients with chronic kidney failure (e.g, GFR < 15 to 20 ml/min) who are not undergoing maintenance dialysis, if protein-energy malnutrition (PEM) develops or persists despite vigorous attempts to optimize protein and energy intake and there is no apparent cause for malnutrition other than low nutrient intake, initiation of maintenance dialysis or a renal transplant is recommended (Opinion)
    • 10. KDOQI - second update of the Clinical Practice Guidelines (CPGs) and Clinical Practice Recommendations (CPRs)
      • Timing of therapy: When patients reach stage 5 CKD (estimated GFR < 15 mL/min/1.73 m2), nephrologists should evaluate the benefits, risks, and disadvantages of beginning kidney replacement therapy. Particular clinical considerations and certain characteristic complications of kidney failure may prompt initiation of therapy before stage 5 (B)
              • AJKD VOL 48, NO 1, SUPPL 1, JULY 2006
    • 11. Nephrol Dial Transplant (2002) 17 [Suppl 7 ]: 7 -1 5
      • Dialysis should be instituted whenever the GFR is -15 ml/min and there is one or more of the following:
        • symptoms or signs of uraemia,
        • inability to control hydration status or blood pressure,
        • or a progressive deterioration in nutritional status
      • In any case, dialysis should be started before the GFR has fallen to 6 ml/min/1.73 m, even if optimal pre-dialysis care has been provided and there are no symptoms
    • 12. Nephrol Dial Transplant (2002) 17 [Suppl 7 ]: 7 -1 5
      • High-risk patients e.g. diabetics may benefit from an earlier start. (Evidence level: C )
      • To ensure that dialysis is started before the GFR is 6 ml/min, clinics should aim to start at 8 -1 0 ml/min. (Evidence level: C )
    • 13. Nephrol Dial Transplant (2005) 20 [Suppl 9]
      • Dialysis should be instituted whenever evidence of uraemia is present, or blood pressure and hydration status cannot be controlled, or when a deterioration of the nutritional status is noticed. In any case, dialysis should be started before the GFR is <6 ml/min/1.73 m2 (creatinine clearance 8 ml/min/1.73 m2). (Evidence level C)
      • To ensure that dialysis is not started at a GFR of <6 ml/min/1.73 m2, initiation at the level between 8 and 10 ml/min should be considered. Diabetic patients may require an earlier start. (Evidence level C)
    • 14. CARI Guidelines (September 2004) No recommendations possible based on Level I or II evidence
      • Commence dialysis when GFR falls below approximately 10 mL/min/1.73 m2 if there is evidence of uraemia or its complications such as malnutrition. In occasional patients it may be necessary to initiate dialysis at a higher GFR. (Level III evidence)
      • If there is no evidence of uraemia or its complications including malnutrition, commence dialysis when GFR falls below approximately 6 mL/min/1.73 m2. (Level III evidence)
    • 15. CARI Guidelines (September 2004)
      • To encourage informed decision making, educate patients and staff about the strength of the evidence (at best, cohort studies) regarding the rationale for e arly dialysis initiation
      • Monitor GFR quarterly from value of 15- 2 0 mL/min/1.73 m2 and monthly from < 10 mL/min/1.73 m2 to avoid unintentional delay in initiation of dialysis
    • 16. CARI guidelines (September 2004)
      • Commence dialysis at first indication of malnutrition suspected to be due to uraemia and unresponsive to dietary intervention or correction of other reversible causes. (Level III evidence)
      • Use of a bsolute indications for dialysis initiation is a historical concept which is no longer valid, and their presence suggests delayed initiation. However, in some patients with co-morbid conditions, dialysis may be indicated for these reasons even when GFR is greater than 10 mL/min/1.73m2
    • 17. Canadian guidelines ( J Am Soc Nephrol 10: S287 -S 321, 1999)
      • GFR<120L/week/1.73m 2 (12ml/min), if symptoms/signs of uraemia, or evidence of malnutrition - recommend dialysis (level IV)
      • If asymptomatic, or malnutrition - monthly surveillance (opinion)
      • GFR<60L/week/1.73m 2 (6ml/min) - initiation of dialysis (opinion)
    • 18. Malaysian CPG
      • Dialysis should be initiated to promote wellness and not to rescue from illness
      • Dialysis should be started when:
        • Uraemic signs and symptoms
        • Weekly renal Kt/V <2.0 and/or
        • Indices of malnutrition developed in the absence of other causes
      • Dialysis should be initiated earlier in diabetics
    • 19. Postulate and practice
      • Several series of patients taken onto RRT - RRF (weekly Kt/V) at the start of dialysis - markedly lower than that of DOQI guidelines
      • Ranging between 0.68, 0.72 and 1.05 in patients reviewed in USA, Canada and UK
      • If DOQI guidelines are to be followed - dialysis needs to be started between 20 and 11 months earlier
      • Heavy additional burden
      • Must be justified by more convincing evidence to demonstrate unequivocal benefit from early initiation of dialysis
      • Prospective, controlled, randomized trials
    • 20. What is the evidence?
      • No RCTs are available yet
      • Several other cohort or case-control studies in dialysis patients have shown an association between serum albumin at initiation of dialysis and subsequent mortality
        • (Hakim & Lazarus 1995, Khan et al 1995, Spiegel et al 1993, Kopple et al 1995)
    • 21. Nutrition and renal failure
      • There is spontaneous decline in protein intake in patients with progressive renal failure, leading to sub-clinical malnutrition
      • Consequently, patients with CRF must be carefully followed for evidence of weight loss, global nutritional assessment, and objective evidence of dietary protein intake from urea kinetics
    • 22. Nutrition and residual renal function
      • Ikizler et al 1995 -
        • spontaneous dietary protein intake (DPI) fell with creatinine clearance (CCr).
        • DPI at CCr 10 mL/min was 0.54 g/kg/day, and ideal body weight fell by 0.38% for each 10 mL/min fall in CCr.
        • The fall in spontaneous DPI was evident when GFR fell below 25 -5 0 mL/min
    • 23. Nutrition and RRF
      • Patients with chronic renal failure on an unrestricted diet tend to decrease their protein intake as the renal failure progresses
      • A direct correlation was noted between the dietary protein intake and the creatinine clearance (Ccr):
        • 1.1 g/kg per day at a Ccr above 50 mL/min
        • 0.85 g/kg per day between 25 and 50 mL/min
        • 0.70 g/kg per day between 10 and 25 mL/min
        • 0.54 g/kg per day below 10 mL/min
      • These changes, which presumably reflect anorexia induced by renal failure, question the safety of restricting protein intake in patients with a creatinine clearance below 25 mL/min
    • 24. Nutrition
      • CANUSA study (McCusker et al 1996)
        • normalized protein catabolic rate (nPCR) at entry correlated with RRF at entry, and 2-year survival correlated with malnutrition as assessed by serum albumin, subjective global assessment score, % lean body mass or nPCR
      • Lower GFR was associated with lower protein intake and lower serum albumin level (Kopple et al, KI 57: 1688-1703, 2000)
      • Serum albumin level at the initiation of dialysis was a powerful predictor of death ( Owen WF et al. N Engl J Med 1993 Sep 30;329(14):1001-6)
    • 25. Malnutrition at initiation of dialysis
    • 26. Malnutrition at initiation of dialysis
    • 27. Malnutrition at initiation of dialysis
      • It is uncertain whether malnutrition is a surrogate marker for other factors that determine mortality
      • In dialysis patients, increased mortality is largely due to cardiovascular causes, whereas in malnourished patients with normal renal function, increased mortality is the result of infection
    • 28. Early initiation - believers
      • Early initiation of dialysis - on presumption that it improves nutrition, decreases hospitalization rates, reduces mortality (observational data) - first proposed by Bonomini et al
    • 29. Early initiation - believers
    • 30.  
    • 31. Bonomini et al, 1985
      • reported that an early start of dialysis was associated with reduced mortality and morbidity
      • Among a subset of patients who were subsequently transplanted, there was a survival advantage for those started dialysis early (n=50) vs later (n=96), as well as less vascular calcification, bacterial infection, dyslipidaemia and hospitalization
    • 32. Early initiation - believers
      • CANUSA Study (McCusker et al 1996) - significantly poorer survival for patients with lower levels of renal function when starting dialysis
      • The mean creatinine clearance at the start of dialysis for all patients was 38 L/wk (3.8 ml/min)
      • 12 and 24 m onth survival for those with creatinine clearance <38 L/wk at start of dialysis was 82.1% and 73.6%, respectively, compared with 94.7% and 90.8%, respectively, for those with creatinine clearance >38 L/wk
    • 33. Early initiation - believers
      • In the CANUSA study, there was a survival advantage for higher total (residual plus dialysis) Kt/V up to 2.0, and possibly up to 2.3
      • Based on these data in patients on peritoneal dialysis (PD), many authors have argued that it is logical to start dialysis at a level of residual renal function equivalent to the target total Kt/V
      • This study was not designed to examine time of initiation of dialysis
    • 34. Early initiation - believers
      • Tattersall et al. demonstrated reduced survival in patients with less residual renal function at start of dialysis, although these patients were also significantly older and had significantly more co-morbidity
      • prospective cohort study of 63 patients in 1991–92
      • Hospitalization length of stay was greater among those with residual Kt/V <1.05 at time of initiation of dialysis
      • ( Am J Nephrol 15: 283 -2 89, 1995)
    • 35. Early initiation - believers
      • Another study - Schulman G and Hakim RM
      • patients initiated on dialysis with a creatinine clearance > 10 ml/min had an 88% 10- year survival when compared to 55% in those initiated at a creatinine clearance of < 10 ml/min (mean 4 ml/min)
          • Improving outcomes in chronic hemodialysis patients: should dialysis be initiated earlier? Semin Dial 1996; 9(3):225-9
    • 36. Early initiation
      • However, early initiation of dialysis expose patients : complications of dialysis, unnecessary lifestyle restriction, potential increased cost, patient fatigue
      • No RCTs - Confounding influences in other studies include referral time bias, age, co-morbidity, patient compliance and starting time bias
      • Lead time bias
    • 37. Early initiation - skeptics - lead time bias
      • In the context of initiation of dialysis, lead-time bias refers to the effect whereby measuring survival from the start of dialysis increases apparent survival of those started with more residual renal function i.e., earlier in the course of the disease, than those who start dialysis with less residual renal function
    • 38. Early initiation - skeptics - lead time bias
      • In NECOSAD study (Korevaar et al.) estimated the effects of lead-time bias on dialysis survival by using prediction software based on the Finnish Cancer Registry
      • timely initiation - associated with a small survival benefit of 2.5 months
      • However, the extra time free of dialysis for “l ate starters ” was only 4.1 months
      • This study suggested that any perceived survival benefit from early start could be accounted for by lead-time
              • When to initiate dialysis: effect of proposed US guidelines on survival. Korevaar et al. Lancet 2001 Sep 29; 358(9287):1046-1050
    • 39. Early initiation - skeptics - QOL
      • In a prospective cohort study from Holland (Korevaar et al 2002), 38% of 237 incident dialysis patients commenced dialysis late, as defined by the K/DOQI guidelines. Compared with patients who have timely initiation, the HRQOL among late starters was worse during the first 6 months after initiation, but no different at 12 months.
      • (Evaluation of DOQI guidelines: Early start of dialysis treatment is not associated with better health-related quality of life. Am J Kidney Dis 2002; 39:108- 1 15)
    • 40. Early initiation does not prolong survival?
      • Traynor et al ( J Am Soc Nephrol 13: 2125 -2 132, 2002) - using electronic patient record to include patients to calculate the time point at eCCr of 20ml/min (used to time survival)
      • Divided into early and late start groups by median eCCr for all patients at initiation of dialysis - 8.3ml/min
      • No significant benefit in patient survival from earlier initiation of dialysis
      • Cox proportional hazards model demonstrated significant inverse relationship between eCCr at start of dialysis and survival, even after adjustment of gender, age, weight, presence of DM, mode of first dialysis, Hb, albumin
    • 41. Early initiation does not prolong survival?
      • In a post-hoc analysis of the MDRD study, comparing early (predicted MDRD GFR>7.5 ml/min; N = 1,444) with late (predicted GFR <7.5 ml/min); N = 1,476), higher MDRD GFR (but not measured creatinine clearance) at initiation was associated with an increased risk of death in multivariate Cox model (hazard ratio 1.27 for each 5 ml/min increase)
      • “ reflect an erroneous GFR estimation by MDRD formula”
      • Concluded that the data do not support early initiation of dialysis
              • Impact of timing of initiation of dialysis on mortality. Beddhu et at. JASN 14: 2305-2312, 2003
    • 42. Early initiation of dialysis increases risk of mortality?
      • Kazmi et al - undertook an evaluation of the impact of comorbidity on the association between GFR at initiation and death
      • Results: greater GFR at initiation associated with a greater risk for death in all populations
      • Patients in the general dialysis population who initiated dialysis therapy at a GFR >10 mL/min/1.73 m2 had a 42% increased risk for death compared with patients with a GFR < 5 mL/min/1.73 m2 at initiation of dialysis therapy after adjusting for all covariates
      • Additional research required
              • Am J Kidney Dis. 2005 Nov;46(5):887-96
    • 43. The problem of measuring residual renal function(RRF)
      • Selecting the best, or the least erroneous, indicator for measuring RRF
      • Serial measurement of creatinine, 1/creatinine, creat clearance per BSA
      • Calculation of GFR by (Ccr + Urea clearance per 1.73m 2 )/2
      • Over-estimation of GFR by Ccr measurement needs to be stressed
      • Use of Kt/V - indicator of RRF or adequacy of dialysis - also open to criticism due to error in evaluating the volume of distribution of urea in clinical practice
    • 44. The problem of measuring residual renal function(RRF)
      • CARI guidelines: GFR calculated as the mean of urea and creatinine clearance corrected for BSA
      • NDT guidelines:
        • A. GFR should only be estimated using a method, which has been validated in patients with advanced renal failure. The preferred method for calculating GFR in advanced renal failure is the mean of urea and creatinine clearance . The latter is best calculated from a 24-h urine collection and normalized to 1.73 m2. (Evidence level: C)
        • B. Other examples of validated GFR estimations are:
          • MDRD equation
          • Indicator decay methods (e.g. iohexol, iothalamate, EDTA, inulin)
          • Creatinine clearance after oral cimetidine
    • 45. Definite answer? IDEAL TRIAL
      • The IDEAL trial (Cooper et al 2004) is a multicentre RCT that aims to determine whether it is better to commence dialysis with a creatinine clearance of 10–14 or 5–7 mL/min/1.73 m2. Randomization of 800 patients should be completed by mid-2005, with a 3-year follow-up at the end of the recruitment period
    • 46. Incremental dialysis?
      • Say we have decided to initiate dialysis early, either HD or PD,
      • How to start?
    • 47. Incremental dialysis
      • Most guidelines recommend when to start (opinion based) but not HOW to start
      • DOQI - incremental or full PD, to keep weekly total Kt/V>2.0; twice- or thrice- weekly HD, with biocompatible membrane
      • Once decision made to start - ‘full dose’, ignoring the RRF component; or
      • “ i ncrementally” initiate dialysis adding PD or HD to the RRF component maintaining minimal total target Kt/Vurea clearance goals at all times
    • 48. Should We Treat Patients with Incremental Dialysis Prescriptions?
      • By definition, i ncremental dialysis is the process of prescribing dialysis with the aim of maintaining a minimal total (PD, or HD and residual renal) solute clearance goals at all times, increasing the dialysis component (dose) when necessary so that when added to that solute clearance from residual renal clearance the minimal total solute clearance goals are always maintained (Golper TA: Incremental dialysis. J Am Soc Nephrol 1998;9:S107- S 111)
    • 49. Incremental dialysis - Bonomini et al
      • Bonomini et al. - incremental approach in prescribing dialysis 1985
      • 82 patients started HD treatment twice/week over a 15-year period with a mean creatinine clearance of 11ml/ min vs 308 patients treated by a low-protein diet for 24 - 53 months then starting dialysis with a mean RRF creatinine clearance of 2 -5 ml/min
      • Those started dialysis incrementally tended to preserve RRF if dehydration on dialysis was avoided
      • a better 12-year crude mortality rate, less severe vascular calcification at the time of transplantation, spent less days/ year hospitalized, and the total cost of medical care was less than the late starters
    • 50. Incremental dialysis - Williams et al
      • Williams et al - initiated PD in 15 patients using one overnight polyglucose exchange
      • Keep weekly Kt/Vurea >2, total creatinine clearance >100L/1.73m2 at all times
      • 4 patients increased the number of daily exchanges, 1 transplanted, 1 recovered renal function
      • Baseline RRF 1.96+0.38(Kt/Vurea)
      • Concluded some patients can be maintained on one overnight exchange for many months, most uneventful course, occasionally a decrease in RRF, requiring an increase in dialysis dose
      • Initial clinical experience positive in terms of patient acceptance, minimal life style disruption and ease of therapy management
              • Williams PF, Timely initiation of dialysis. AJKD, 1999; 34:594-595
    • 51. Incremental dialysis - Devecchi et al
      • DeVecchi A, Scalamonga A: Preliminary experience with incremental peritoneal dialysis in 17 patients (abstract). Perit Dial Int 1999; 19(suppl 1):S23. 27
      • In a cohort of 17 Italian patients followed for a maximum of 21 months, the patients did well. There were 2 episodes of peritonitis and 6 exit site infections
      • dialysis was started when the creatinine clearance < 6 m L/min, but this equated to a measured Kt/V urea of 1.28 at start, and only when the patients went to three exchanges did the Kt/V value >2 - considered as late start by KDOQI, and a single or two exchanges did not provide for adequate clearance
    • 52. Incremental dialysis - Foggensteiner et al
      • Another nonrandomized prospective pilot study - 39 patients
      • Patients were started on a single exchange of dialysate overnight. Dialysis adequacy was monitored at least every 2 months and incremental increases in dialysis were used to maintain combined urinary and dialysis Kt/V >2.0
      • Median actuarial survival on a single exchange before requiring incremental dialysis was 297 days
      • At the end of the study period, all patients were still alive: 8 remained on 1 exchange, 18 were on more than 1 exchange, 8 switched to hemodialysis, and 5 had received renal transplant
      • 2 episodes of bacterial peritonitis, 3 pleural leaks, 1 patent processus vaginalis, and 1 inguinal hernia that required surgical intervention
              • Foggensteiner et al. , Peritoneal Dialysis International, Vol. 22, pp. 471 -4 76
    • 53. Incremental dialysis - Keshaviah et al
      • Keshaviah et al, using urea kinetic model, showed - a hypothetical average sized patient, treated with CAPD with high average peritoneal transport - (initial urea clearance of 7.5ml/min, urea generation rate of 8.5g/day) could maintain a Kt/V of 2.0 for 8 months with a single 2.5L nocturnal exchange, and up to 17 months with two 2.5L nocturnal exchanges
      • With haemodialysis - this goal can be achieved during 5 months with one weekly HD session, gradually increased from 1 to 8 hours, followed up to 36 months by a weekly regimen of two HD sessions gradually increased duration from 1.5 to 6h each
              • Keshaviah et al. Timely initiation of dialysis: a urea kinetic approach. Am J Kidney Dis 1999; 33:344-8.
    • 54. The Wake Forest Experience - Burkart et al
      • Pilot study to gain clinical experience with an i ncremental approach to the initiation of dialysis
      • Patients recruited to start dialysis once weekly Kt/Vurea <2.0, and if one or more DOQI criteria present
      • Incremental dialysis to keep Kt/Vurea >2.0 per week
      • 15 patients (13 PD, 2 HD)
      • At the end of observation period - all patients increased no. of daily exchanges
      • Improvement in blood pressure control, decrease in no. of antihypertensives
      • 3 died (one from line sepsis after AVR, one from pneumonia, and one from peritonitis while on full dose PD)
      • Miscellaneous complications - Tenckhoff migration, hernia repair, pleural leak, damaged Tenckhoff, elective transplant nephrectomy, one episode of peritonitis
      • They concluded incremental dialysis can be used to maintain total solute clearance goals, patients accepted the approach and readily changed prescription when instructed
              • Peritoneal Dialysis International, Vol. 20, pp. 418 -4 22
    • 55. Incremental dialysis
      • These clinical experiences can be interpreted as favorable toward i ncremental initiation of dialysis.
      • However, long-term outcomes are not yet known, and this may dissuade clinicians from using this approach
    • 56. Some Considerations for Incremental Dialysis
      • PD or HD?
        • Initiation of dialysis using PD would potentially - a beneficial effect on preservation of renal function
      • CAPD or APD? - preliminary observations that APD may be more disadvantageous than CAPD for the preservation of RRF
      • Cost?
        • Bonomini et al. described that total health system costs were reduced by the healthy start approach. More data to suggest that a healthy start is medically better and less costly are needed (Bonomini V, Baldrati I, Stefoni S: Comparative cost/benefit analysis in early and late dialysis. Nephron 1983;33:1 -4 )
    • 57. Potential Obstacles
      • Failure to follow patients in a timely manner for initiation of ‘healthy start’ dialysis
      • Patient and family must become knowledgeable of the modality options available, with understanding of the need to adjust dialysis doses for further deterioration of RRF
      • Close monitoring and proactive interventions to maintain total solute clearance - requiring fully committed members of the renal replacement team
      • To measure total solute clearance - familiar and that works - but no published outcome data for those initiated with incremental approach
    • 58. Risk of incremental dialysis?
      • Risk of infection
      • CAPD registry showed risk of peritonitis significantly less with fewer exchanges per day ( Final report of the CAPD Registry edited by Lindblad AS, Novak JW, and Nolph KD. Dordecht: Kluwer Academic, 1989:223-8)
      • Earlier “burnout”
      • Measures to preserve RRF - avoidance of nephrotoxic drugs, minimal use of contrast, good control of BP, ?use of more biocompatible membranes
    • 59. Incremental dialysis advantages and disadvantages
      • Advantages
        • Cost savings
        • Reduced glucose exposure and protein loss
        • Less membrane ‘fatigue’
        • Greater patient acceptance
      • Disadvantages
        • Frequent and close monitoring of RRF
        • Frequent prescription changes
        • Uncertainty about the effect on outcome
    • 60. Alternative to early start of dialysis?
      • Dietary protein restriction - ameliorates uremic symptoms and slows progression of renal failure
      • Modification of Diet in Renal Disease (MDRD) study(1994), demonstrated a small but not statistically significant benefit in the progression of renal disease from dietary protein restriction
      • Secondary analyses of the data showed clinical benefit only in patients with severe renal failure as- signed to the low-protein group
      • Issues - availability of dietitian, inducing malnutrition, compliance
    • 61. Can renal replacement be deferred by a supplemented very low-protein diet?
      • 76 patients with a residual GFR of <15 -1 0 ml/min -submitted to a diet of 35 kcal BW/day containing 0.3 g protein/kg/BW supplemented with 10 g of essential amino acids or 2.8 g/10 kg BW of keto-acids
      • During the 93 patient-years period of observation -
        • the annual mortality was 2.5%
        • hospitalization episodes 0 -2 per patient-year.
        • The median renal survival to dialysis was 363 days ranging from 1 week to 4 years.
      • No significant deterioration of biological nutritional indices was observed between the start of dietary treatment and initiation of dialysis
              • Walser M, Hill S J Am Soc Nephrol 1999; [10]: 110 -1 16
    • 62. Finally,
      • it can be reasonably stated that timely initiation of dialysis treatment cannot be based merely on numerical data, but should be decided according to the overall clinical tolerance of each individual patient to his or her advanced stage of uraemia, the most important parameters to be considered being; adequate control of blood pressure and quality of nutritional status. Initiating dialysis at the right time for a given patient with the most appropriate technique represents a sophisticated exercise of clinical medicine, which remains, and will remain a balanced mixture of Science and Art