Disease recurrence in paediatric renal transplantation

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7–8%, mainly due to primary glomerulonephritis (70–80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14–50% DR, 40–60% GL; atypical haemolytic uraemic syndrome 20–80% DR, 10–83% GL; membranoproliferative glomerulonephritis 30–100% DR, 17–61% GL; membranous nephropathy ∼30% DR, ∼50% GL; lipoprotein glomerulopathy ∼100% DR and GL; primary hyperoxaluria type 1 80–100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36–60% DR, 7–10% GL; systemic lupus erythematosus 0–30% DR, 0–5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules

Predictors of quality of life in patients with end-stage renal disease on hemodialysis

Marc M Saad,1 Youssef El Douaihy,1 Christine Boumitri,1 Chetana Rondla,2 Elias Moussaly,1 Magda Daoud,1 Suzanne E El Sayegh3 1Internal Medicine, Staten Island University Hospital, Staten Island, NY, 2Nephrology, Emory University Hospital, Atlanta, GA, 3Nephrology, Staten Island University Hospital, Staten Island, NY, USA Background: Assessment of quality of life (QOL) of end-stage renal disease (ESRD) patients (physical, mental, and social well-being) has become an essential tool to develop better plans of care. Objective of this study is to determine which demographic and biochemical parameters correlate with the QOL scores in patients with ESRD on hemodialysis (HD) using Kidney Disease QOL-36 surveys (KDQOL). Methods: A retrospective chart review of all ESRD patients who underwent HD at an outpatient center. The five components of the KDQOL were the primary end points of this study (burden of kidney disease, symptoms and problems, effects of kidney disease on daily life, mental component survey, and physical component survey). Scores were grouped into three categories (below average, average, and above average). In addition to demographics (age, sex, and race), the independent variables such as weight gain, number of years on dialysis, urea reduction ratio, calcium, phosphorus, parathyroid hormone, albumin, and hemoglobin in the serum were collected. Chi-square analysis for dependent variables and the nominal independent variables was used, and analysis of variance analysis was used for continuous independent variables. Ordinal regression using PLUM (polytomous universal model) method was used to weigh out possible effects of confounders. Results: The cohort size was 111 patients. Mean age was 61.8 (±15.5) years; there were more males than females (64.9% vs 35.1%), the mean time-on-dialysis at the time of the study was 4.3 (4.8) years. Approximately two-thirds of the responses on all five domains of the questionnaire ranked average when compared to the national numbers. The remainders were split between above average (20.6%) and below average (13.4%). In our cohort, no relationships were statistically significant between the five dependent variables of interest and the independent variables by chi-square- and t-test analyses. This was further confirmed by regression analysis. Of note, sex carried the strongest statistical significance (with a P-value of 0.16) as a predictor of “the burden of kidney disease on daily life” in ordinal regression. Conclusion: Prior studies have shown variables such as serum phosphate level, intradialytic weight gain, and dialysis adequacy are associated with lower KDQOL scores; however, this was not evident in our analysis likely due to smaller sample size. Larger size studies are required to better understand the predictors of QOL in ESRD patients on HD. Keywords: quality of life, end-stage renal disease, hemodialysis, metabolic profil

The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk–outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01–4·94) deaths and 105 million (95·0–116) DALYs for both sexes combined, representing 44·4% (41·3–48·4) of all cancer deaths and 42·0% (39·1–45·6) of all DALYs. There were 2·88 million (2·60–3·18) risk-attributable cancer deaths in males (50·6% [47·8–54·1] of all male cancer deaths) and 1·58 million (1·36–1·84) risk-attributable cancer deaths in females (36·3% [32·5–41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6–28·4) and DALYs by 16·8% (8·8–25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9–42·8] and 33·3% [25·8–42·0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Funding Bill & Melinda Gates Foundation