Advertisement

Journal of Nephrology

, Volume 32, Issue 5, pp 741–750 | Cite as

Incremental hemodialysis, a valuable option for the frail elderly patient

  • Carlo BasileEmail author
  • Francesco Gaetano Casino
  • Filippo Aucella
Review
  • 261 Downloads

Abstract

Management of older people on dialysis requires focus on the wider aspects of aging as well as dialysis. Recognition and assessment of frailty is vital in changing our approach in elderly patients. Current guidelines in dialysis have a limited evidence base across all age group, but particularly the elderly. We need to focus on new priorities of care when we design guidelines “for people not diseases”. Patient-centered goal-directed therapy, arising from shared decision-making between physician and patient, should allow adaption of the dialysis regime. Hemodialysis (HD) in the older age group can be complicated by intradialytic hypotension, prolonged time to recovery, and access-related problems. There is increasing evidence relating to the harm associated with the delivery of standard thrice-weekly HD. Incremental HD has a lower burden of treatment. There appears to be no adverse clinical effects during the first years of dialysis in presence of a significant residual kidney function. The advantages of incremental HD might be particularly important for elderly patients with short life expectancy. There is a need for more research into specific topics such as the assessment of the course of frailty with progression of chronic kidney disease and after dialysis initiation, the choice of dialysis modality impacting on the trajectory of frailty, the timing of dialysis initiation impacting on frailty or on other outcomes. In conclusion, understanding each individual’s goals of care in the context of his or her life experience is particularly important in the elderly, when overall life expectancy is relatively short, and life experience or quality of life may be the priority.

Keywords

Elderly patients End-stage renal disease Frailty Incremental hemodialysis Residual kidney function Urea kinetic modeling 

Notes

Funding

No funding agency granted the present study.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    World Health Organization, Geneva, Switzerland (2010) Definition of an older or elderly person. http://www.who.int/healthinfo/survey/ageingdefnolder/en/index.html Accessed 3 Apr 2019
  2. 2.
    Orimo H, Ito H, Suzuki T et al (2006) Reviewing the definition of “elderly”. Geriatrics Gerontol Int 6:149–158CrossRefGoogle Scholar
  3. 3.
    Centers for Disease Control and Prevention (2003) Public health and aging: trends in aging—United States and worldwide. JAMA 289:1371–1373CrossRefGoogle Scholar
  4. 4.
    Coresh J, Selvin E, Stevens LA et al (2007) Prevalence of chronic kidney disease in the United States. JAMA 298:2038–2047CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang QL, Rothenbacher D (2008) Prevalence of chronic kidney disease in population-based studies: systematic review. BMC Public Health 8:117CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Arora P, Vasa P, Brenner D et al (2013) Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey. CMAJ 185:E417–E423CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bash LD, Astor BC, Coresh J (2010) Risk of incident ESRD: a comprehensive look at cardiovascular risk factors and 17 years of follow-up in the atherosclerosis risk in communities (ARIC) study. Am J Kidney Dis 55:31–41CrossRefPubMedGoogle Scholar
  8. 8.
    Gansevoort RT, Matsushita K, van der Velde M et al (2011) Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int 80:93–104CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Grams ME, Chow EK, Segev DL et al (2013) Lifetime incidence of CKD stages 3–5 in the United States. Am J Kidney Dis 62:245–252CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Anderson S, Halter JB, Hazzard WR et al (2009) Prediction, progression, and outcomes of chronic kidney disease in older adults. J Am Soc Nephrol 20:1199–1209CrossRefPubMedGoogle Scholar
  11. 11.
    Italian Registry of Dialysis and Transplant (RIDT). http://ridt.sinitaly.org/2017/10/09/report-2015/ Accessed 3 Apr 2019
  12. 12.
    United States Renal Data System (2014) Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. Incidence, prevalence, patient characteristics, and treatment modalities. Am J Kidney Dis 63(Suppl 1):e215–e228Google Scholar
  13. 13.
    Berger JR, Hedayati S (2012) Renal replacement therapy in the elderly population. Clin J Am Soc Nephrol 7:1039–1046CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lattanzio F, Corsonello A, Abbatecola AM et al (2012) Relationship between renal function and physical performance in elderly hospitalized patients. Rejuvenation Res 15:545–552CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Corsonello A, Fusco S, Bustacchini S et al (2016) Special considerations for the treatment of chronic kidney disease in the elderly. Expert Rev Clin Pharmacol 9:727–737CrossRefPubMedGoogle Scholar
  16. 16.
    Walker SR, Gill K, Macdonald K et al (2013) Association of frailty and physical function in patients with non-dialysis CKD: a systematic review. BMC Nephrol 14:228CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Fraser SD, Roderick PJ, May CR et al (2015) The burden of comorbidity in people with chronic kidney disease stage 3: a cohort study. BMC Nephrol 16:193CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Formiga F, Ferrer A, Sanz H et al (2013) Patterns of comorbidity and multimorbidity in the oldest old: the Octabaix study. Eur J Intern Med 24:40–44CrossRefPubMedGoogle Scholar
  19. 19.
    Clegg A, Young J, Iliff S et al (2013) Frailty in elderly people. Lancet 381:752–762CrossRefGoogle Scholar
  20. 20.
    Kojima G (2017) Prevalence of frailty in end-stage renal disease: a systematic review and meta-analysis. Int Urol Nephrol 49:1989–1997CrossRefPubMedGoogle Scholar
  21. 21.
    Musso CG, Jauregui J, Macías-Núñez J (2015) Frailty phenotype and chronic kidney disease: a review of the literature. Int Urol Nephrol 47:1801–1807CrossRefPubMedGoogle Scholar
  22. 22.
    Johansen KL, Chertow GM, Jin C et al (2007) Significance of frailty among dialysis patients. J Am Soc Nephrol 18:2960–2967CrossRefPubMedGoogle Scholar
  23. 23.
    Bao Y, Dalrymple L, Chertow GM et al (2012) Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med 172:1071–1077CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Fried LP, Hadley EC, Walston JD et al (2005) From bedside to bench: research agenda for frailty. Sci Aging Knowl Environ 31:24Google Scholar
  25. 25.
    Swidler M (2013) Considerations in starting a patient with advanced frailty on dialysis: complex biology meets challenging ethics. Clin J Am Soc Nephrol 8:1421–1428CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Farrington K, Covic A, Aucella F et al (2016) ERBP guideline development group. Clinical Practice Guideline on management of older patients with chronic kidney disease stage 3b or higher (eGFR < 45 mL/min/173 m2). Nephrol Dial Transplant 31(Suppl 2):ii1–ii66CrossRefPubMedGoogle Scholar
  27. 27.
    O’Hare AM, Choi AI, Bertenthal D et al (2007) Age affects outcomes in chronic kidney disease. J Am Soc Nephrol 18:2758–2765CrossRefPubMedGoogle Scholar
  28. 28.
    Urquhart-Secord R, Craig JC, Hemmelgarn B et al (2016) Patient and caregiver priorities for outcomes in hemodialysis: an international nominal group technique study. Am J Kidney Dis 68:444–454CrossRefPubMedGoogle Scholar
  29. 29.
    Aucella F, Stoico L, Cicchella A et al (2012) Comprehensive geriatric assessment in the hemodialysis elderly population. J Nephrol 25(Suppl 19):S85–S89CrossRefPubMedGoogle Scholar
  30. 30.
    Bansal N, Katz R, De Boer IH et al (2015) Development and validation of a model to predict 5-year risk of death without ESRD among older adults with CKD. Clin J Am Soc Nephrol 10:363–371CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Renal Physicians Association (2010) Shared decision-making in the appropriate initiation of and withdrawal from dialysis, 2nd edn. Rockville. https://cdn.ymaws.com/www.renalmd.org/resource/resmgr/Store/Shared_Decision_Making_Recom.pdf Accessed 3 Apr 2019
  32. 32.
    Mandel EI, Bernacki RE, Block SD (2017) Serious illness conversations in ESRD. Clin J Am Soc Nephrol 12:854–863CrossRefPubMedGoogle Scholar
  33. 33.
    Visser A, Dijkstra GJ, Kuiper D et al (2009) Accepting or declining dialysis: considerations taken into account by elderly patients with end-stage renal disease. J Nephrol 22:794–799PubMedGoogle Scholar
  34. 34.
    Raghavan D, Holley JL (2016) Conservative care of the elderly CKD patient: a practical guide. Adv Chronic Kidney Dis 23:51–56CrossRefPubMedGoogle Scholar
  35. 35.
    Brown EA, Finkelstein FO, Iyasere OU et al (2017) Peritoneal or hemodialysis for the frail elderly patient, the choice of 2 evils? Kidney Int 91:294–303CrossRefPubMedGoogle Scholar
  36. 36.
    Lomonte C, Basile C, Mitra S et al (2018) Should a fistula first policy be revisited in elderly haemodialysis patients? Nephrol Dial Transplant.  https://doi.org/10.1093/ndt/gfy319 CrossRefGoogle Scholar
  37. 37.
    Johansen KL, Delgado C, Bao Y et al (2013) Frailty and dialysis initiation. Semin Dial 26:690–696CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kurella TM, Covinsky KE, Chertow GM et al (2009) Functional status of elderly adults before and after initiation of dialysis. N Engl J Med 361:1539–1547CrossRefGoogle Scholar
  39. 39.
    Jassal SV, Chiu E, Hladunewich M (2009) Loss of independence in patients starting dialysis at 80 years of age or older. N Engl J Med 361:1612–1613CrossRefPubMedGoogle Scholar
  40. 40.
    Cooper BA, Branley P, Bulfone L, for the IDEAL Study et al (2010) A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med 363:609–619CrossRefPubMedGoogle Scholar
  41. 41.
    Basile C, Lomonte C (2012) Kt/V urea does not tell it. Nephrol Dial Transplant 27:1284–1287CrossRefPubMedGoogle Scholar
  42. 42.
    Corbett RW, Brown EA (2018) Conventional dialysis in the elderly. how lenient should our guidelines be? Semin Dial 31:607–611CrossRefPubMedGoogle Scholar
  43. 43.
    Wong S, Kreuter W, O’Hare AM (2014) Healthcare intensity at initiation of chronic dialysis among older adults. J Am Soc Nephrol 25:143–149CrossRefPubMedGoogle Scholar
  44. 44.
    Chazot C, Charra B, Van Vo C et al (1999) The Janus-faced aspect of “dry weight”. Nephrol Dial Transplant 14:121–124CrossRefPubMedGoogle Scholar
  45. 45.
    McIntyre CW, Burton JO, Selby NM et al (2008) Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. Clin J Am Soc Nephrol 3:19–26CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Costa AS, Tiffin-Richards FE, Holschbach B et al (2014) Clinical predictors of individual cognitive fluctuations in patients undergoing hemodialysis. Am J Kidney Dis 64:434–442CrossRefPubMedGoogle Scholar
  47. 47.
    Rayner HC, Zepel L, Fuller DS et al (2014) Recovery time, quality of life, and mortality in hemodialysis patients: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 64:86–94CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Davenport A, Guirguis A, Almond M et al (2019) Comparison of characteristics of centers practicing incremental vs. conventional approaches to hemodialysis delivery—postdialysis recovery time and patient survival. Hemodial Int.  https://doi.org/10.1111/hdi.12743 CrossRefPubMedGoogle Scholar
  49. 49.
    Gotch FA, Sargent JA (1985) A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 28:526–534CrossRefPubMedGoogle Scholar
  50. 50.
    Eknoyan G, Beck GJ, Cheung AK et al (2002) Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 347:2010–2019CrossRefPubMedGoogle Scholar
  51. 51.
    Lowrie EG (2008) Prescribing and monitoring hemodialysis dose. Kidney Int 74:262–264CrossRefPubMedGoogle Scholar
  52. 52.
    Tattersall J, Farrington K, Gentile G et al (2018) Is Kt/V useful in elderly dialysis patients? Pro- and Con arguments. Nephrol Dial Transplant 33:742–750CrossRefPubMedGoogle Scholar
  53. 53.
    Toth-Manikowski SM, Shafi T (2016) Hemodialysis prescription for incident patients: twice seems nice, but is it incremental? Am J Kidney Dis 68:180–183CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Lowrie EG, Laird NM, Parker TF et al (1981) Effect of the hemodialysis prescription of patient morbidity: report from the National Cooperative Dialysis Study. N Engl J Med 305:1176–1181CrossRefPubMedGoogle Scholar
  55. 55.
    NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy (2001) Update 2000. Am J Kidney Dis 37(Suppl 1):S7–S64Google Scholar
  56. 56.
    Daugirdas JT, Green T, Rocco MV et al (2013) Effect of frequent hemodialysis on residual kidney function. Kidney Int 83:949–958CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Golper TA, Mehrotra R (2015) The intact nephron hypothesis in reverse: an argument to support incremental dialysis. Nephrol Dial Transplant 30:1602–1604CrossRefPubMedGoogle Scholar
  58. 58.
    Mathew AT, Fishbane S, Obi Y et al (2016) Preservation of residual kidney function in hemodialysis patients: reviving an old concept. Kidney Int 90:262–271CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Rhee CM, Unruh M, Chen J et al (2013) Infrequent dialysis: a new paradigm for hemodialysis initiation. Semin Dial 26:720–727CrossRefPubMedGoogle Scholar
  60. 60.
    Kalantar-Zadeh K, Unruh M, Zager PG et al (2014) Twice-weekly and incremental hemodialysis treatment for initiation of kidney replacement therapy. Am J Kidney Dis 64:181–186CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Kalantar-Zadeh K, Casino FG (2014) Let us give twice-weekly hemodialysis a chance: revisiting the taboo. Nephrol Dial Transplant 29:1618–1620CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Fry AC, Singh DK, Chandna SM et al (2007) Relative importance of residual renal function and convection in determining beta-2-microglobulin levels in high-flux haemodialysis and on-line haemodiafiltration. Blood Purif 25:295–302CrossRefPubMedGoogle Scholar
  63. 63.
    Toth-Manikowski SM, Sirich TL, Meyer TW et al (2019) Contribution of “clinically negligible” residual kidney function to clearance of uremic solutes. Nephrol Dial Transplant.  https://doi.org/10.1093/ndt/gfz042 CrossRefPubMedGoogle Scholar
  64. 64.
    Masereeuw R, Mutsaers HA, Toyohara T et al (2014) The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol 34:191–208CrossRefPubMedGoogle Scholar
  65. 65.
    Leong SC, Sao JN, Taussig A et al (2018) Residual function effectively controls plasma concentrations of secreted solutes in patients on twice weekly hemodialysis. J Am Soc Nephrol 29:1992–1999CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Shafi T, Jaar BG, Plantinga LC et al (2010) Association of residual urine output with mortality, quality of life, and inflammation in incident hemodialysis patients: the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study. Am J Kidney Dis 56:348–358CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    van der Wal WM, Noordzij M, Dekker FW et al (2011) Full loss of residual renal function causes higher mortality in dialysis patients; findings from a marginal structural model. Nephrol Dial Transplant 26:2978–2983CrossRefPubMedGoogle Scholar
  68. 68.
    Vilar E, Wellsted D, Chandna SM et al (2009) Residual renal function improves outcome in incremental hemodialysis despite reduced dialysis dose. Nephrol Dial Transplant 24:2502–2510CrossRefPubMedGoogle Scholar
  69. 69.
    Marquez IO, Tambra S, Luo FJ et al (2011) Contribution of residual renal function to removal of protein-bound solutes in hemodialysis. Clin J Am Soc Nephrol 6:290–296CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Menon MK, Naimark DM, Bargman JM et al (2001) Long-term blood pressure control in a cohort of peritoneal dialysis patients and its association with residual renal function. Nephrol Dial Transplant 16:2207–2213CrossRefPubMedGoogle Scholar
  71. 71.
    Wang AY, Wang M, Woo J et al (2002) A novel association between residual renal function and left ventricular hyperthrophy in peritoneal dialysis patients. Kidney Int 62:639–647CrossRefPubMedGoogle Scholar
  72. 72.
    Golper TA (2016) Incremental hemodialysis: how I do it. Semin Dial 29:476–480CrossRefPubMedGoogle Scholar
  73. 73.
    NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy (2006) Update 2006. Am J Kidney Dis 48(Suppl 1):S2–S90Google Scholar
  74. 74.
    European Best Practice Guidelines Expert Group on Haemodialysis (2002) II.3 Haemodialysis dose and residual renal function (Kr). Nephrol Dial Transplant 17(Suppl 7):S24Google Scholar
  75. 75.
    Sandrini M, Vizzardi V, Valerio F et al (2016) Incremental peritoneal dialysis: a 10 year single-centre experience. J Nephrol 29:871–879CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Neri L, Viglino G, Marinangeli G, on behalf of Peritoneal Dialysis Study Group of Italian Society of Nephrology et al (2017) Incremental start to PD as experienced in Italy: results of censuses carried out from 2005 to 2014. J Nephrol 30:593–599CrossRefPubMedGoogle Scholar
  77. 77.
    Basile C, Casino FG, Kalantar-Zadeh K (2017) Is incremental hemodialysis ready to return on the scene? From empiricism to kinetic modelling. J Nephrol 30:521–529CrossRefPubMedGoogle Scholar
  78. 78.
    Garofalo C, Borrelli S, De Stefano T et al (2019) Incremental dialysis in ESRD: systematic review and meta-analysis. J Nephrol.  https://doi.org/10.1007/s40620-018-00577-9 CrossRefPubMedGoogle Scholar
  79. 79.
    Wong J, Vilar E, Davenport A et al (2015) Incremental haemodialysis. Nephrol Dial Transplant 30:1639–1648CrossRefPubMedGoogle Scholar
  80. 80.
    Lin YF, Huang JW, Wu MS et al (2009) Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis. Nephrology 14:59–64CrossRefPubMedGoogle Scholar
  81. 81.
    Obi Y, Streja E, Rhee CM et al (2016) Incremental hemodialysis, residual kidney function, and mortality risk in incident dialysis patients: a cohort study. Am J Kidney Dis 68:256–265CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Singh S, Choi P, Power A et al (2013) Ten-year patient survival and maintenance haemodialysis: association with treatment time and dialysis dose. J Nephrol 26:763–770CrossRefPubMedGoogle Scholar
  83. 83.
    van Olden RW, van Acker BA, Koomen GC et al (1995) Time course of inulin and creatinine clearance in the interval between two haemodialysis treatments. Nephrol Dial Transplant 10:2274–2280CrossRefPubMedGoogle Scholar
  84. 84.
    Tattersall J (2018) Residual renal function in incremental dialysis. Clin Kidney J 11:853–856CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Casino FG, Lopez T (1996) The equivalent renal urea clearance: a new parameter to assess dialysis dose. Nephrol Dial Transplant 11:1574–1581CrossRefPubMedGoogle Scholar
  86. 86.
    Tennekes HA, Sánchez-Bayo F (2013) The molecular basis of simple relationships between exposure concentration and toxic effects with time. Toxicology 309:39–51CrossRefPubMedGoogle Scholar
  87. 87.
    Casino FG, Basile C (2017) The variable target model: a paradigm shift in the incremental haemodialysis prescription. Nephrol Dial Transplant 32:182–190CrossRefPubMedGoogle Scholar
  88. 88.
    NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy (2015) Update 2015. Am J Kidney Dis 66:884–930CrossRefGoogle Scholar
  89. 89.
    Vilar E, Farrington K (2011) Emerging importance of residual renal function in end-stage renal failure. Semin Dial 24:487–494CrossRefPubMedGoogle Scholar
  90. 90.
    Casino FG, Basile C (2018) How to set the stage for a full-fledged clinical trial testing “incremental haemodialysis”. Nephrol Dial Transplant 33:1103–1109CrossRefPubMedGoogle Scholar
  91. 91.
    Casino FG, Basile C (2018) A user-friendly tool for incremental haemodialysis prescription. Nephrol Dial Transplant 33:1046–1053CrossRefPubMedGoogle Scholar
  92. 92.
    Basile C, Casino FG (2019) Incremental haemodialysis and residual kidney function. More and more observations but no trials. Nephrol Dial Transplant.  https://doi.org/10.1093/ndt/gfz035 CrossRefPubMedGoogle Scholar
  93. 93.
    Deira J, Suàrez MA, López F et al (2019) IHDIP: a controlled randomized trial to assess the security and effectiveness of the incremental hemodialysis in incident patienys. BMC Nephrol 20:8.  https://doi.org/10.1186/s12882-018-1189-6 CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Fernández-Lucas M, on behalf of Fundation para la investigation biomedica del Hospital Universitario Ramon y Cajal, Madrid, Spain. Incremental hemodialysis as a starting way of renal replacement therapy. ClinicalTrials.gov Identifier NCT03302546Google Scholar
  95. 95.
    Vilar E, on behalf of East and North Hertfordshire NHS Trust, Stevenage, UK. Does incremental initiation of haemodialysis preserve native kidney function? (Incremental HD). ClinicalTrials.gov Identifier NCT03418081Google Scholar
  96. 96.
    Courivaud C, on behalf of Centre Hospitalier Universitaire de Besancon, France. Quality of life of frail aged patients in incremental hemodialysis (Qualifragilys). ClinicalTrials.gov Identifier NCT03782519Google Scholar

Copyright information

© Italian Society of Nephrology 2019

Authors and Affiliations

  1. 1.Clinical Research Branch, Division of NephrologyMiulli General HospitalAcquaviva delle FontiItaly
  2. 2.Associazione Nefrologica Gabriella SebastioMartina FrancaItaly
  3. 3.Dialysis Centre SM2PotenzaItaly
  4. 4.Department of Nephrology and DialysisResearch Hospital “Casa Sollievo della Sofferenza”San Giovanni RotondoItaly

Personalised recommendations