|Year : 2021 | Volume
| Issue : 1 | Page : 1-4
Ethics, justice, and statement of principles: Paving the way to newer living
Editor, Journal of Renal Nutrition and Metabolism, Department of Nephrology, SGPGIMS, Lucknow, Uttar Pradesh, India
|Date of Submission||12-May-2021|
|Date of Decision||20-May-2021|
|Date of Acceptance||30-May-2021|
|Date of Web Publication||21-Oct-2021|
Dr. Anita Saxena
Editor, Journal of Renal Nutrition and Metabolism, Department of Nephrology, SGPGIMS, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Saxena A. Ethics, justice, and statement of principles: Paving the way to newer living. J Renal Nutr Metab 2021;7:1-4
|How to cite this URL:|
Saxena A. Ethics, justice, and statement of principles: Paving the way to newer living. J Renal Nutr Metab [serial online] 2021 [cited 2023 Mar 30];7:1-4. Available from: http://www.jrnm.in/text.asp?2021/7/1/1/328957
“Life is short, and the Art long; the occasion fleeting; experience fallacious, and judgement difficult.” The physician must not only be prepared to do what is right himself but also to make the patient, the attendants, and the externals co-operate.,,
Hippocrates, the father of modern medicine, put forth the traditional oath of ideals and moral principles for the practicing medicine. The oath instructs physicians to treat the ill to the best of one's ability, to preserve a patient's privacy, and to carry forward the secrets of medicine to the next generation. It is the Hippocratic “oath,” which forms the basis of public ethical protection, that in the swearing of an oath the profession is restrained and safe, be that medicine and/or surgery. The world of medicine has evolved from “let food be thy medicine” to the revolutionary discovery of antibiotics, a milestone in modern medicine, providing healing and protection to life despite ghastly infections and preventing organ damage, to replacement of organs, awarding longevity despite burnt up organs, especially when vascular access options are lost.
Organ transplantation is a blessing to those who have lost hope of life because of end-organ damage. The earliest descriptions of organ transplantation are found in ancient Greek, Roman, Chinese, and Indian mythology involving bone, skin, teeth, extremity, and other organ transplantation.,,
Sadly, the demand of organs outnumbers the availability in general, but it is also exacerbated by the rising prevalence conditions which counter donation such as diabetes mellitus and obesity, thus reducing the donor pool. Therefore, in order to prevent any unethical and exploitative practices due to imbalance between the supply and demand, that would potentially result in misuse of poor and powerless people, especially the weaker sex, the Transplantation Society, and the International Society of Nephrology, convened a historical meeting at Istanbul in the year 2008 and carved uniform global practice of ethics in the field of organ transplantation such as Declaration of Istanbul (DOI), Declaration of Istanbul Custodian Group, and WHO Guiding Principles.
While transplantation not only bestows longevity, it also brings freedom from dialysis dependency. A successful kidney transplant restores near-normal renal function and corrects longstanding nutritional imbalances, and other comorbidities such as hyperparathyroidism, while others experience decline in renal function with the passage of time. It is likely that some patients may not attain optimal renal function due various factors ascribed to either donor characteristics and or surgical errors. Kidneys from different living donors may have very different outcomes. For deceased donors, factors such as age, gender, HLA mismatch, and ischemia time have been implicated, while in case of living-related transplants, donor characteristics such as pretransplantation workup (renal function), age of the donor, warm and cold ischemia time, extent of HLA matching, presence of comorbidity (hypertension) and, surgical expertise have a bearing on the outcome. The time on dialysis is the strongest modifiable risk factor for the outcome of renal allografts.
While transplantation restores life of a recipient, despite assurances of normal living for the donors, there have been concerns about the future health of the donor. Living renal donation can have long-term risks that may not be apparent in the short term A series from Norway encompassing 1800 donor nephrectomies reports a mortality of 0% with a rate of major perioperative complications of 2.1%. The numbers here reported underestimate the actual number of living donors with renal failure. Chronic kidney disease (CKD) is defined as estimated glomerular filtration rate (eGFR) lower than 60 ml/minute/1.73 m2 (using the MDRD formula) or by the presence of markers of kidney damage (such as albuminuria or abnormal imaging studies) for 3 months or more (NKF KDOQI™ guidelines 2002). Despite absence of markers of kidney damage which defines CKD, post nephrectomy, the eGFR of a large number of donors is below 60 ml/min/1.73 m.
Voluntary kidney donor is an otherwise healthy individual. Living uninephrectomy inevitably leads to reduced renal function, and is associated with an increase in proteinuria, rise in blood pressure,with increased risk of cardiovascular and all-cause mortality in VKD compared to the general population. Kidney donation inevitably leads to reduced renal function and is associated with an increase in proteinuria, as well as a rise in blood pressure (BP) greater than that attributable to normal aging. The initial loss of renal function is addressed in part by a vigorous compensatory response of the remaining kidney, including a 30% to 40% increase in GFR. Thus, mean GFR has been reported to be in the order of 70% to 75% of the value before nephrectomy. Favourable changes in kidney function follow living donor nephrectomy, document on an average increase in eGFR by 0.35 ml/min per 1.73 m2 per year (95% confidence interval [CI], 0.21 to 0.48), and decreased by −0.85 ml/min/1.73 m2 per year (95% CI, −0.94 to −0.75) in nondonors (P < 0.001). The incidence of clinical proteinuria after kidney donation quantified in 42 studies (follow-up of 4793 living donors over 2–25 years) reported incidence of proteinuria over 20%, whereas others reported >5% although there was significant heterogeneity between the studies (P = 0.0001). Proteinuria appeared to be increased after donation in three studies.,,Early reduction in glomerular filtration rate (GFR) is 30%–35%, in other studies 25%–40%, rather than a reduction by 50%, due to the compensatory hyperfiltration of the remaining kidney and 4 and 14% at 2 years after donation.
A systematic review of 8 studies has reported that 12% of donors developed a GFR between 30 and 59 ml/min per 1.73 m2, and 0.2% had a GFR <30 ml/min per 1.73 m2 over a mean follow-up that ranged between 3 and 20 years. The annual rate of eGFR decline is more rapid in older adults and males.
Hence, assessment of renal function in living kidney transplant donors before and after nephrectomy is important.
A series from Norway on 1800 donor nephrectomies reports a rate of major perioperative complications of 2.1%.
More recently, the increased use of “expanded criteria donor” and the changing profile of the potential donor pool has led to the increased use of organs from donors with a high comorbidity burden (for example, donors with diabetes mellitus).
The advent of the 5th century brought about changes in line with Hippocrates beliefs of medicine practice in Greece. The era saw the beginning of new developments in treatment never seen before. First and the foremost was the introduction of dietary regimen in therapy, which started to replace drug therapy and pharmacology. Greek medicine began to focus on aspects of diet and daily routine which would encourage good health and prevent illness. This was a new way of thinking about medicine, completely unattested in classical Babylonian medicine. This interest in diet and its effect on the body further led to more experimental measures to control body reactions to disease, and Greek physicians began to rely upon emetics and purgatives as basic treatments. All these were directed toward one goal, i.e. achieving proper balance within the body.
The medicine today continues to recognize the role of diet and specific foods as an adjuvant therapy in treating diseases. Diet and medicine are two inseparable components of holistic treatment. The most striking examples of this relationship are the cardiovascular and renal diseases, which without appropriate modifications in diet cannot achieve the treatment outcomes. In chronic kidney disease, dietary modifications are imposed although the journey of a patient right from predialysis to dialysis to post-transplantation period. Although VKD is a healthy individual (if not a marginal one), yet after nephrectomy, the donor due to decreased eGFR is counted/considered in the CKD category. Hence, KDIGO (2017) has proposed clinical practice guideline for evaluation and care of living kidney donors to assist medical professionals in not evaluating the living kidney donor candidates bit for providing care before, during, and after donation.
The guidelines propose a personalized postdonation care plan which includes postdonation blood pressure, BMI, and serum creatinine measurement with GFR estimation. and measurement of albuminuria at least once annually. Reinforcement of healthy lifestyle modifications is recommended such as regular aerobic exercise to maintain healthy weight) healthy diet and abstinence from potentially nephrotoxic agents such as tobacco, nonsteroidal anti-inflammatory drugs, and nephrotoxic medications and prevention of diseases that may cause CKD (e.g., hypertension, diabetes mellitus, CVD), and timely management of such diseases if they develop after donation. Data have shown that donors may have increased incidence of hypertension. Early detection and treatment of medical conditions that may subsequently affect GFR may protect the donor from further loss of GFR or other deterioration in health. Such conditions should be managed according to clinical practice guidelines either by the donor's primary care provider, or at the transplant center if appropriate care is available.
Since many donors develop low GFR, which meets the criteria for diagnosis of CKD, their risk of developing kidney failure someday is slightly higher as a result of donation and may eventually result in requirement of renal replacement therapy (dialysis or transplantation). Hence, post-donation monitoring for kidney disease and CKD risk factors is warranted. Living kidney donors should be monitored for CKD and managed according to the 2012 KDIGO CKD Guideline. Donors should also receive age-appropriate healthcare maintenance, and management of clinical conditions and health risk factors according to clinical practice guidelines for the local or regional population. Assessment of psychosocial metrics such as HRQoL has been recommended as part of postdonation follow-up to monitor general well-being, and to help transplant centers identify donors at risk for poor psychosocial outcomes.,,
Guidelines for metric thresholds indicating presence of an impairment that would prompt more attention by the clinician are not specifically defined in donors, but could be based on existing test standards (e.g. scores below 0.50 standard deviation of the normative mean on the “Short Form” (SF) class of measure, SF-36, 12, or 8). Transplant centers should educate donor candidates on the importance of follow-up, disclose donor responsibilities and potential costs of follow-up participation, and develop a personalized follow-up plan.,
Though voluntary donors are in the optimum medical condition, yet they should be included in a lifelong surveillance program.
A study on 71,468 living kidney donors with median (interquartile range) eGFR6 of 63 (54–74) mL/min/1.73 m2 has shown that the cumulative incidence of end-stage renal disease (ESRD) at 15 years post donation ranged from 11.7 donors per 10 000 donors with eGFR6 values >70 mL/min/1.73 m2 to 33.1 donors per 10 000 donors with eGFR6 values of 50 mL/min/1.73 m2 or less. Adjusting for age, race, sex, body mass index, and biological relationship, every 10 mL/min/1.73 m2 reduction in eGFR6, was associated with a 28% increased risk of ESRD (adjusted hazard ratio, 1.28 [95% CI, 1.06–1.54]; P = 0.009). Some studies conclude that preoperative obesity is a risk factor for GFR decrease and proteinuria after donation Modification in sugar blood levels was detected 6 months after nephrectomy.
Disturbances in FBS and postprandial sugar blood are associated with an increased risk of cardiovascular complications. These consequences can be more pronounced after nephrectomy. The presence of glucose intolerance increases the risk of developing diabetes by 5%–10% per year in the general population. Hyperlipidemia can also ensue in donors. Elevation of mean uric acid blood rates that could last up to three years after nephrectomy. Incidence of hyperuricemia can increase significantly starting from the 1st and 2nd year post donation, without reaching a pathological level, though the prevalence of hyperuricemia in the donors may be as low as 4%.
Hence, it is important that a VKD follows a diet which will not burden the kidney with excessive protein load and also ensure restrictions to prevent the development of hypertension. Donors should have their eGFR measured at 6 months post donation. Donors with low renal function may benefit from increased surveillance or early intervention to reduce end-stage renal disease risk.
This issue has picked up an article on ethics in organ transplantation to emphasize the fact that it is not only the donation of organs which is of paramount importance to give lease to a failing health, but due care and follow-up of kidney donors is equally important to prevent a noble life from progressing to a diseased state. Maintaining good nutritional status of a VKD is as important as building up nutritional status for better transplant outcomes for recipient. This issue also carries articles on COVID-19 viral clearance patterns in patients with kidney disease, community-acquired AKI in women, and their outcomes and highlights micronutrient deficiency in hemodialysis patients. For fresh passouts, there is a tutorial on disentangling dysbiosis in chronic kidney disease.
| References|| |
Ashby M. Goodbye Hippocrates? Bioeth Inq 2021;18:195-8.
Adams F. Aphorisms, epidemics 1, prognostics, and airs and waters. Presumed to be part of the book on ancient medicine or within the apocryphal de art. In: The Genuine Works of Hippocrates. Birmingham: The Classics of Medicine Library; 1985.
Adams CD. The Genuine Works of Hippocrates. New York: Dover Publications; 1868. Online at the Perseus Digital Library, Tufts University. Available from: https://catalog.perseus.org
. [Last accessed on 2021 Aug 30].
Fiddes PJ, Komesaroff PA. Hidden in plain sight: The moral imperatives of Hippocrates' first aphorism. J Bioeth Inq 2021;18:205-20.
Vanholder R, Domínguez-Gil B, Busic M, Cortez-Pinto H, Craig JC, Jager KJ, et al
. Organ donation and transplantation: A multi-stakeholder call to action. Nat Rev Nephrol 2021;17:1-15.
Shayan H. Organ transplantation: From myth to reality. J Investig Surg 2001;14:135-8.
Bergan A. Ancient myth, modern reality: A brief history of transplantation. J Biocommun 1997;24:2-9.
Bezinover D, Saner F. Organ transplantation in the modern era. BMC Anesthesiol 2019;19:32.
WHO guiding principles on human cell, tissue and organ transplantation As endorsed by the sixty-third World Health Assembly in May 2010, in Resolution WHA63.22 pages 1-9.
Lin J, Zheng X, Xie ZL, Sun W, Zhang L, Tian Y, et al
. Factors potentially affecting the function of kidney grafts. Chin Med J (Engl) 2013;126:1738-42.
Ellison MD, McBride MA, Taranto SE, Delmonico FL, Kauffman HM. Living kidney donors in need of kidney transplants: A report from the organ procurement and transplantation network. Transplantation 2002;74:1349-51.
Garg AX, Muirhead N, Knoll G, Yang RC, Prasad GV, Thiessen-Philbrook H, et al.
Proteinuria and reduced kidney function in living kidney donors: A systematic review, meta-analysis, and meta-regression. Kidney Int 2006;70:1801-10.
Boudville N, Prasad GV, Knoll G, Muirhead N, Thiessen-Philbrook H, Yang RC, et al.
Meta-analysis: Risk for hypertension in living kidney donors. Ann Intern Med 2006;145:185-96.
Matsushita K, van d V, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: A collaborative meta-analysis. Lancet. 2010;375:2073-81.
Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985;33:278-85.
Williams SL, Oler J, Jorkasky DK. Long-term renal function in kidney donors: A comparison of donors and their siblings. Ann Intern Med 1986;105:1-8.
Mathillas O, Attman PO, Aurell M, Brynger H. Glomerular filtration rate, hypertension and proteinuria after renal ablation: A long-term follow-up study in kidney donors. Scand J Urol Nephrol Suppl 1988;108:49-55.
Lam NN, Lloyd A, Lentine KL, Quinn RR, Ravani P, Hemmelgarn BR, et al.
Changes in kidney function follow living donor nephrectomy. Kidney Int 2020;98:176-86.
Gourishankar S, Courtney M, Jhangri GS, Cembrowski G, Pannu N. Serum cystatin C performs similarly to traditional markers of kidney function in the evaluation of donor kidney function prior to and following unilateral nephrectomy. Nephrol Dial Transplant 2008;23:3004-9.
Abdellaoui I, Azzabi A, Sahtout W, Sabri F, Hmida W, Achour A. Short- and long-term follow-up of living kidney donors. Saudi J Kidney Dis Transpl 2019;30:401-20.
] [Full text]
Hartmann A, Fauchald P, Westlie L, Brekke IB, Holdaas H. The risk of living kidney donation. Nephrol Dial Transplant 2003;18:871-3.
Cohen JB, Eddinger KC, Locke JE, Forde KA, Reese PP, Sawinski DL. Survival benefit of transplantation with a deceased diabetic donor kidney compared with remaining on the waitlist. Clin J Am Soc Nephrol 2017;12:974-82.
Geller MJ. Hippocrates, Galen and the Jews: Renal medicine in the Talmud. Am J Nephrol 2002;22:101-6.
Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, et al.
KDIGO clinical practice guideline on the evaluation and care of living kidney donors. Transplantation 2017;101 8 Suppl 1:S1-109.
Doshi MD, Goggins MO, Li L, Garg A×. Medical outcomes in African American live kidney donors: A matched cohort study. Am J Transplant 2013;13:111-8.
Andrassy KM. Comments on 'KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease'. Kidney Int 2013;84:622-3.
Litwin MS. Editorial comment: The psychosocial impact of donating a kidney. J Urol 1997;157:1600-1.
Manyalich M, Menjívar A, Yucetin L, Peri JM, Torres X, Dias L, et al.
Living donor psychosocial assesment/follow-up practices in the partners' countries of the ELIPSY project. Transplant Proc 2012;44:2246-9.
Weng FL, Reese PP, Waterman AD, Soto AG, Demissie K, Mulgaonkar S. Health care follow-up by live kidney donors more than three yr post-nephrectomy. Clin Transplant 2012;26:E300-6.
Weitz J, Koch M, Mehrabi A, Schemmer P, Zeier M, Beimler J, et al.
Living-donor kidney transplantation: Risks of the donor – Benefits of the recipient. Clin Transplant 2006;20 Suppl 17:13-6.
Massie AB, Holscher CM, Henderson ML, Fahmy LM, Thomas AG, Al Ammary F, et al.
Association of early postdonation renal function with subsequent risk of end-stage renal disease in living kidney donors. JAMA Surg 2020;155:e195472.
Goldfarb DA. Re: Kidney-failure risk projection for the living kidney-donor candidate. J Urol 2016;195:1823-4.
Kasiske BL, Anderson-Haag T, Israni AK, Kalil RS, Kimmel PL, Kraus ES, et al
. A prospective controlled study of living kidney donors: Three-year follow-up. Am J Kidney Dis 2015;66:114-24.
Rossi M, Campbell KL, Johnson DW, Stanton T, Haluska BA, Hawley CM, et al.
Uremic toxin development in living kidney donors: A longitudinal study. Transplantation 2014;97:548-54.
Hida M, Iida T, Shimbo T, Shiramizu T, Nakamura K, Saitoh H, et al.
Renal function after nephrectomy in renal donors. Tokai J Exp Clin Med 1982;7:511-6.