Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study.

OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥ 18 years, CKD stage 3-5 non dialysis, Sbicar < 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 ± 287 pg/mL, and mean serum Sbicar was 19.3 ± 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 ± 2.9 mmol/L, P < .001) and 4 weeks (23.4 ± 1.9 mmol/L, P < .001). There was no change in serum Klotho at two (630 ± 333 mmol/L) and 4 weeks (632 ± 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 ± 31.6 pg/mmoL), increased by 320% at two weeks (P < .005) and by 280% at 4 weeks (P < .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.

In Hemodialysis Patients, Intradialytic Resistance Exercise Improves Osteoblast Function: A Pilot Study.

OBJECTIVE: Abnormalities in mineral and bone metabolism are frequent in chronic kidney disease patients. Physical exercise can improve many indicators of physical functioning, and recent studies showed beneficial effects on bone mineral density in the general population. The aim of this study was to evaluate the effects of resistance exercise training on bone markers and body composition in hemodialysis (HD) patients. DESIGN: This was a randomized controlled trial. SUBJECTS: The study included 13 HD patients (46.2% men). INTERVENTION: Patients were divided into a control group and an exercise group, which performed 8 weeks of intradialytic resistance exercise. Serum sclerostin, bone alkaline phosphatase (BAP), insulin, leptin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and body composition were measured before and after the exercise period. RESULTS: In the exercise group, BAP levels increased from 11.4 ± 6.5 to 14.6 ± 6.4 U/L (P < .05) and serum 1,25-dihydroxyvitamin D levels from 46.0 ± 23.5 to 87.2 ± 31.8 ng/mL (P < .05). After exercise, serum BAP levels were inversely correlated with serum sclerostin (r = -0.96, P < .05). There was no change in body composition in either group. CONCLUSION: Resistance exercise training appears to be an interesting approach for stimulating BAP production in HD patients and may prevent bone loss and stimulate bone formation.

In chronic kidney disease, serum α-Klotho is related to serum bicarbonate and proteinuria.

OBJECTIVES: Klotho is an "aging-suppressor" gene and encodes a single-pass transmembrane protein predominantly expressed in renal tubules. Whether chronic kidney disease (CKD) affects serum Klotho is poorly documented. We aimed to measure the relationship of serum α-Klotho with renal function, acid-base status, bone biomarkers, and proteinuria in CKD patients. DESIGN SETTING, PARTICIPANTS, AND MEASUREMENTS: We measured serum α-Klotho, serum FGF23, and glomerular filtration rate by inulin clearance in 60 CKD patients between January and July 2011. We also measured serum creatinine, bicarbonate, calcium, phosphorus, parathyroid hormone, C-reactive protein, and 25-OH vitamin D. Proteinuria was obtained from a 24-h urine collection. RESULTS: The median serum α-Klotho was 478 (348-658) pg/mL. We found an inverse relationship between serum α-Klotho and serum creatinine (r = -0.36, P = .007), proteinuria (r = -0.36, P = .013), and a positive relationship with serum bicarbonate (r = 0.33, P = .011). There was no further significant relation between serum α-Klotho and inulin clearance or serum FGF23. Multiple regression analysis including serum bicarbonate, serum creatinine, and proteinuria indicated that only serum bicarbonate was associated with serum α-Klotho (P = .003). CONCLUSIONS: This study shows that in CKD, serum α-Klotho is related to serum bicarbonate and proteinuria and not to renal function. Further research is required to determine whether correcting these 2 amenable conditions would improve serum α-Klotho.

Factors predictive of anti-spike antibody titers after COVID-19 vaccination in hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients have a high prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and mortality, but they may have a weak response to coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: This study aimed to evaluate factors predictive of humoral response in HD patients vaccinated against SARS-CoV-2 infection. MATERIAL AND METHODS: This is a 2-center observational study including HD patients who received the BNT162b2 mRNA vaccine followed by serological measurements 20 days and 4 weeks after the 1st and 2nd dose, respectively. Healthy controls were included. Anti-spike antibody was measured using the chemiluminescent immunoassay (CLIA) method. The quantile regression analysis was performed to assess factors associated with anti-spike antibody titers. RESULTS: Seventy-two HD patients and 22 healthy controls were included. Mean age of dialysis patients and controls was 72.5 ±11.5 years and 45.7 ±17.4 years, respectively. In the HD group, median levels of anti-spike antibody were 3 (interquartile range (IQR): 0.5-26) UI/mL and 391 (IQR: 55-1642) UI/mL after the 1st and 2nd dose, respectively, with response rates of 62.5% and 96.7%. The median level of the anti-spike antibody after the 1st dose in previously infected patients was 8571 (IQR: 2586-19147) UI/mL. There was a significant correlation between anti-spike antibody levels after the 2nd dose and age and anti-hepatitis B surface (HBs) antibody and serum albumin levels (Spearman's rho: r = -0.289, p < 0.001; r = 0.357, p = 0.027; r = 0.317; p = 0.026, respectively). The regression analysis showed a significant association of previous infection and anti-Hbs antibody level with anti-spike antibody level after the 1st dose of vaccine (p < 0.001). After a 5-month follow-up, 2 vaccinated patients contracted COVID-19. CONCLUSIONS: This study showed a response rate of 96.7% to 2 doses of BNT162b2 mRNA vaccine in HD patients and 100% to a single dose in previously infected patients. The level of anti-spike antibody can be predicted by age, anti-Hbs antibodies, serum albumin, and previous infection. Despite the immunization of patients, preventive measures should be maintained in all dialysis units.

Musculoskeletal disorders in hemodialysis patients: different disease clustering according to age and dialysis vintage.

Musculoskeletal disorders remain a major problem in hemodialysis patients. The aim of the study was to estimate the prevalence of musculoskeletal manifestations in hemodialysis patients and identify disease cluster profiles. We performed a cross-sectional study including all adult patients in the hemodialysis unit at Hotel-Dieu de France Hospital. We collected demographic characteristics, musculoskeletal symptoms, biologic parameters, and treatments. Musculoskeletal disorders were classified by a rheumatologist into predefined diagnostic categories. Prevalence was presented, and a cluster analysis was performed. Eighty-nine patients were included, mean age was 67.5 ± 12 years, and 43.8% were female. Dialysis vintage was 5.7 ± 5.37 years. Musculoskeletal symptoms were reported by 76.4% of the patients. Pain was the most frequent symptom (44.9%). The main diagnoses were osteoarthritis (53.9%) and fracture (27%). Musculoskeletal symptoms and disorders were significantly associated with dialysis vintage and age. Cluster analysis identified three patient profiles: younger with low calcium levels, younger but long dialysis vintage with osteoarthritis and carpal tunnel syndrome, and older with long dialysis vintage and fractures. The prevalence of musculoskeletal manifestations is high in the hemodialysis population and increases with dialysis vintage. Musculoskeletal disorders cluster according to age and dialysis vintage. Key Points• Musculoskeletal symptoms are highly prevalent among hemodialysis patients (76.4%).• All musculoskeletal disorders are associated with dialysis vintage and age.• Three clusters are identified among hemodialysis patients: young with low calcium levels, young but long dialysis vintage with osteoarthritis and carpal tunnel syndrome and old with long dialysis vintage with fractures.

Incidence of Donor-Specific Anti-HLA Antibodies in Non-HLA-Sensitized Patients Given Tacrolimus Once or Twice Daily During the First 2 Years After Kidney Transplant.

OBJECTIVES: Antibody-mediated rejection is a main cause of long-term kidney allograft loss. Nonad-herence and tacrolimus intrapatient variability have been identified as risk factors for developing de novo donor-specific antibodies. Tacrolimus, given once daily, can improve adherence and reduce variabilities among patients. The aim of this retrospective observational study was to compare the incidences of donor-specific antibodies at 2 years posttransplant in de novo kidney transplant recipients given tacrolimus either once or twice daily. MATERIALS AND METHODS: Non-HLA sensitized de novo kidney-transplant recipients given tacrolimus either once daily (n = 82) or twice daily (n = 168), combined with mycophenolic acid with or without steroids, were included in the study. All patients were screened for anti-HLA antibodies before transplant, at 6, 12, and 24 months posttransplant, and each time the patient presented with impaired kidney function. RESULTS: The 2-year incidence of donor-specific antibodies was 2.8%. During the follow-up period, 6 patients (3.6%) receiving tacrolimus twice daily and one patient (1.2%) receiving tacrolimus once daily developed a donor-specific antibody (P = .43). The incidence of antibody-mediated rejection was 4.8% under tacrolimus once daily and 2.7% under tacrolimus twice daily (P = .5). Tacrolimus intrapatient variability was similar with both formulations and was not associated with development of donor-specific antibodies. CONCLUSIONS: The use of tacrolimus-based immunosup-pression associated with mycophenolic acid was associated with a low risk of de novo donor-specific antibodies. After 2 years, the incidence of de novo donor-specific antibodies did not differ significantly between patients treated with tacrolimus once daily versus those treated with the twice-daily formulation.

Successful Transplantation in ABO- and HLA-Incompatible Living Kidney Transplant Patients: A Report on 12 Cases.

Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m2 ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption). By day 0, 17 of the 27 DSAs had become undetectable. After 19 (3-51) months, patient- and graft-survival rates were 100% and 91.6%, respectively. One patient had an acute humoral rejection whereas three had a chronic antibody-mediated rejection (CAMR). At the last follow-up, kidney biopsies were nearly normal in seven cases (58.3%) and renal function was excellent except for the three cases of CAMR. Four patients had a BK virus infection. We conclude that ABOi/HLAi living-kidney transplantation is a reasonable option for highly sensitized patients.