bims-fikidi Biomed News
on Fibroblast growth factor 23 in chronic kidney disease
Issue of 2018–06–03
ten papers selected by
Regina Goetz, New York University Langone Medical Center
  1. [Novel hormones related to the calcium and phosphate homeostasis in kidney disease].
  2. Personalized dynamic risk assessment in nephrology is a next step in prognostic research.
  3. Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients.
  4. Diastolic blood pressure and risk profile in renal and cardiovascular diseases. Results from the SPRINT trial.
  5. Transplantation Opportunities of Hepatitis C Virus-Seropositive Patients on the Kidney Waiting List.
  6. Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not.
  7. Anthropometry-based Equations to Estimate Body Composition: A Suitable Alternative in Renal Transplant Recipients and Patients With Nondialysis Dependent Kidney Disease?
  8. Renal Function Changes after Percutaneous Nephrolithotomy in Renal Calculi Patients with a Solitary Kidney Compared to Bilateral Kidneys.
  9. Regular monitoring of cytomegalovirus (CMV)-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.
  10. Secondary IgA nephropathy.
  1. Ugeskr Laeger. 2018 May 21. pii: V05170353. [Epub ahead of print]180(21):
    [Novel hormones related to the calcium and phosphate homeostasis in kidney disease].
    Maria Lerche Mace, Klaus Ølgaard, Eva Lewin.
      Calcium and phosphate levels are regulated by a complex interplay between parathyroid hormone (PTH), calcitriol, fibroblast growth factor 23 (FGF23) and its co-receptor αKlotho. Kidney failure causes severe disturbances in the mineral and bone homeostasis resulting in phosphate retention, hypocalcaemia and high plasma levels of FGF23 and PTH, and the patients develop fragile bones and vascular calcifications. Today's treatments aim to lower the levels of phosphate and PTH. Future studies need to clarify, if lowering the FGF23 level or supplementation with αKlotho will improve survival for patients with chronic kidney disease.
  2. Kidney Int. 2018 May 24. pii: S0085-2538(18)30284-9. [Epub ahead of print]
    Personalized dynamic risk assessment in nephrology is a next step in prognostic research.
    Milos Brankovic, Isabella Kardys, Ewout J Hoorn, Sara Baart, Eric Boersma, Dimitris Rizopoulos.
      In nephrology, repeated measures are frequently available (glomerular filtration rate or proteinuria) and linked to adverse outcomes. However, several features of these longitudinal data should be considered before making such inferences. These considerations are discussed, and we describe how joint modeling of repeatedly measured and time-to-event data may help to assess disease dynamics and to derive personalized prognosis. Joint modeling combines linear mixed-effects models and Cox regression model to relate patient-specific trajectory to their prognosis. We describe several aspects of the relationship between time-varying markers and the endpoint of interest that are assessed with real examples to illustrate the aforementioned aspects of the longitudinal data provided. Thus, joint models are valuable statistical tools for study purposes but also may help health care providers in making well-informed dynamic medical decisions.
    Keywords:  individualized prognosis; longitudinal study; personalized dynamic risk assessment; repeated-measures design
    DOI:  https://doi.org/10.1016/j.kint.2018.04.007
  3. Int Urol Nephrol. 2018 May 26.
    Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients.
    Teodor Kacso, Cosmina Ioana Bondor, Crina Claudia Rusu, Diana Moldovan, Dacian Trinescu, Laura Anca Coman, Maria Ticala, Alexandra Maria Gavrilas, Alina Ramona Potra.
       PURPOSE: Adiponectin an adipokine, produced by mature adipocyte, has an important effect on several aspects of endothelial function, including leukocyte adhesion (mediated by adhesion molecules like intercellular adhesion molecule 1 (ICAM1) endothelial cell selective adhesion molecule ESAM). Recently, it has been linked to vascular endothelial growth factor (VEGF)-modulated angiogenesis. ESAM might also be involved in modulating VEGF-dependent actions. We studied relationship of adiponectin to ESAM, ICAM1, and VEGF in type 2 diabetic patients (T2DP) with or without microvascular complications.
    METHODS: Incident T2DP referred for nephrologic evaluation were included (patients with no nephropathy or stage 1-4 nephropathy). T2DP with stage 5 chronic kidney disease (CKD) were selected from a dialysis center. Clinical, standard laboratory assessment and adiponectin, ESAM, ICAM1, and VEGF (ELISA) were recorded.
    RESULTS: Eighty-seven patients were included, 15 had no CKD, 30 with stage 1 or 2 CKD, 20 with stage 3 or 4 CKD and 22 patients on dialysis. ESAM was higher in patients with CKD than in those without CKD (p = 0.02), adiponectin, ICAM1, and VEGF were similar. Adiponectin correlated in univariate analysis to ESAM (r = 0.32, p = 0.002), ICAM1 (r = 0.23, p = 0.038), and CRP (r = 0.31, p = 0.012), and inversely to serum albumin (r = - 0.57, < 0.0001). In predialysis patients, adiponectin also correlated to albuminuria (r = 0.54, p < 0.0001) and glomerular filtration rate (r = - 0.46, p = 0.0001). In multivariate regression ESAM (p = 0.04), VEGF (p = 0.03), and albumin (p < 0.0001) are significant predictors of adiponectin. None of these cytokines were different when comparing patients with and without retinopathy.
    CONCLUSION: Adiponectin is directly linked to adhesion molecules and VEGF in T2DP.
    Keywords:  Adhesion molecule; Adiponectin; Atherogenesis; Chronic kidney disease; Diabetes; ESAM
    DOI:  https://doi.org/10.1007/s11255-018-1890-1
  4. J Am Soc Hypertens. 2018 May 05. pii: S1933-1711(18)30110-4. [Epub ahead of print]
    Diastolic blood pressure and risk profile in renal and cardiovascular diseases. Results from the SPRINT trial.
    Rita Del Pinto, Davide Pietropaoli, Claudio Ferri.
      The Systolic Blood Pressure Intervention Trial (SPRINT) trial demonstrated the efficacy and safety of targeting a systolic blood pressure of <120 mmHg compared to <140 mmHg in selected hypertensive patients. Some evidence, however, suggests a J-curve for; diastolic blood pressure (DBP) particularly in subjects with cardiovascular (CV) and chronic kidney disease. We evaluated the risk of events in SPRINT with focus on these subgroups according to DBP. Mean DBP (±standard deviation) throughout follow-up time was calculated for each patient. Patients were then categorized into five groups according to mean DBP (<60 mmHg, 60-69 mmHg, 70-79 mmHg [reference], 80-89 mmHg, ≥90 mmHg); hazard ratio for outcomes was assessed overall and in the predefined subgroups. A higher risk for CV events was observed in the lower DBP range overall (hazard ratio 1.46, confidential interval 95% 1.1-1.95, P < .001), but not in the absence of pre-existing CV or renal disease. Indeed, such risk significantly increased above 80 mmHg in patients with CV disease and below 70 mmHg in those with chronic kidney disease for selected outcomes. DBP<70 mmHg particularly affected renal outcomes irrespective of renal status. Different risk profiles according to DBP appear to be related to specific clinical characteristics in SPRINT. These findings require further testing in dedicated trials with appropriate follow-up.
    Keywords:  Cardiovascular diseases; chronic renal insufficiency; diastolic blood pressure
    DOI:  https://doi.org/10.1016/j.jash.2018.04.004
  5. Transplant Proc. 2018 Apr 18. pii: S0041-1345(18)30614-6. [Epub ahead of print]
    Transplantation Opportunities of Hepatitis C Virus-Seropositive Patients on the Kidney Waiting List.
    A Oruc, A Ersoy.
       OBJECTIVE: Besides severe organ shortage, hepatitis C virus (HCV) infection is an important obstacle for kidney transplantation because of long waiting times on deceased kidney donor waiting lists. We aimed to evaluate calling number of candidates according to HCV serology.
    METHOD: A total of 404 adults on the deceased donor waiting list invited for cadaveric transplantation was evaluated. Demographic data, waiting time, calling number for transplantation, and viral serology were obtained during the 6-year period.
    RESULTS: Mean waiting duration and calling number of all patients were 42.7 ± 34 months and 1.56 ± 4.37 times, respectively. Twenty-six candidates had chronic HCV infection and 12 of 26 were HCV RNA-positive. Mean waiting duration and calling number in anti-HCV-positive candidates were significantly higher compared with anti-HCV-negative candidates (85.3 ± 38.8 vs 39.8 ± 31.6 months, and 10.8 ± 10.3 vs 0.92 ± 2.6 times, respectively; P < .001). Mean waiting duration and total calling number in HCV-RNA-positive candidates were significantly higher than in HCV-RNA-negative ones (107.5 ± 7.5 vs 66.2 ± 44.8 months; P = .018; 15 ± 9.7 vs 7.3 ± 9.8 times, respectively; P = .026).
    CONCLUSIONS: Chronic HCV infection is an important issue leading to longer waiting time on the list. Our observation showed that waiting durations of anti-HCV-positive candidates were longer than that of negative patients, although they had more frequent opportunity for transplantation.
    DOI:  https://doi.org/10.1016/j.transproceed.2018.04.044
  6. Kidney Int. 2018 May 23. pii: S0085-2538(18)30246-1. [Epub ahead of print]
    Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not.
    Helen Tam-Tham, Robert R Quinn, Robert G Weaver, Jianguo Zhang, Pietro Ravani, Ping Liu, Chandra Thomas, Kathryn King-Shier, Karen Fruetel, Matt T James, Braden J Manns, Marcello Tonelli, Fliss E M Murtagh, Brenda R Hemmelgarn.
      Comparisons of survival between dialysis and nondialysis care for older adults with kidney failure have been limited to those managed by nephrologists, and are vulnerable to lead and immortal time biases. So we compared time to all-cause mortality among older adults with kidney failure treated vs. not treated with chronic dialysis. Our retrospective cohort study used linked administrative and laboratory data to identify adults aged 65 or more years of age in Alberta, Canada, with kidney failure (2002-2012), defined by two or more consecutive outpatient estimated glomerular filtration rates less than 10 mL/min/1.73m2, spanning 90 or more days. We used marginal structural Cox models to assess the association between receipt of dialysis and all-cause mortality by allowing control for both time-varying and baseline confounders. Overall, 838 patients met inclusion criteria (mean age 79.1; 48.6% male; mean estimated glomerular filtration rate 7.8 mL/min/1.73m2). Dialysis treatment (vs. no dialysis) was associated with a significantly lower risk of death for the first three years of follow-up (hazard ratio 0.59 [95% confidence interval 0.46-0.77]), but not thereafter (1.22 [0.69-2.17]). However, dialysis was associated with a significantly higher risk of hospitalization (1.40 [1.16-1.69]). Thus, among older adults with kidney failure, treatment with dialysis was associated with longer survival up to three years after reaching kidney failure, though with a higher risk of hospital admissions. These findings may assist shared decision-making about treatment of kidney failure.
    Keywords:  chronic dialysis; chronic kidney disease; geriatric nephrology; kidney failure; nondialysis care; survival
    DOI:  https://doi.org/10.1016/j.kint.2018.03.007
  7. J Ren Nutr. 2018 May 24. pii: S1051-2276(18)30081-5. [Epub ahead of print]
    Anthropometry-based Equations to Estimate Body Composition: A Suitable Alternative in Renal Transplant Recipients and Patients With Nondialysis Dependent Kidney Disease?
    Thomas J Wilkinson, Danielle Richler-Potts, Daniel G D Nixon, Jill Neale, Alice C Smith.
       OBJECTIVE: Chronic kidney disease (CKD) patients and renal transplant recipients (RTRs) are characterized by aberrant body composition such as muscle wasting and obesity. It is still unknown which is the most accurate method to estimate body composition in CKD. We investigated the validity of the Hume equation and bioelectrical impedance analysis (BIA) as an estimate of body composition against dual-energy X-ray absorptiometry (DXA) in a cohort of nondialysis dependent (NDD)-CKD and RTRs.
    DESIGN AND METHODS: This was a cross-sectional study with agreement analysis of different assessments of body composition conducted in 61 patients (35 RTRs and 26 NDD-CKD) in a secondary care hospital setting in the UK. Body composition (lean mass [LM], fat mass [FM], and body fat% [BF%]) was assessed using multifrequency BIA and DXA, and estimated using the Hume formula. Method agreement was assessed by intraclass correlation coefficient (ICC), regression, and plotted by Bland and Altman analysis.
    RESULTS: Both BIA and the Hume formula were able to accurately estimate body composition against DXA. In both groups, the BIA overestimated LM (1.7-2.1 kg, ICC .980-.984) and underestimated FM (1.3-2.1 kg, ICC .967-.972) and BF% (3.1-3.8%, ICC .927-.954). The Hume formula also overestimated LM (3.5-3.6 kg, ICC .950-.960) and underestimated BF% (1.9-2.1%, ICC .808-.859). Hume-derived FM was almost identical to DXA in both groups (-0.3 to 0.1 kg, ICC .947-.960).
    CONCLUSION: Our results demonstrate, in RTR and NDD-CKD patients, that the Hume formula, whose estimation of body composition is based only upon height, body mass, age, and sex, may reliably predict the same parameters obtained by DXA. In addition, BIA also provided similar estimates versus DXA. Thus, the Hume formula and BIA could provide simple and inexpensive means to estimate body composition in renal disease.
    DOI:  https://doi.org/10.1053/j.jrn.2018.04.003
  8. BJU Int. 2018 May 26.
    Renal Function Changes after Percutaneous Nephrolithotomy in Renal Calculi Patients with a Solitary Kidney Compared to Bilateral Kidneys.
    Xiaolei Shi, Yonghan Peng, Ling Li, Xiao Li, Qi Wang, Wei Zhang, Hao Dong, Rong Shen, Chaoyue Lu, Min Liu, Xiaofeng Gao, Yinghao Sun.
       PURPOSE: To evaluate renal function changes and risk factors of acute kidney injury after percutaneous nephrolithotomy (PCNL) in renal calculi patients with a solitary kidney (SK) or normal bilateral kidneys (BK).
    METHOD: Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. Fifty-three patients with a solitary kidney were paired with fifty-three patients with normal bilateral kidneys via a propensity score-matched analysis. Data regarding the following variables were collected: age, sex, body mass index (BMI), stone size, distribution, operation time, perioperative outcomes and complications. The complications were graded according to a modified Clavien system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting acute kidney injury.
    RESULT: The SK and BK groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and score on the American Society of Anesthesiologists Physical status (ASAPS) classification system. The initial and final stone-free rates (SFRs) were comparable between the SK and BK groups (initial: 52.83% vs 58.49%, P=0.696; final: 84.91% vs 92.45%, P=0.359). The complication rate according to the Clavien system showed no difference between the two groups. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the follow-up to 6 months, eGFR was lower in the SK group than in the BK group. We observed a modest improvement in renal function immediately after PCNL in the BK group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a solitary kidney, preoperative creatinine levels and diabetes were independent risk factors for predicting acute kidney injury post-PCNL.
    CONCLUSION: Considering the overall complication rates, PCNL is mostly a safe procedure to deal with renal calculi among patients with solitary kidneys or normal bilateral kidneys. Follow-up renal function analysis showed a modest improvement in the patients of the two groups. Compared to patients with normal bilateral kidneys, patients with a solitary kidney were inclined to develop acute kidney injury after PCNL. This article is protected by copyright. All rights reserved.
    Keywords:  Acute Kidney Injury; Percutaneous Nephrolithotomy; Renal Calculi; Renal Function; Solitary Kidney
    DOI:  https://doi.org/10.1111/bju.14413
  9. Clin Microbiol Infect. 2018 May 24. pii: S1198-743X(18)30441-5. [Epub ahead of print]
    Regular monitoring of cytomegalovirus (CMV)-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.
    Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI)
       OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-center designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicenter cohort of intermediate-risk kidney transplant (KT) recipients.
    METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction preemptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T-cells were enumerated through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and IE-1 peptides (mean of 6 measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T-cells were calculated at baseline and day 15.
    RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/μL had higher risk of CMV events (adjusted hazard ratio [aHR]: 2.84; P-value = 0.054). When the CMI assessment was performed at the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T-cells/μL (aHR: 2.18; P-value = 0.034) or <1.0 CD4+ T-cells/μL (aHR: 2.43; P-value = 0.016) also predicted the subsequent development of CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T-cells at days 60 and 180 were associated with a higher incidence of late-onset events.
    CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.
    Keywords:  cell-mediated immunity; cytomegalovirus; immune monitoring; intracellular cytokine staining; kidney transplantation
    DOI:  https://doi.org/10.1016/j.cmi.2018.05.010
  10. Kidney Int. 2018 May 24. pii: S0085-2538(18)30245-X. [Epub ahead of print]
    Secondary IgA nephropathy.
    Manish K Saha, Bruce A Julian, Jan Novak, Dana V Rizk.
      IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culminate in the development of primary IgA nephropathy. Whether secondary forms of the disease share common pathways triggered by underlying disorders or different mechanisms leading to similar pathologic findings remains to be determined. In this article we describe the most frequent etiologies for secondary IgA nephropathy and review the available literature for the pathophysiology.
    Keywords:  autoimmune diseases; glomerulonephritis; inflammatory bowel disease; liver disease; post-infectious glomerulonephritis
    DOI:  https://doi.org/10.1016/j.kint.2018.02.030
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