bims-fikidi Biomed News
on Fibroblast growth factor 23 in chronic kidney disease
Issue of 2018–05–13
sixteen papers selected by
Regina Goetz, New York University Langone Medical Center
  1. Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease.
  2. Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy.
  3. Cost-Effectiveness Analysis of Renin-Angiotensin Aldosterone System Blockade in Progression of Chronic Kidney Disease.
  4. Performance of point of care assays for hepatitis B and C viruses in chronic kidney disease patients.
  5. Delayed Recovery of Renal Function After Donor Nephrectomy.
  6. Fibulin-7, a heparin binding matricellular protein, promotes renal tubular calcification in mice.
  7. Complement activation in patients with diabetic nephropathy.
  8. Dexmedetomidine attenuates renal fibrosis via α2-adrenergic receptor-dependent inhibition of cellular senescence after renal ischemia/reperfusion.
  9. Clinical predictive biomarkers for normoalbuminuric diabetic kidney disease.
  10. Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis.
  11. C3 glomerulopathy associated with monoclonal Ig is a distinct subtype.
  12. Bone and mineral metabolism at 55 haemodialysis centres in Lima.
  13. Is the Clinical Outcome Good or Bad in Patients Hospitalized Within 1 Year After Kidney Transplantation?
  14. Kidney-targeted inhibition of protein kinase C-α ameliorates nephrotoxic nephritis with restoration of mitochondrial dysfunction.
  15. Haemodialysis membranes.
  16. On the nature of toenail opacities in renal insufficiency.
  1. J Comp Pathol. 2018 Apr;pii: S0021-9975(18)30040-9. [Epub ahead of print]160 79-83
    Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease.
    R Nakamura, A Yabuki, O Ichii, H Mizukawa, N Yokoyama, O Yamato.
      Renal capillary rarefaction is a crucial event that leads to tubulointerstitial damage during the progression of chronic kidney disease (CKD). In the present study, changes in CD34-positive renal capillaries were investigated in dogs and cats with CKD. A significant decrease in CD34-positive capillaries was observed in canine diseased kidneys, even at the early stage of disease. In cats, CD34-positive capillaries were well preserved in the diseased kidneys, with no link to the severity of CKD. Renal capillary rarefaction might be a trigger event that leads to the progression of CKD in dogs, rather than in cats.
    Keywords:  capillary rarefaction; cat; chronic kidney disease; dog
    DOI:  https://doi.org/10.1016/j.jcpa.2018.03.004
  2. Transplant Proc. 2018 May;pii: S0041-1345(18)30141-6. [Epub ahead of print]50(4): 1018-1021
    Long-term Follow-up of Living Kidney Donors With Chronic Kidney Disease at 1 Year After Nephrectomy.
    J C Na, J S Park, M-G Yoon, H H Lee, Y E Yoon, K H Huh, Y S Kim, W K Han.
       BACKGROUND: Although renal function recovery of living kidney donors has been reported in a number of studies, many patients show poor recovery, and the long-term prognosis of these patients has not been well studied. In this investigation we explored the long-term prognosis of renal function in patients with chronic kidney disease (CKD) at 1 year after nephrectomy.
    METHODS: Patients who underwent donor nephrectomy during the period from March 2006 to April 2014, with a follow-up creatinine study at 1 year postoperatively and more than 3 years of follow-up, were included in the study. Creatinine and estimated glomerular filtration rate (eGFR, using the Modification of Diet in Renal Disease formula) before and after surgery were studied. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood count, preoperative routine serum chemistry, and urine study results were reviewed.
    RESULTS: Among 841 patients who had donor nephrectomy, 362 were included in the study. There were 111 patients (30.6%) with eGFR <60 mL/min/1.73 m2 at 1 year postsurgery, and the median follow-up period was 62.8 months (interquartile range [IQR] 42.0-86.3 months). The maximum eGFR after 3-year follow-up was studied, and 48 patients (43.2%) never recovered eGFR to >60 mL/min/1.73 m2. Age, history of hypertension, preoperative eGFR, and eGFR at 1 year were predictive factors at univariate analysis. Multivariate analysis of these factors was studied, and age (52.5 [IQR 47-55.7] vs 47 [IQR 7-53] years, odds ratio [OR] 1.1, 95% confidence interval [CI] 1.02-1.15, P = .007), history of hypertension (16.7% vs 1.6%, OR 10.0, 95% CI 1.09-92.49, P = .042), and eGFR at 1 year (53.9 [IQR 50.3-56.0] vs 57.0 [IQR 54.2-58.4] mL/min/1.73 m2, OR 0.8, 95% CI 0.72-0.92, P = .002) remained as significant risk factors.
    CONCLUSION: Of all living donors, 15.7% had CKD after >3 years of follow-up. Close observation is warranted when donors have CKD after 1 year follow-up, as 43.2% fail to recover renal function. Patients who are older, have a history of hypertension, and have low eGFR at 1-year follow-up are especially at risk.
    DOI:  https://doi.org/10.1016/j.transproceed.2018.02.053
  3. Value Health Reg Issues. 2018 May 03. pii: S2212-1099(18)30050-5. [Epub ahead of print]15 155-160
    Cost-Effectiveness Analysis of Renin-Angiotensin Aldosterone System Blockade in Progression of Chronic Kidney Disease.
    Oraluck Pattanaprateep, Atiporn Ingsathit, Mark McEvoy, John Attia, Ammarin Thakkinstian.
       OBJECTIVES: To assess the cost effectiveness of renin-angiotensin aldosterone system (RAAS) blockade in the progression of chronic kidney disease using Thai clinical data in 2014.
    METHODS: A Markov model for cost-effectiveness analysis was applied to estimate from a societal perspective the cost per quality-adjusted life-year (QALY) gained and the incremental cost-effectiveness ratio of RAAS versus non-RAAS used in preventing the progression of end-stage renal disease and death stratified by diabetic and nondiabetic patients. Input parameters related to clinical outcomes were obtained from a cohort study of treatment effectiveness, whereas costs were retrieved from the Ramathibodi Hospital electronic database in 2015 and the Health Intervention and Technology Assessment Program in Thailand. One-way analysis and probabilistic sensitivity analysis were performed to evaluate uncertainty surrounding model parameters.
    RESULTS: From the model, using RAAS improved QALY from 2.41 to 3.16 years and from 2.37 to 3.20 years in diabetic and nondiabetic groups, respectively. The incremental cost-effectiveness ratios for these groups were 78,250 baht (US $2,353.39) and 66,674 baht (US $2,005.22), respectively.
    CONCLUSIONS: Using RAAS in patients with chronic kidney disease improved QALY in both diabetic and nondiabetic patients and proved to be cost-effective.
    Keywords:  chronic kidney disease; cost effectiveness; renin-angiotensin-aldosterone system blockade
    DOI:  https://doi.org/10.1016/j.vhri.2017.12.011
  4. J Clin Pathol. 2018 May 05. pii: jclinpath-2018-205024. [Epub ahead of print]
    Performance of point of care assays for hepatitis B and C viruses in chronic kidney disease patients.
    Jakeline Ribeiro Barbosa, Vanessa Faria Cortes, Moyra Machado Portilho, Juliana Custódio Miguel, Vanessa Alves Marques, Cristianne Sousa Bezerra, Natalia Vasconcelos de Souza, Danielle Malta Lima, Jeová Keny Baima Colares, Lia Laura Lewis-Ximenez, Elisabeth Lampe, Livia Melo Villar.
       AIMS: Point of care testing (POCT) has been used for hepatitis B and C diagnosis in general population, but little is known about the influence of clinical conditions in the accuracy of these assays. This study aims to evaluate the performance of POCTs for detection of hepatitis B virus surface antigen (HBsAg) and antibodies to Hepatitis C Virus (anti-HCV) in Chronic Kidney Disease (CKD) patients.
    METHODS: A total of 286 subjects were included in this study. HBsAg and anti-HCV were detected using commercial EIAs and four POCTs: HBsAg (WAMA Imuno-Rápido HBsAg and VIKIA HBsAg) and anti-HCV (DOLES HCV teste rápido and WAMA Imuno-Rápido anti-HCV) in serum and whole blood.
    RESULTS: Using EIA, HBsAg and anti-HCV prevalence was 4.5% and 16.1% in CKD patients. HBsAg and anti-HCV POCTs had sensitivities from 92.3% to 100% and 84.8% to 89.1% while specificities were 99.3% to 100% and 99.2% to 99.6%, respectively. POCT using serum samples performed well compared with whole blood samples and true positive samples of POCTs had high optical density to cut-off (OD/CO) values compared with EIA.
    CONCLUSIONS: This study demonstrates good performance of HBsAg and anti-HCV POCTs in CKD patients, especially in serum samples indicating low interference of this disease in the performance of these assays. POCTs could be an important tool for HBV and HCV screening in high-risk populations.
    Keywords:  diagnosis; hepatitis; kidney
    DOI:  https://doi.org/10.1136/jclinpath-2018-205024
  5. Transplant Proc. 2018 May;pii: S0041-1345(18)30108-8. [Epub ahead of print]50(4): 1022-1024
    Delayed Recovery of Renal Function After Donor Nephrectomy.
    J C Na, J S Park, M-G Yoon, H H Lee, Y E Yoon, K H Huh, Y S Kim, W K Han.
       BACKGROUND: Many living kidney donors are still at risk of chronic kidney disease (CKD) 1 year after nephrectomy. Although some donors still experience poor renal function, many exhibit delayed recovery of renal function afterwards. We studied the factors related to delayed recovery of renal function in patients with CKD at 1 year after nephrectomy.
    METHODS: Patients who underwent donor nephrectomy from March 2006 to April 2014 with a follow-up creatinine study at 1 month, 6 months, 1 year, and after 3 years of follow-up were included in the study. Age, sex, history of hypertension or diabetes, body mass index, blood pressure, complete blood cell count, preoperative routine serum chemistry, and urine study results were reviewed.
    RESULTS: Among 275 donors, 83 (30.2%) who had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at 1 year of follow-up were included in the study, and the eGFR was observed during a median follow-up of 62.0 months (interquartile range [IQR], 48.9-83.1 months). Those who had improvements in eGFR of >5 mL/min/1.73 m2 were included in the recovery group (n = 48 [57.8%]), and those who did not were included in the nonrecovery group (n = 35 [42.2%]). The preoperative and 1-year follow-up eGFR did not differ significantly between the 2 groups, and the maximum eGFR after 3 years was higher in the recovery group (68.68 mL/min/1.73 m2 [IQR, 61.81-75.64 mL/min/1.73 m2] vs 55.63 mL/min/1.73 m2 [IQR, 51.73-58.29 mL/min/1.73 m2]; P < .001). The recovery group was more likely to have a history of hypertension (4.2% vs 20%; P = .032), a lower body mass index (24.11 kg/m2 [IQR, 22.04-25.20 kg/m2] vs 25.25 kg/m2 [IQR, 23.23-26.44 kg/m2]; P = .01), and a lower preoperative uric acid level (4.7 mg/dL [IQR, 3.8-5.4 mg/dL] vs 5.3 mg/dL [IQR, 4.4-6.2 mg/dL]; P = .031). After multivariate logistic regression analysis, history of hypertension (odds ratio, 0.131; P = .022) and uric acid level (odds ratio, 0.641; P = .036,) remained as significant factors.
    CONCLUSIONS: Although 30.2% of donors had CKD at 1 year after nephrectomy, 57.8% reported improved renal function. Those with a history of hypertension and high preoperative uric acid levels were less likely to have improvements in renal function and required close follow-up.
    DOI:  https://doi.org/10.1016/j.transproceed.2018.01.038
  6. Matrix Biol. 2018 May 03. pii: S0945-053X(18)30053-2. [Epub ahead of print]
    Fibulin-7, a heparin binding matricellular protein, promotes renal tubular calcification in mice.
    Jun Tsunezumi, Hidekazu Sugiura, Lalhaba Oinam, Aktar Ali, Bui Quoc Thang, Aiko Sada, Yoshito Yamashiro, Makoto Kuro-O, Hiromi Yanagisawa.
      Ectopic calcification occurs during development of chronic kidney disease and has a negative impact on long-term prognosis. The precise molecular mechanism and prevention strategies, however, are not established. Fibulin-7 (Fbln7) is a matricellular protein structurally similar to elastogenic short fibulins, shown to bind dental mesenchymal cells and heparin. Here, we report that Fbln7 is highly expressed in renal tubular epithelium in the adult kidney and mediates renal calcification in mice. In vitro analysis revealed that Fbln7 bound heparin at the N-terminal coiled-coil domain. In Fbln7-expressing CHO-K1 cells, exogenous heparin increased the release of Fbln7 into conditioned media in a dose-dependent manner. This heparin-induced Fbln7 release was abrogated in CHO-745 cells lacking heparan sulfate proteoglycan or in CHO-K1 cells expressing the Fbln7 mutant lacking the N-terminal coiled-coil domain, suggesting that Fbln7 was tethered to pericellular matrix via this domain. Interestingly, Fbln7 knockout (Fbln7-/-) mice were protected from renal tubular calcification induced by high phosphate diet. Mechanistically, Fbln7 bound artificial calcium phosphate particles (aCPP) implicated in calcification and renal inflammation. Binding was decreased significantly in Fbln7-/- primary kidney cells relative to wild-type cells. Further, overexpression of Fbln7 increased binding to aCPP. Addition of heparin reduced binding between aCPP and wild-type cells to levels of Fbln7-/- cells. Taken together, our study suggests that Fbln7 is a local mediator of calcium deposition and that releasing Fbln7 from the cell surface by heparin/heparin derivatives or Fbln7 inhibitory antibodies may provide a novel strategy to prevent ectopic calcification in vivo.
    Keywords:  Calcification; Elastogenesis; Fibulin; Kidney; Pericellualr matrix
    DOI:  https://doi.org/10.1016/j.matbio.2018.04.014
  7. Diabetes Metab. 2018 Apr 16. pii: S1262-3636(18)30078-8. [Epub ahead of print]
    Complement activation in patients with diabetic nephropathy.
    X-Q Li, D-Y Chang, M Chen, M-H Zhao.
       AIM: Emerging evidence has indicated a role of the complement system in the pathogenesis of diabetic nephropathy (DN), although the pathways of complement activation and their clinicopathological relevance in DN are as yet unclear. The present study aimed to investigate levels of various complement components in plasma and urine of DN patients, and their correlation with clinicopathological parameters.
    METHODS: A total of 68 biopsy-proven DN patients with plasma samples were recruited, including 50 patients who also had urine samples available. Seven complement components (C1q, MBL, Bb, C4d, C3a, C5a, soluble C5b-9) were measured by enzyme-linked immunosorbent assay (Elisa), and any associations between their levels and clinicopathological parameters were then investigated.
    RESULTS: In DN patients, plasma levels of C1q, MBL, Bb, C4d, C3a, C5a and sC5b-9 were significantly higher than in diabetes patients without renal involvement, as were also urinary levels except for C1q, which showed no significant differences between the two groups. Also, urinary levels of C3a and C5a were significantly correlated with serum creatinine, urinary protein and estimated glomerular filtration rate, whereas urinary sC5b-9 was significantly correlated with the latter two (and not serum creatinine). In addition, urinary levels of MBL, Bb and C4d were significantly correlated with urinary protein, while C3a, C4d and Bb significantly correlated with the classification of glomerular lesions in DN.
    CONCLUSION: In DN patients, the complement system is activated and, of the three possible complement pathways, activation of the lectin and alternative pathways is associated with renal damage.
    Keywords:  Complement; Complement activation pathway; Diabetic nephropathy
    DOI:  https://doi.org/10.1016/j.diabet.2018.04.001
  8. Life Sci. 2018 May 02. pii: S0024-3205(18)30243-1. [Epub ahead of print]
    Dexmedetomidine attenuates renal fibrosis via α2-adrenergic receptor-dependent inhibition of cellular senescence after renal ischemia/reperfusion.
    Qijian Li, Chaojin Chen, Xi Chen, Mingming Han, Juan Li.
       BACKGROUND: Renal ischemia/reperfusion (IR) can induce acute kidney injury (AKI), which often progresses to chronic kidney disease (CKD). Dexmedetomidine (Dex), a highly selective α2 adrenergic receptor (α2-AR) agonist, protects against acute renal IR-induced injury. However, the effects of Dex on the transition of AKI to CKD remain unclear. Therefore, we investigated the mechanisms of Dex on renal fibrosis.
    METHODS: Adult male C57BL/6 mice were pretreated with Dex, a specific α2A-adrenergic receptor (AR) blocker (BRL-44408), or a cell senescence inhibitor (rapamycin) in a surgical bilateral renal IR model. The diagnoses of AKI and chronic renal fibrosis were performed by histopathological staining and western blotting. Histopathological changes, cell senescence, tubular fibrotic markers, and the expression of inflammatory factors were studied.
    RESULTS: Pretreatment with Dex alleviated renal IR-induced AKI and chronic tubulointerstitial fibrosis in later stages. Similar to the effects of rapamycin, pretreatment with Dex also decreased the number of senescent tubular cells and weakened the protein expression of senescence-associated markers such as p53, p21, and p16. Furthermore, the expression of inflammatory markers was also decreased in Dex-treated IR mice; and these protective effects of Dex could be abolished by treatment with the specific α2A-AR blocker, BRL-44408.
    CONCLUSIONS: The administration of a single dose of Dex protects against AKI and CKD. Dex inhibits tubular cell senescence and inflammation as well as improves renal fibrosis to moderate the AKI-to-CKD transition. The renal protective potential of Dex may provide a novel treatment strategy for high-risk renal injury patients.
    Keywords:  Dexmedetomidine; Fibrosis; Inflammation; Renal ischemia reperfusion; Senescence
    DOI:  https://doi.org/10.1016/j.lfs.2018.05.003
  9. Diabetes Res Clin Pract. 2018 May 03. pii: S0168-8227(17)31528-0. [Epub ahead of print]141 62-68
    Clinical predictive biomarkers for normoalbuminuric diabetic kidney disease.
    Tomohito Gohda, Yuji Nishizaki, Maki Murakoshi, Shuko Nojiri, Naotake Yanagisawa, Terumi Shibata, Mami Yamashita, Kanako Tanaka, Yoshinori Yamashita, Yusuke Suzuki, Nozomu Kamei.
       AIMS: A portion of patients with diabetes mellitus follow the progression of a non-albuminuria-based pathway; i.e., normoalbuminuric diabetic kidney disease (NA-DKD). However, the risk factors which determine NA-DKD are not yet fully understood. This cross-sectional study was therefore aimed to investigate the association between various biomarker levels and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus and normoalbuminuria (T2D-NA).
    METHODS: We measured cardiovascular disease (CVD) [serum osteoprotegerin (OPG), plasma brain natriuretic peptide (BNP), cardio-ankle vascular index (CAVI)], tubular damage [urinary L-type fatty acid binding protein (L-FABP)], and inflammatory [serum tumornecrosis factor (TNF) α and its receptors (TNFRs)] biomarkers in 314 patients with T2D-NA.
    RESULTS: The biomarkers of CVD and inflammation showed a significant negative correlation with eGFR. In a logistic multivariate model, none of the biomarkers, except TNFα and TNFRs, were associated with reduced renal function (eGFR < 60 mL/min/1.73 m2) after adjustment for possible biological and clinical covariates. However, the association observed in TNFα was lost after adjusting for TNFR and other covariates.
    CONCLUSIONS: In patients with T2D-NA, elevated levels of circulating TNFRs, but not of TNFα, were strongly associated with reduced renal function, independently of all relevant covariates.
    Keywords:  Biomarker; DKD; Normoalbuminuria; TNFR; TNFα
    DOI:  https://doi.org/10.1016/j.diabres.2018.04.026
  10. Transplant Proc. 2018 May;pii: S0041-1345(18)30126-X. [Epub ahead of print]50(4): 1009-1012
    Clinical Outcomes of Kidney Transplantation in Patients With Biopsy-Proven Glomerulonephritis.
    H Park, W Y Park, S S Kang, S M Yeo, S Han, S B Park, K Jin.
       BACKGROUND: The clinical outcomes after kidney transplantation (KT) according to the types of glomerulonephritis (GN) as the cause of end-stage renal disease (ESRD) are various, but there are not many studies on this.
    METHODS: Among 1,253 patients who had KT between November 1982 and January 2017, 183 recipients with biopsy-proven GN as the primary cause of ESRD were enrolled. We analyzed the incidence of recurrent GN and the factors associated with recurrence and graft and patient survivals.
    RESULTS: The types of GN were 95 IgA nephropathy, 47 focal segmental glomerulosclerosis, 14 membranous proliferative GN, 9 membranous GN, 8 lupus nephritis, 6 rapid progressive GN, and 4 Alport syndrome. The mean follow-up duration was 103 ± 81.7 months. Recurrence was reported in 36 patients, of which 20 grafts failed due to recurrence. The age of patients with GN recurrence was significantly younger than that of patients without GN recurrence (P = .030). The graft failure rate of KT recipients with recurrent GN was significantly higher than that of the recipients without recurrent GN (55.6% vs 18.4%, P < .001). In multivariate analysis, recurrence of primary GN, the number of HLA mismatches at AB, delayed graft function, and acute rejection were independent risk factors for graft failure.
    CONCLUSION: Recurrent GN remains a significant cause of graft loss in KT recipients. Surveillance of GN recurrence in the KT recipients with biopsy-proven GN can reduce allograft dysfunction.
    DOI:  https://doi.org/10.1016/j.transproceed.2018.02.039
  11. Kidney Int. 2018 May 02. pii: S0085-2538(18)30195-9. [Epub ahead of print]
    C3 glomerulopathy associated with monoclonal Ig is a distinct subtype.
    Aishwarya Ravindran, Fernando C Fervenza, Richard J H Smith, Sanjeev Sethi.
      Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45.8% patients; pathogenic variants in complement protein genes were rare. Hematologic evaluation revealed monoclonal gammopathy of renal significance in 26 patients, multiple myeloma in five, smoldering multiple myeloma in two, and chronic lymphocytic leukemia, lymphoma, or type I cryoglobulin each in one patient. After a median follow-up of 43.6 months, the median serum creatinine and proteinuria were 1.4 mg/dL and 0.8g/24 hours. Nine patients developed ESRD. Sixteen patients received MIg-targeted treatment, 17 patients received non-targeted treatment while three patients were managed conservatively. Of the 16 patients receiving MIg-targeted treatment, ten achieved complete/very good/partial hematologic response. Of these, seven achieved a complete/partial/stable renal response. Five patients receiving targeted treatment did not achieve hematologic response, none had a renal response. Patients receiving targeted treatment were more likely to have multiple myeloma/smoldering multiple myeloma. Patients receiving non-targeted treatment were more likely to have monoclonal gammopathy of renal significance. Thus, C3G with MIg is seen in older patients, C3 nephritic factor is the most common autoantibody detected, and MIg-targeted treatment may result in remission and stabilization of kidney function in a subset of these patients.
    Keywords:  C3 glomerulonephritis; C3 glomerulopathy; alternative pathway of complement; dense deposit disease; monoclonal Ig
    DOI:  https://doi.org/10.1016/j.kint.2018.01.037
  12. Nefrologia. 2018 May - Jun;38(3):pii: S0211-6995(17)30211-4. [Epub ahead of print]38(3): 279-285
    Bone and mineral metabolism at 55 haemodialysis centres in Lima.
    Pedro Méndez-Chacón, Nicolás Riccobelli, María P Dionisi, Emilio Sánchez-Álvarez, Fernando Bardales-Viguria, Carla Méndez-Chacón Rodríguez, Jorge B Cannata-Andía, José L Fernández-Martín.
       BACKGROUND: Mineral and bone metabolism disorders are common complications in haemodialysis patients that present significant geographical variability.
    OBJECTIVES: The objective of this study was to assess these disorders for the first time in haemodialysis patients from Peru.
    METHODS: The study included 1551 haemodialysis patients from 55 centres affiliated with the Social Health System of Peru in the city of Lima. Demographic data, comorbidities, treatments and biochemical parameters were collected from each patient. Serum calcium, phosphorus and PTH levels were categorised according to the recommended ranges in the KDOQI and KDIGO guidelines.
    RESULTS: The mean age of the patients was 59.5±15.6 years, with a mean time on haemodialysis of 58.0±54.2 months. All patients were dialysed with a calcium concentration in the dialysis fluid of 3.5 mEq/l and 68.9% of patients were prescribed phosphate-binding agents (98.4% of them calcium carbonate). A high percentage of patients showed serum calcium above, and serum phosphorus below, the recommended ranges in the KDOQI guidelines (32.8% and 37.3%, respectively). More than half of the patients had serum PTH values below the recommended ranges of both the KDOQI and KDIGO guidelines (56.4% and 51.6%, respectively).
    CONCLUSIONS: Patients included in this study were younger than those from other studies and showed both hypophosphataemia and suppressed PTH, probably due to an excessive calcium overload through dialysis fluid and the use of calcium-containing phosphate binding agents.
    Keywords:  Calcio; Calcium; Chronic kidney disease; Enfermedad renal crónica; Fósforo; Haemodialysis; Hemodiálisis; Hormona paratiroidea; Parathyroid Hormone; Phosphorus
    DOI:  https://doi.org/10.1016/j.nefro.2017.09.011
  13. Transplant Proc. 2018 May;pii: S0041-1345(18)30094-0. [Epub ahead of print]50(4): 1001-1004
    Is the Clinical Outcome Good or Bad in Patients Hospitalized Within 1 Year After Kidney Transplantation?
    W Y Park, S S Kang, K Jin, S B Park, S Han.
       BACKGROUND: Although the hospitalization rate at early period of kidney transplantation (KT) is still high, the association between the hospitalization within 1 year after KT and graft survival is unclear. We investigated the incidence and causes of hospitalization and clinical outcome of the patients hospitalized within 1 year after KT.
    METHODS: We retrospectively analyzed 174 KT recipients (KTRs) hospitalized within 1 year after KT between 2013 and 2015.
    RESULTS: Among them, 84 (48%) KTRs were admitted within 1 year after KT, and the number of hospitalizations was 116. The mean time from KT to first hospitalization was 4.2 months. Seventy-eight percent of the patients were hospitalized for medical causes and 22% for surgical causes. The most common cause was cytomegalovirus infection (CMV) (23.3%), followed by acute rejection (11.2%) and urinary tract infection (10.3%). Recipients and donors in the hospitalized group were significantly older than the nonhospitalized group. The proportions of deceased donor KT, acute rejection, more than 50% panel-reactive antibody, and positive donor-specific antibody were significantly higher in the hospitalized group than in the nonhospitalized group. Graft and patient survivals were lower in the hospitalized group than in the nonhospitalized group. Deceased donor KT and acute rejection were independent risk factors for hospitalization.
    CONCLUSION: The incidence of KTRs hospitalized within 1 year after KT was high. Most causes of hospitalization were CMV infection, acute rejection, and urinary tract infection. Therefore, the immunosuppression status of these patients should be closely monitored to reduce the hospitalization rate.
    DOI:  https://doi.org/10.1016/j.transproceed.2018.01.027
  14. Kidney Int. 2018 May 04. pii: S0085-2538(18)30181-9. [Epub ahead of print]
    Kidney-targeted inhibition of protein kinase C-α ameliorates nephrotoxic nephritis with restoration of mitochondrial dysfunction.
    Nino Kvirkvelia, Malgorzata McMenamin, Marie Warren, Ravirajsinh N Jadeja, Sai Karthik Kodeboyina, Ashok Sharma, Wenbo Zhi, Paul M O'Connor, Raghavan Raju, Rudolf Lucas, Michael P Madaio.
      To investigate the role of protein kinase C-α (PKC-α) in glomerulonephritis, the capacity of PKC-α inhibition to reverse the course of established nephrotoxic nephritis (NTN) was evaluated. Nephritis was induced by a single injection of nephrotoxic serum and after its onset, a PKC-α inhibitor was administered either systemically or by targeted glomerular delivery. By day seven, all mice with NTN had severe nephritis, whereas mice that received PKC-α inhibitors in either form had minimal evidence of disease. To further understand the underlying mechanism, label-free shotgun proteomic analysis of the kidney cortexes were performed, using quantitative mass spectrometry. Ingenuity pathway analysis revealed 157 differentially expressed proteins and mitochondrial dysfunction as the most modulated pathway. Functional protein groups most affected by NTN were mitochondrial proteins associated with respiratory processes. These proteins were down-regulated in the mice with NTN, while their expression was restored with PKC-α inhibition. This suggests a role for proteins that regulate oxidative phosphorylation in recovery. In cultured glomerular endothelial cells, nephrotoxic serum caused a decrease in mitochondrial respiration and membrane potential, mitochondrial morphologic changes and an increase in glycolytic lactic acid production; all normalized by PKC-α inhibition. Thus, PKC-α has a critical role in NTN progression, and the results implicate mitochondrial processes through restoring oxidative phosphorylation, as an essential mechanism underlying recovery. Importantly, our study provides additional support for targeted therapy to glomeruli to reverse the course of progressive disease.
    Keywords:  PKC-α inhibition; glomerular endothelial cells; mitochondrial dysfunction; nephritis; proteomics; targeted delivery
    DOI:  https://doi.org/10.1016/j.kint.2018.01.032
  15. Nat Rev Nephrol. 2018 May 05.
    Haemodialysis membranes.
    Claudio Ronco, William R Clark.
      Haemodialysis is an extracorporeal process in which the blood is cleansed via removal of uraemic retention products by a semipermeable membrane. Traditionally, dialysis membranes have been broadly classified on the basis of their composition (cellulosic or noncellulosic) and water permeability (low flux or high flux). However, advances in materials technology and polymer chemistry have led to the development of membranes with specific characteristics and refined properties that mandate a reconsideration of traditional membrane classification systems. For adequate characterization of these newer types of membranes, additional parameters are now relevant, including new permeability indices, the hydrophilic or hydrophobic nature of membranes, adsorption capacity and electrical potential. In this Review, we provide clinicians with an updated analysis of dialysis membranes and dialysers. We discuss the basic mechanisms that underlie solute and water removal in dialysis (that is, diffusion, convection, adsorption and ultrafiltration) in the context of treatments that use highly permeable membranes. Specifically, we highlight online haemodiafiltration and new therapies (for example, expanded haemodialysis) that utilize membranes designed to produce a high degree of internal filtration. Finally, we discuss the considerations that govern the clinically acceptable balance between large-solute clearance and albumin loss for extracorporeal therapies.
    DOI:  https://doi.org/10.1038/s41581-018-0002-x
  16. Clin Exp Nephrol. 2018 May 05.
    On the nature of toenail opacities in renal insufficiency.
    Sigurd Delanghe, Marijn Speeckaert, Sander De Bruyne, Joris Delanghe.
      
    DOI:  https://doi.org/10.1007/s10157-018-1576-0
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