Secondary hyperparathyroidism, weight loss, and longer term mortality in haemodialysis patients: results from the DOPPS

Abstract

Background Wasting is a common complication of kidney failure that leads to weight loss and poor outcomes. Recent experimental data identified parathyroid hormone (PTH) as a driver of adipose tissue browning and wasting, but little is known about the relations among secondary hyperparathyroidism, weight loss, and risk of mortality in dialysis patients. Methods We included 42,319 chronic in-centre haemodialysis patients from the Dialysis Outcomes and Practice Patterns Study phases 2-6 (2002-2018). Linear mixed models were used to estimate the association between baseline PTH and percent weight change over 12 months, adjusting for country, demographics, comorbidities, and labs. Accelerated failure time models were used to assess 12 month weight loss as a mediator between baseline high PTH and mortality after 12 months. Results Baseline PTH was inversely associated with 12 month weight change: 12 month weight loss >5% was observed in 21%, 18%, 18%, 17%, 15%, and 14% of patients for PTH ≥600 pg/mL, 450-600, 300-450, 150-300, 50-150, and <50 pg/mL, respectively. In adjusted analyses, 12 month weight change compared with PTH 150-299 pg/mL was À0.60%, À0.12%, À0.10%, +0.15%, and +0.35% for PTH ≥600, 450-600, 300-450, 50-150, and <50 pg/mL, respectively. This relationship was robust regardless of recent hospitalization and was more pronounced in persons with preserved appetite. During follow-up after the 12 month weight measure [median, 1.0 (interquartile range, 0.6-1.7) years; 6125 deaths], patients with baseline PTH ≥600 pg/mL had 11% [95% confidence interval (CI), 9-13%] shorter lifespan, and 18% (95% CI, 14-23%) of this effect was mediated through weight loss ≥2.5%. Conclusions Secondary hyperparathyroidism may be a novel mechanism of wasting, corroborating experimental data, and, among chronic dialysis patients, this pathway may be a mediator between elevated PTH levels and mortality. Future research should determine whether PTH-lowering therapy can limit weight loss and improve longer term dialysis outcomes.

Emerging cross-talks between chronic kidney disease–mineral and bone disorder (CKD–MBD) and malnutrition–inflammation complex syndrome (MICS) in patients receiving dialysis

“…Regarding PTH, a basic study recently showed that persistent higher circulating PTH levels in CKD induce a phenotypic change of white adipose tissue to brown adipose tissue via PTH receptor 1, increase energy expenditure in mice, and also cause muscle atrophy by unknown mechanisms [75]. These data were confirmed by an observational study showing that hemodialysis patients with high serum PTH levels are likely to develop bodyweight loss [23]. These findings collectively suggest that uncontrolled secondary hyperparathyroidism (SHPT) makes a substantial contribution to PEW, frailty, and cachexia in patients with CKD, especially those on dialysis therapy.…”

“…Notably, through advances in our understanding of CKD-MBD pathogenesis, the concept of CKD-MBD continues to evolve and the boundaries of CKD-MBD are expanding to cover a wider range of diseases. Based on recent reports [14,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], the complications considered to be associated with CKD-MBD include a variety of pathologies, such as dementia, anemia, secondary hyperparathyroidism, ventricular hypertrophy, valvular and vascular calcification, heart failure, arrhythmia, constipation, renal inflammation and fibrosis, hepatic inflammation, sarcopenia, malnutrition, malignancy, infection, and fractures (Fig. 1).…”

The impact of weight change and measures of physical functioning on mortality

“…The English Longitudinal Study of Aging by Hamer et all of 6864 men and women with mean age of 66 years found that in lower grip strength was associated with higher all‐cause mortality within each BMI category 12 . Looking at the hazard ratios in the lowest handgrip groups for this cohort for mortality, there was no statistical difference between participants with normal BMI, overweight, or obesity, but for those who lost weight there was higher mortality and also higher mortality if grip strength decreased 10 . A study of 10,088 females and 8616 males from 12 countries by Wang et al (follow up of 9.4 years) showed that obesity and physical inactivity were related to decline in grip strength 13 .…”

Prognosefaktoren bei älteren Dialysepatienten beachten

“…B. kognitive Einschränkungen oder Multimorbidität) nicht in die Messungen einfließen 47 – 51 . Neueste Daten der DOPPS-Studie (DOPPS: Dialysis Outcomes and Practice Patterns Study) etablieren den sekundären Hyperparathyreoidismus als neuen Mechanismus für eine Sarkopenie mit erhöhter Mortalität bei Dialysepatienten 52 , sodass sich hier eine weitere Überlappung zwischen dem urämischen Phänotyp und dem Konzept für Gebrechlichkeit abzeichnet.…”

“…B. kognitive Einschränkungen oder Multimorbidität) nicht in die Messungen einfließen[47][48][49][50][51]. Neueste Daten der DOPPS-Studie (DOPPS: Dialysis Outcomes and Practice Patterns Study) etablieren den sekundären Hyperparathyreoidismus als neuen Mechanismus für eine Sarkopenie mit erhöhter Mortalität bei Dialysepatienten[52], sodass sich hier eine weitere Überlappung zwischen dem urämischen Phänotyp und dem Konzept für Gebrechlichkeit abzeichnet.In einer groß angelegten internationalen Registerarbeit konnte gezeigt werden, dass die Parameter intradialytische Gewichtszunahme, systolischer arterieller Druck, Serum-Albumin-Konzentrationen und C-reaktives Protein (CRP) bereits bis zu einem Jahr im Voraus die bevorstehende Mortalität ankündigen[53]. Auch moderne Peptidbiomarker wie Troponine und NT-proBNP ("N-terminal proB-type natriuretic peptide") korrelieren gut mit dem Eintritt einer terminalen Niereninsuffizienz bei Patienten mit chronischer Nierenerkrankung und mit der Mortalität bei Hämodialysepatienten.…”