Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective post-mortem study

The histological prevalence of beta-2 microglobulin amyloidosis (A beta 2m) was evaluated in a prospective study of joint samples obtained at autopsy in 54 patients on hemodialysis (HD) for 2 to 163 (median 47) months, aged 20 to 80 (median 63) years at HD onset. Carpal tunnel syndrome surgery or radiological signs of A beta 2m were present in 2 and 4% of them, respectively. A control group of 34 patients without end-stage renal disease, autopsied during the same period was used as a reference. The 153 sampled joints (1 to 8, median 2 per patient) were sternoclavicular joints (N = 77), shoulders (N = 35), knees (N = 28), others (N = 13). A beta 2m was diagnosed (positive Congo red with typical birefringence and positive immunostaining of deposits for beta 2m) in 26 of 54 (48%) patients. Prevalence reached respectively 21%, 33%, 50%, 90% and 100% within two years, after 2 to 4 years, 4 to 7 years, 7 to 13 years and more than 13 years HD. The calculated sensitivity of the various joints for A beta 2m detection is significantly higher (P < 0.03) for sternoclavicular joints (97%) and knees (91%) than for shoulders (57%). Multivariate stepwise logistic regression with discriminant analysis identified both HD duration (P = 0.0008) and age at HD onset (P = 0.0093) but not diabetic nephropathy (P = 0.23) or gender (P = 0.25) as independent risk factors for A beta 2m. The probability of joint A beta 2m was quantitated as a function of age and HD duration. In conclusion, A beta 2m may be observed in the large joints early after HD onset. Overall prevalence reaches 48% of the patients on HD for a median of 47 months. It is much higher than that reported on the basis of clinical or radiological evidence. The sternoclavicular and knee joints are more frequently (P < 0.03) involved than the shoulder. The easily accessible sternoclavicular joint therefore appears to be the best site for the early detection of A beta 2m. Both HD duration and age at HD onset, but not diabetic nephropathy, are independent risk factors for A beta 2m

Representative sample of flow cytometric evaluation of the CD14 and CD16 expression on isolated monocytes from a healthy control (left panel) and a hemodialysis patient (right panel).

<p>According to the CD14 and CD16 fluorescence intensity three gates are drawn containing the CD14⁺⁺CD16^-, the CD14⁺⁺CD16⁺ and the CD14⁺CD16⁺⁺ monocyte subpopulations respectively. Hemodialysis patients show a decreased proportion of CD14⁺⁺CD16^- and an increase of CD14⁺⁺CD16⁺ and CD14⁺CD16⁺⁺ monocytes.</p

Quantitative RT-PCR data for CD16 mRNA expression (A) and CX3CR1 mRNA expression (B) in the 4 study groups; control (n = 9), CVE (n = 10), CKD5HD (n = 10), CKD5HD/CVE (n = 10).

<p>* p < 0.05, ** p < 0.01 vs. control; ° p < 0.05, °° p < 0.01 vs. CVE.</p

Control of the purity in the consecutive steps of the isolation procedure of monocytes.

<p>Whole blood (A); peripheral blood mononuclear cells isolated after density gradient centrifugation (B); monocytes (C) and lymphocytes (D) isolated by MACS CD14 microbeads.</p

Subject characteristics.

<p>Values reported are mean ± SEM when normally distributed, otherwise median and range (in parentheses) are given.</p><p>*** <i>p</i> < 0.001</p><p>** <i>p</i> < 0.01</p><p>* <i>p</i> < 0.05 vs. control</p><p>^°°°<i>p</i> < 0.001</p><p>^°°<i>p</i> < 0.01</p><p>^°<i>p</i> < 0.05 vs. CVE</p><p>No significant differences were found between CKD5HD and CKD5HD/CVE.</p><p>Abbreviations: CVE: patients with eGFR > 60 mL/min/1.73m² and a history of cardiovascular event; CKD5HD: hemodialysis patients without previous cardiovascular event; CKD5HD/CVE: hemodialysis patients with a previous cardiovascular event; CRP: C-reactive protein; GFR: glomerular filtration rate; NA: not applicable</p><p>Subject characteristics.</p

Percentages and absolute numbers of CD14⁺⁺CD16^-, CD14⁺⁺CD16⁺ and CD14⁺CD16⁺⁺ monocyte subsets in studied subjects.

<p>MFI: mean fluorescence intensity</p><p>**P<0.01</p><p>*P<0.05 vs control</p><p>°°p<0.01</p><p>°P<0.05 vs CVE</p><p>Percentages and absolute numbers of CD14⁺⁺CD16^-, CD14⁺⁺CD16⁺ and CD14⁺CD16⁺⁺ monocyte subsets in studied subjects.</p

List of differentially expressed genes in the comparison CKD5HD/CVE vs CVE but not in the comparison CVE vs control by the custom cDNA array in isolated monocytes with a fold-change ≥ 2.0 and a p-value ≤ 0.01.

<p>List of differentially expressed genes in the comparison CKD5HD/CVE vs CVE but not in the comparison CVE vs control by the custom cDNA array in isolated monocytes with a fold-change ≥ 2.0 and a p-value ≤ 0.01.</p

Priority topics for European multidisciplinary guidelines on the management of chronic kidney disease in older adults

PURPOSE: To identify and prioritize potential topics to be addressed in the development of European multidisciplinary guidelines on the management of chronic kidney disease stage 3b-5 in older patients. METHODS: We composed a list of 47 potential guideline topics by reviewing the literature, consulting online 461 nephrologists and 107 geriatricians, and obtaining expert input. A multidisciplinary panel of twelve experts then prioritized the topics during a face-to-face consensus meeting, following a nominal group technique structure with two voting rounds. Topics were rated on a 9-point scale ranging from 1 ('not at all important') to 9 ('critically important'). RESULTS: The highest rating (median; range) was assigned to 'Screening and referral' (8.5; 2.0). Eight topics shared the second highest rating with a median priority score of 8.0 (2.0) and included 'Starting dialysis or not' and 'Accurate assessment of renal function.' 'Targets for and treatment of diabetes' received the lowest rating with (3.0; 6.0). CONCLUSIONS: This joint initiative of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA) and the European Union Geriatric Medicine Society (EUGMS) prioritized the development of guidance on interdisciplinary referral of older patients with chronic kidney disease stage 3b-5. Future guidance will therefore focus on identifying prognostic scores to predict death and progression to end-stage renal disease, as well as accurate tests for assessment of renal function in older kidney patients. This will contribute to more informed treatment decision making in this growing patient population

Epidemiology of native kidney disease in Flanders : results from the FCGG kidney biopsy registry

Background The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders. Methods From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included. A 'double diagnostic coding' strategy was used, in which every biopsy sample received a histopathological and final clinical diagnosis. Frequency distribution and incidence rate of both diagnoses were reported and compared with other European registries. Results The median age at biopsy was 61.1 years (interquartile range, 46.1-71.7); male patients were more prevalent (62.1%) and biopsy incidence rate was 129.3 per million persons per year. Immunoglobulin A nephropathy was the most frequently diagnosed kidney disease (355 biopsies, 17.3% of total) with a similar frequency as in previously published European registries. The frequency of tubulointerstitial nephritis (220 biopsies, 10.7%) and diabetic kidney disease (154 biopsies, 7.5%) was remarkably higher, which may be attributed to changes in disease incidence as well as biopsy practices. Discordances between histopathological and final clinical diagnoses were noted and indicate areas for improvement in diagnostic coding systems. Conclusions The FCGG registry, with its 'double diagnostic coding' strategy, provides useful population-based epidemiological data on a large Western European population and allows subgroup selection for future research