Long-term Kidney Transplant Survival Across the Globe.

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

Choosing the larger kidney on CT volumetry: a study on the early post-donation kidney function of living donors.

BACKGROUND: Selecting the smaller kidney for donation has been advocated if there is a size difference of > 10% between the 2 kidneys but has never been prospectively evaluated. With increase in donor nephrectomies, it is important to evaluate this to minimize loss of renal function to donors. METHODS: 75 consecutive donor nephrectomy patients were included in our longitudinal study. The Split Renal Volume (SRV) of bilateral kidneys were measured using contrasted computer tomography scans and patients segregated into 2 groups depending on donated kidney having more (Group 1) or less than (Group 2) 52.5% of SRV. RESULTS: Patients in Group 1 (n = 19) and 2 (n = 56) were of similar age (43.8 vs. 48.3), BMI (22.4 vs. 25.2), sex (57.9 vs. 55.4% women), respectively. Although total kidney volumes were similar in both groups, Group 1 had significantly smaller right kidney volumes (120.4 ± 24.9 vs. 142.7 ± 28.4 mls, p = 0.003). EGFR pre-operatively (116.3 ± 20.8 vs. 106.3 ± 23.8 mL/min/1.73 m2) and at 6-months (65.7 ± 13.3 vs. 66.9 ± 15.5 mL/min/1.73 m2) were not different between groups. However, patients in Group 1 had significantly greater absolute (50.6 ± 14.9 vs. 39.5 ± 14.7 mL/min/1.73 m2) and relative decline (43.0 ± 8.6 vs. 36.3 ± 10.6%) in eGFR at 6 months (p = 0.06, 0.009). CONCLUSION: With a SRV difference of 5% between the 2 sides, removal of the larger kidney for living kidney donation resulted in greater early decline of renal function than kidney donors whose larger or equivalent kidney is preserved.

Healthy aging and chronic kidney disease

The world population is aging and the prevalence of noncommunicable diseases such as diabetes, hypertension, and chronic kidney disease (CKD) will increase significantly. With advances in medical treatment and public health, the human lifespan continues to outpace the health span in such a way that the last decade of life is generally spent in poor health. In 2015, the World Health Organization defined healthy aging as ‘the process of developing and maintaining the functional ability that enables wellbeing in older age.’ CKD is increasingly being recognized as a model of accelerated aging and is associated with physical performance decline, cognitive decline, falls and fractures, poor quality of life, loss of appetite, and inflammation. Frailty and dementia are the final pathways and key determinants of disability and mortality independent of underlying disease. CKD, dementia, and frailty share a triangular relationship with synergistic actions and have common risk factors wherein CKD accelerates frailty and dementia through mechanisms such as uremic toxicity, metabolic acidosis and derangements, anorexia and malnutrition, dialysis-related hemodynamic instability, and sleep disturbance. Frailty accelerates glomerular filtration decline as well as dialysis induction in CKD and more than doubles the mortality risk. Anorexia is one of the major causes of protein-energy malnutrition, which is also prevalent in the aging population and warrants screening. Healthcare systems across the world need to have a system in place for the prevention of CKD amongst high-risk older adults, focusing on screening for poor prognostic factors amongst patients with CKD such as frailty, poor appetite, and cognitive impairment and providing necessary person-centered interventions to reverse underlying factors that may contribute to poor outcomes.

A Multiethnic Asian Perspective of Presumed Consent for Organ Donation: A Population-Based Perception Study.

Background: Organ shortage is still a world-wide problem, resulting in long waiting lists for kidney, liver, and heart transplant candidates across many transplant centers globally. This has resulted in the move toward presumed consent to increase deceased organ donation rates. However, there remains a paucity of literature on public attitude and barriers regarding the opt-out system, with existing studies limited to Western nations. Therefore, this study aimed to understand public sentiment and different barriers toward organ donation from the perspective of Singapore, a highly diverse and multiethnic Asian society. Methods: A cross-sectional community semi-structured interview was conducted in a public housing estate in Singapore. Pilot test was undertaken before participants were interviewed face-to-face by trained personnel. All statistical evaluations were conducted using Stata. The χ2-test compared subgroups based on patient characteristics while multivariable logistic regression identified predictors of willingness to donate/ assent. Effect estimates were quantified using odds ratio (OR). Findings: Out of 799 individuals, 85% were agreeable to organ donation after death and 81% were willing to assent to donations of family members' organs, which declined by 16% (p < 0.001) after a clinical scenario was presented. Demographic factors including ethnicity, education, marital, and employment status affected willingness to donate and assent. Knowledge correlated significantly with willingness to donate and assent. In particular, knowledge regarding brain death irreversibility had the strongest correlation (AOR 2.15; 95% CI 1.60-2.89). Conclusions: Organ donation rates remain low albeit presumed consent legislation, due to patient-level barriers, including but not limited to knowledge gaps, cultural values, religious backgrounds, and emotional impact at relatives' death. To effectively boost donor rates, it is crucial for policy makers to invest in public education and improve transplant provisions and family protocols.

Selection and Short-Term Outcomes of Living Kidney Donors in Singapore - An Analysis of the Donor Care Registry

<p><b>INTRODUCTION</b>Transplant rates in Singapore have been falling and there is limited information on baseline characteristics and clinical outcomes of living kidney donors nationally. This study aimed to determine the safety of living kidney donor transplant in Singapore by exploring the proportion of donors that meets international selection guidelines and describing short-term clinical outcomes.</p><p><b>MATERIALS AND METHODS</b>We analysed 472 donors who underwent nephrectomies from 1 January 2010 to 31 December 2014 from the Donor Care Registry. We described donor characteristics against 5 international guidelines and measured post-nephrectomy outcomes in 150 local donors for up to 24 months. A multivariate analysis was performed to determine the baseline variables associated with poorer outcomes.</p><p><b>RESULTS</b>There were more foreign than local donors, with differences in gender and hospital types. Selection was generally aligned with international recommendations although 3.0% (using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation) to 8.5% (using radionuclide and creatinine clearance methods) of donors had inappropriate baseline estimated glomerular filtration rates (eGFR) forage. Post-procedure, many foreign donors were lost to follow-up. Over 24 months, eGFR decreased by 33.8% from baseline before recovering gradually to 29.6%. During this period, only 2 donors were admitted for renal or urological conditions and there were no cases of end-stage renal failure or deaths. A lower baseline eGFR (HR: 1.05; 95% Cl, 1.02 to 1.09) and older age (HR: 1.04; 95% Cl, 1.00 to 1.08) were associated with a post-nephrectomy eGFR of less than 60 mL/kg/1.73 m.</p><p><b>CONCLUSION</b>Kidney donation is safe in Singapore. Donor selection is in keeping with international guidelines and short-term outcomes are comparable to other cohorts.</p>

Prevalence of chronic kidney disease-mineral and bone disorder in incident peritoneal dialysis patients and its association with short-term outcomes

<p><b>INTRODUCTION</b>A complex relationship exists between chronic kidney disease-mineral and bone disorder (CKD-MBD) and adverse outcomes among dialysis patients. This study aimed to report the prevalence of CKD-MBD and examine the impact of achieving target CKD-MBD parameters on morbidity and mortality one year after peritoneal dialysis (PD) initiation.</p><p><b>METHODS</b>In this retrospective cohort study, patients electively initiated on PD were followed up for one year. Laboratory parameters were collected and the prevalence of CKD-MBD 4-6 months after PD initiation was determined based on the Kidney Disease Outcomes Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Linear regression and Cox proportional hazards model were used to evaluate the effects of achieving CKD-MBD targets 4-6 months after PD initiation on hospitalisation, the incidence of peritonitis or exit-site infections (ESIs), and mortality at one year.</p><p><b>RESULTS</b>The prevalence of CKD-MBD among the 86 patients in this study was 86.0% (KDOQI) and 54.7% (KDIGO). There was no significant difference in hospitalisation duration between patients who achieved targets and those who did not. Patients who failed to meet all the KDIGO CKD-MBD or calcium serum targets had a higher incidence of peritonitis or ESI. A trend toward shorter time to death was observed among patients who failed to meet the KDIGO phosphorus serum targets.</p><p><b>CONCLUSION</b>There was moderate (KDIGO) to high prevalence (KDOQI) of CKD-MBD among the patients. Achievement of all the KDIGO CKD-MBD or calcium serum targets was associated with reduced peritonitis or ESI, while achievement of the KDIGO phosphorus serum targets was associated with improved survival.</p>

Aliskiren and losartan trial in non-diabetic chronic kidney disease.

INTRODUCTION: This is a report of a clinical trial on the therapeutic efficacy and safety of combined aliskiren and losartan (an angiotensin II receptor blocker (ARB)) versus aliskiren alone and ARB alone in non-diabetic chronic kidney disease (CKD) over a 3-year period. MATERIALS AND METHODS: This was a randomised trial in 155 patients with non-diabetic CKD comparing aliskiren (150 mg/day) (n=52) versus losartan (100 mg/day) (n=52) and the third group aliskiren (150 mg/day) combined with losartan (100 mg/day) (n=51). The trial utilised primary renal end points of eGFR <15 ml/min or end-stage renal failure. RESULTS: All three groups had significant reduction of proteinuria (p<0.001 for all). The changes in eGFR, total urinary protein from baseline to each year were not significantly different between the three therapeutic groups. CONCLUSION: This study in non-diabetic CKD patients showed that combination therapy with aliskiren and ARB was as efficacious as aliskiren alone and ARB alone. There was one patient who developed a non-fatal stroke in the combined aliskiren and ARB group while the other two groups had none.

A retrospective Aliskiren and Losartan study in non-diabetic chronic kidney disease.

AIM: To assess the efficacy of combined Aliskiren and Losartan vs high dose Losartan and Aliskiren alone in chronic kidney disease (CKD). METHODS: This is a retrospective study of 143 patients with non-diabetic CKD comparing combined Aliskiren (150 mg/d) with Losartan (100 mg/d) therapy vs High dose Angiotensin receptor blockers (ARB) (Losartan 200 mg/d) and the third group Aliskiren (150 mg/d) alone. This study involved only patient medical records. Entry criteria included those patients who had been treated with the above drugs for at least 36 mo within the 5 years period; other criteria included proteinuria of 1 g or more and or CKD Stage 3 at the start of the 36 mo period. The study utilised primary renal end points of estimated Glomerular Filtration Rate (eGFR) < 15 mL/min or end stage renal failure. RESULTS: Patients treated with high dose ARB compared to the other two treatment groups had significantly less proteinuria at the end of 36 mo (P < 0.007). All 3 groups had significant reduction of proteinuria (P < 0.043, P < 0.001). Total urinary protein was significantly different between the 3 groups over the 3-year study period (P = 0.008), but not eGFR. The changes in eGFR from baseline to each year were not significantly different between the 3 therapeutic groups (P < 0.119). There were no significant differences in the systolic and diastolic blood pressure between the 3 drug groups throughout the 3 years. The incidence of hyperkalemia (> 5.5 mmol/L) was 14.2% (7/49) in the Combined Aliskiren and ARB group, 8.7% (4/46) in the Aliskiren alone group and 6.3% (3/48) in the High dose ARB group (P < 0.001). CONCLUSION: This study in non-diabetic CKD patients showed that Combination therapy with Aliskiren and ARB was effective but was not safe as it was associated with a high prevalence of hyperkalaemia.

Organ trafficking and transplant tourism: the role of global professional ethical standards-the 2008 Declaration of Istanbul.

By 2005, human organ trafficking, commercialization, and transplant tourism had become a prominent and pervasive influence on transplantation therapy. The most common source of organs was impoverished people in India, Pakistan, Egypt, and the Philippines, deceased organ donors in Colombia, and executed prisoners in China. In response, in May 2008, The Transplantation Society and the International Society of Nephrology developed the Declaration of Istanbul on Organ Trafficking and Transplant Tourism consisting of a preamble, a set of principles, and a series of proposals. Promulgation of the Declaration of Istanbul and the formation of the Declaration of Istanbul Custodian Group to promote and uphold its principles have demonstrated that concerted, strategic, collaborative, and persistent actions by professionals can deliver tangible changes. Over the past 5 years, the Declaration of Istanbul Custodian Group organized and encouraged cooperation among professional bodies and relevant international, regional, and national governmental organizations, which has produced significant progress in combating organ trafficking and transplant tourism around the world. At a fifth anniversary meeting in Qatar in April 2013, the DICG took note of this progress and set forth in a Communiqué a number of specific activities and resolved to further engage groups from many sectors in working toward the Declaration's objectives.

Genomics and disease progression in IgA nephritis.

Apart from clinical, histological and biochemical indices, genomics are now being employed to unravel the pathogenetic mechanisms in the disease progression of IgA nephritis (IgAN). The results of angiotensin converting enzyme (ACE) gene polymorphism have been controversial. Those patients with the DD genotype seem to have a poorer prognosis. However, with high dose angiotensin receptor blocker (ARB) therapy, the ACE gene polymorphism status of a patient may no longer be a matter for concern as those with the DD genotype would also respond favourably to high dose ARB therapy. Association studies with gene sequencing and haplotypes have suggested that multiple genes are involved in the pathogenesis of IgAN. Some workers have reported a synergistic effect in the combined analysis of AGT-M235T and ACE I/D polymorphism. With the use of deoxyribo nucleic acid (DNA) microarray, tens of thousands of gene expressions genome-wide can be examined together simultaneously. A locus of familial IgAN has been described with strong evidence of linkage to IgAN1 on chromosome 6q22-23. Two other loci were reported at 4q26-31 and 17q12-22. DNA microarray techniques could also help in the identification of specific pathogenic genes that are up- or down-regulated and this may allow genome wide analyses of these genes and their role in the pathogenesis and progression of IgAN. Recently, using genome-wide association studies (GWAS) more loci for disease susceptibility for IgAN have been identified at 17p13, 8p23, 22q12, 1q32 and 6p21.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012).

INTRODUCTION: This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries. MATERIALS AND METHODS: The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population. RESULTS: In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%. DISCUSSION: The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD. CONCLUSION: The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.

Global evolutionary trend of the prevalence of primary glomerulonephritis over the past three decades.

OBJECTIVE: The prevalence of primary glomerulonephritis in Singapore is compared with that of 28 other countries to review changing trends in the evolution of primary glomerulonephritis in Asia and other countries. METHOD: 2,586 renal biopsies in Singapore over the past 3 decades were reviewed and compared with data from 28 other countries. RESULTS: In the 1st decade most Asian countries have mesangial proliferative glomerulonephritis as the most common form of primary glomerulonephritis, and in the 3rd decade there has been a dramatic increase in focal and segmental glomerulosclerosis reflecting aging and obesity in keeping with more developed countries. IgA nephritis remains the commonest glomerulonephritis in many countries. Membranous glomerulonephritis continues to be more prevalent in Western countries while mesangial proliferative glomerulonephritis remains prevalent in many Asian countries. CONCLUSION: Apart from geographical and genetic influences, socioeconomic factors may play a role in the evolution of the biopsy pattern in some countries. Worldwide, the prevalence of focal segmental glomerulosclerosis continues to increase. In third world countries some of the commoner forms of glomerulonephritis are related to infections, in contrast to developed countries where the antigenic exposure may be related to diet, allergens and other industrial agents.