Photopheresis Abates the Anti-HLA Antibody Titer and Renal Failure Progression in Chronic Antibody-Mediated Rejection

Objective: Chronic renal antibody-mediated rejection (ABMR) is a common cause of allograft failure, but an effective therapy is not available. Extracorporeal photopheresis (ECP) has been proven successful in chronic lung and heart rejection, and graft versus host disease. The aim of this study was to evaluate the effectiveness of ECP in chronic ABMR patients. Patients and Methods: We investigated ECP treatment in 14 patients with biopsy-proven chronic ABMR and stage 2–3 chronic renal failure. The primary aim was to e valuate the eGFR lowering after 1 year of ECP therapy. The ECP responders (R) showed eGFR reduction greater than 20% vs the basal levels. We also evaluated the effectiveness of ECP on proteinuria, anti-HLA antibodies (HLAab), interleukin 6 (IL-6) serum levels, and CD3, CD4, CD8, CD19, NK, Treg and T helper 17 (Th17) circulating cells. Results: Three patients dropped out of the study. The R patients were eight (72.7%) out of the 11 remaining patients. Because ECP was not associated with any adverse reaction, the R patients continued such treatment for up to 3 years, showing a persisting eGFR stabilization. Twenty four hour proteinuria did not increase in the R patients over the follow-up when compared to the non-responder patients (NR). In the R patients, the HLAab levels were reduced and completely cleared in six out of eight patients when compared with the NR patients. The NR HLAab levels also increased after the discontinuation of the ECP. The ECP in the R patients showed a decrease in CD3, CD4, CD8, CD19, and NK circulating cells. The ECP treatment in the R patients also induced Tregs and Th17 cell increases, and a decrease of the IL-6 serum levels. Conclusions: ECP abates the HLAab titer and renal failure progression in patients with chronic renal ABMR, modulating the immune cellular and humoral responses.

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Response to JAK 1/2 Inhibition in Patients with Corticosteroid-Refractory Acute Graft-Versus-Host Disease

Blood ◽

10.1182/blood.v124.21.3934.3934 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3934-3934 ◽

Cited By ~ 2

Author(s):

Silvia Spoerl ◽

Kristina Maas-Bauer ◽

Mareike Verbeek ◽

Petya Apostolova ◽

Anna Lena Illert ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Chronic Gvhd ◽

Complete Response ◽

Serum Levels ◽

Salvage Treatment ◽

Hematopoietic Stem ◽

Host Disease ◽

Graft Versus Host ◽

Number Of Patients

Abstract Acute corticosteroid-refractory graft-versus-host-disease (GvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reported mortality rates of 40-60%. Our previous study (Spoerl S et al. Blood 2014) had shown the induction of tolerogenic regulatory T cells after ruxolitinib treatment in the mouse and clinical responses in six patients with corticosteroid-refractory GvHD. Here we report the outcome of 14 patients with GvHD refractory to steroids and at least two other lines of treatment who received ruxolitinib as a salvage treatment. Ten patients were classified as acute and four as chronic GvHD involving the skin, intestinal tract and liver as detailed in Table 1. Patients were treated with ruxolitinib at a starting dose of 5 mg orally twice daily with a dose increase to 10 mg orally twice daily. Clinical and histopathological grading of skin, intestinal and liver GvHD was performed according to established criteria. Of 14 patients, 13 responded with respect to clinical GvHD symptoms and serum levels of pro-inflammatory cytokines. Three patients with histologically proven acute skin or intestinal GvHD grade I, achieved a complete response. One non-responder discontinued ruxolitinib after one week because of lack of efficacy. In all other patients corticosteroids could be reduced after a median treatment of 1.5 weeks. Serum levels of IL-6 and soluble IL-2R were measured prior and after the start of ruxolitinib and declined in the majority of the analyzed patients (n=11). CMV reactivation was observed in four out of 14 patients and responded well to antiviral therapy. Two out of 14 patients developed cytopenia during ruxolitinib treatment that was mild and did not require dose reduction or transfusion. Our results indicate that treatment of corticosteroid-refractory GvHD with ruxolitinib is safe and well tolerated. Despite the low number of patients treated so far, our results demonstrate that ruxolitinib reduces the severity of corticosteroid-refractory GvHD and support further development of therapeutic JAK1/2 inhibition as a salvage treatment in GvHD. Table 1: GvHD and response to ruxolitinib Pt. no. 1 GvHD: organ/grade 2 Reduction of cortico-steroids after ruxolitinib Clinical response (PR / CR) 3 Time to response (weeks) Duration of response 4 / Current follow up (weeks) 5 01 Intestines / IV (acute) Yes CR 1 42 / 43 02 Skin / III (acute) Yes PR 1.5 46.5 / 48 03 Skin / IV liver / III (acute) Yes CR 1 57 / 58 04 Skin / III intestines / IV (acute) Yes PR 1.5 24.5 / 26 05 Skin / III (chronic) Yes PR 1 64 / 65 06 intestine/III-IV (acute) Yes PR 1 15 / 16 07 Skin/ III (chronic) Yes Response 1 46 / 47 08 Skin/ III (acute) Yes Response 1 2 / 3 09 Skin/ II intestine/II (chronic) Yes No response stopped after 1 week N/A N/A 10 Skin/ III liver/III (acute) Yes PR 1 1 / 2 11 intestines IV (acute) Yes PR 2 6 / 8 12 Skin/III (chronic) Yes Response 1 8 / 9 13 intestines/IV Skin/ II (late onset acute) Yes CR 1 17 / 18 14 intestines/IV Skin/ II (acute) Yes PR 1,5 3 / 4 1Pt.: patient, no: individual patient number, 2Acute and chronic GvHD were defined according to NIH criteria, 3PR: partial response, CR: complete response; 4Until last follow up, none of the patients experienced a relapse of GvHD. 5Follow up was calculated from the time of initiation of ruxolitinib treatment. In patient 01, ruxolitinib was discontinued at week 16 because of complete resolution of all GvHD signs. The patient did not develop any signs of GvHD after discontinuation of ruxolitinib until last follow up. Disclosures Off Label Use: Ruxolitinib in GvHD.

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HLA and Kir Mismatch Transplant Affect Cytopenia Beyond Day 28 after Thalassemia Transplant: A Primary Manifestation of Chronic Graft Versus Host Disease

Blood ◽

10.1182/blood.v124.21.5929.5929 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5929-5929

Author(s):

Xiaohui Zhou ◽

Chunfu Li ◽

Jianyun Liao ◽

Xiangjun Liu

Keyword(s):

Conflicts Of Interest ◽

Hla Class I ◽

Thalassemia Major ◽

Class I ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Graft Versus Host ◽

Hla Antibody ◽

Cmv Status

Abstract Background Cytopenia beyond day 28 post-transplant (CB-28PT) following hematopoietic stem cell transplantation (HSCT) with β-thalassemia major (TM) rarely was reported. The exact mechanism for the development of CB-28PT is not well known. Aim To find out causes of CB-28PT cytopenia. Method We retrospectively analyzed data (HLA mismatch status, HLA antibody status of patients, KIR gene mismatch status, KIR-ligand matching status, donor/patient CMV status, donor/patient age and sex) of 93 TM patients underwent HLA 8/8 fully matched or 7/8 matched unrelated donor HSCT. All the patients used sole NF-08-TM protocol with median follow-up time of 19 (r: 2-44) months. Results Results show a significant association between DRB1 mismatch and CB-28PT (P = 0.012). In addition, presence of Class I HLA antibody in the patient’s sera seems increase the chance of CB-28PT. Finally, the matching between inhibitory KIR2DL1 and their corresponding ligand HLA-C2 has a protective effect for CB-28PT. Conclusion We propose that CB-28PT may be a primary manifestation of cGVHD in pediatric TM patients undergoing HSCT positive influenced by HLA DRB1 mismatch, HLA class I antibody and negatively affected by KIR-ligand match. Disclosures No relevant conflicts of interest to declare.

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Heart transplantation and antibody-mediated rejection: role of myocardial strain as an early marker of cardiac dysfunction in patients with anti-HLA antibody

European Heart Journal ◽

10.1093/eurheartj/ehab724.0961 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

C Sciaccaluga ◽

B.M Natali ◽

G.E Mandoli ◽

N Sisti ◽

F.M Righini ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Myocardial Strain ◽

Strain Analysis ◽

Left Ventricular ◽

Hla Antibodies ◽

Antibody Mediated Rejection ◽

Right Ventricular Strain ◽

Hla Antibody

Abstract Background Antibody-mediated rejection of the transplanted heart is still currently diagnosed by endomyocardial biopsy whereas clinical elements, anti-Human Leukocite Antigens (HLA) antibody and graft dysfunction represents supplementary components. Purpose The aim of the study was to identify though a non-invasive imaging technique, such as advanced transthoracic echocardiography, early signs of altered cardiac function in patients with anti-HLA antibodies and no histological signs of antibody-mediated rejection. Methods The study population included 117 heart transplanted patients, in whom both acute and chronic rejection was excluded. They were divided into two groups “HLA+`' (45 patients) and “HLA−” (72 patients), based on the presence and the absence of circulating anti-HLA antibodies, respectively. The echocardiographic exam was performed within one week from the biopsy, including Speckle Tracking analysis. Results Deceleration Time of E wave was the strongest traditional echocardiographic parameter which correlated with circulating anti-HLA antibodies (165±39,5 vs 196,5±25; p<0.001). Regarding strain analysis, both left ventricular global longitudinal strain (−16,1±3,4 vs −19,8±2,0; p<0.001) and right ventricular strain (−17,2±0,7 vs −20,6±0,5; p=0.0002) differed significantly between the two subgroups (Figure 1). On the other hand, neither peak atrial longitudinal strain nor peak atrial contraction strain showed a significant correlation with anti-HLA antibodies. Conclusion The presence of circulating anti-HLA antibodies seems to be correlated with a mild cardiac dysfunction, even in the absence of antibody-mediated rejection. This subtle dysfunction is not completely detectable by standard echocardiographic parameters, whereas strain analysis has showed promising results since it revealed more clearly an impaired function of both ventricles in heart transplanted HLA+ patients, with potentially important clinical repercussion. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

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Serum Concentrations of Laminin-P1 in Thrombotic Microangiopathy

Journal of the American Society of Nephrology ◽

10.1681/asn.v113434 ◽

2000 ◽

Vol 11 (3) ◽

pp. 434-443

Author(s):

ALFONS SEGARRA ◽

RAFAEL SIMÓ ◽

LLUIS MASMIQUEL ◽

ROSA M. SEGURA ◽

VICENS FONOLLOSA ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Basement Membrane ◽

Renal Involvement ◽

Serum Levels ◽

Renal Outcome ◽

Serum Concentrations ◽

Healthy Control ◽

Regular Hemodialysis

Abstract. Laminin is the main noncollagenous constituent of the basement membrane, and its serum levels could reflect the metabolic changes that occur in the basement membrane. Severe endothelial injury with thickening of basement membrane is a characteristic feature of thrombotic microangiopathy (TMA). With this background, the aim of the study was to investigate in a prospective way (1) the relationship among serum Lam-P1, the extent of renal histopathologic lesions, and the biochemical parameters commonly used as markers of TMA activity, and (2) the usefulness of serum Lam-P1 concentrations as a renal outcome prognostic index. To this end, 18 consecutive patients with active biopsy-proven TMA with renal involvement were studied. One hundred and twenty-one healthy control subjects, 20 patients with systemic scleroderma without renal involvement, and 35 patients with systemic lupus erythematosus (20 without nephropathy and 15 with diffuse proliferative type 4 lupus nephritis) were used as control groups. In addition, to analyze the influence of either renal failure or hemodialysis therapy on serum Lam-P1 levels, 91 patients on regular hemodialysis therapy and 81 patients with predialysis chronic renal failure of different etiologies were included in the study. Serum Lam-P1 was determined by RIA at admission, on days 10 and 30 of follow-up in all patients, and after 6 and 12 mo of follow-up in all surviving patients. Serum lactate dehydrogenase, haptoglobin, platelet count, hemoglobin, and serum creatinine were determined as markers of endothelial dysfunction and hemolysis. At admission, serum levels of Lam-P1 were significantly higher in patients with TMA than in healthy control subjects (3.39 ± 0.56 U/ml versus 1.40 ± 0.18 U/ml; P < 0.0001). In addition, patients with TMA had significantly higher serum Lam-P1 levels than the other groups included in the study. At the first control, Lam-P1 correlated with lactate dehydrogenase (P = 0.006) and hemoglobin (P = 0.002). During follow-up, platelet count and hemolysis indicators normalized in all patients, while serum Lam-P1 decreased only in patients with renal function recovery. In multivariate analysis, serum creatinine and Lam-P1 at day 10 were the only independent predictors of renal outcome (r2 = 0.94; P < 0.0001) and also correlated with indices of histopathologic damage (P < 0.001). Serum Lam-P1 normalized in all patients with chronic renal failure in the samples obtained at 6 and 12 mo of regular hemodialysis after solving active TMA, thus suggesting that histopathologic lesions, but not renal function itself, would be mainly responsible for the high Lam-P1 serum concentrations detected in TMA. In conclusion, serum Lam-P1 concentrations are increased in patients with active TMA. Furthermore, patients with poor renal outcome show a prolonged increase of serum Lam-P1 that is related to the extent of renal histologic lesions. Unlike the biochemical markers of hemolysis commonly used to assess TMA activity, the sequential determination of serum Lam-P1 provides valuable information about long-term renal prognosis in patients with TMA.

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Association of non-HLA antibodies against endothelial targets and donor-specific HLA antibodies with antibody-mediated rejection and graft function in pediatric kidney transplant recipients

Pediatric Nephrology ◽

10.1007/s00467-021-04969-1 ◽

2021 ◽

Author(s):

Alexander Fichtner ◽

Caner Süsal ◽

Britta Höcker ◽

Susanne Rieger ◽

Rüdiger Waldherr ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hla Antibodies ◽

Antibody Mediated Rejection ◽

Peritubular Capillaries ◽

Increased Risk ◽

Antibody Positivity ◽

Hla Antibody

Abstract Background Non-HLA antibodies against endothelial targets have been implicated in the pathogenesis of antibody-mediated rejection (ABMR), but data in pediatric patients are scarce. Methods We retrospectively analyzed a carefully phenotyped single-center (University Children’s Hospital Heidelberg, Germany) cohort of 62 pediatric kidney transplant recipients (mean age at transplantation, 8.6 ± 5.0 years) at increased risk of graft function deterioration. Patients had received their transplant between January 1, 1999, and January 31, 2010. We examined at time of late index biopsies (more than 1-year post-transplant, occurring after January 2004) the association of antibodies against the angiotensin II type 1 receptor (AT1R), the endothelin type A receptor (ETAR), the MHC class I chain-like gene A (MICA), and vimentin in conjunction with overall and complement-binding donor-specific HLA antibodies (HLA-DSA) with graft histology and function. Results We observed a high prevalence (62.9%) of non-HLA antibody positivity. Seventy-two percent of HLA-DSA positive patients showed additional positivity for at least one non-HLA antibody. Antibodies against AT1R, ETAR, and MICA were associated with the histological phenotype of ABMR. The cumulative load of HLA-DSA and non-HLA antibodies in circulation was related to the degree of microinflammation in peritubular capillaries. Non-HLA antibody positivity was an independent non-invasive risk factor for graft function deterioration (adjusted hazard ratio 6.38, 95% CI, 2.11–19.3). Conclusions Our data indicate that the combined detection of antibodies to HLA and non-HLA targets may allow a more comprehensive assessment of the patients’ immune responses against the kidney allograft and facilitates immunological risk stratification.

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Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-2018-0244 ◽

2020 ◽

Vol 42 (2) ◽

pp. 201-210

Author(s):

Marcos Vinicius de Sousa ◽

Ricardo de Lima Zollner ◽

Marilda Mazzali

Keyword(s):

Renal Function ◽

Ischemia Reperfusion Injury ◽

Interstitial Fibrosis ◽

Ischemia Reperfusion ◽

Graft Function ◽

Kidney Graft ◽

Kidney Transplant Recipients ◽

Hla Antibodies ◽

Antibody Mediated Rejection

Abstract Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

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Abstract 13048: Do Anti-HLA Antibodies Pre-heart Transplant Truly Impact Post-transplant Outcomes?

Circulation ◽

10.1161/circ.142.suppl_3.13048 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Timothy Ho ◽

Jignesh K Patel ◽

Keith Nishihara ◽

Michelle M Kittleson ◽

David H Chang ◽

...

Keyword(s):

Heart Transplant ◽

Term Survival ◽

Hla Antibodies ◽

Major Barrier ◽

Antibody Mediated Rejection ◽

Lv Dysfunction ◽

Significant Difference ◽

Antibody Levels ◽

Hla Antibody

Introduction: Antibody-mediated rejection (AMR) continues to be a major barrier to favorable long-term outcomes and long-term survival. Sensitized pre-heart transplant (HTx) patients, those with anti-HLA antibodies, have previously demonstrated increased post-HTx rejection risk as well as increased mortality. In the current era, there is contention as to whether pre-HTx antibodies result in poor outcome after HTx. Methods: Between 2010 and 2015, 580 HTx patients were assessed for pre-HTx panel reactive antibodies (PRA). PRA levels were measured by the Luminex Single Antigen assay. Patients were divided into 5 groups of PRA levels including 0%, n=423 (Control); PRA 1-10%, n= 21; PRA 11-25%, n=24; PRA 26-50%, n=49; PRA 51-75%, n=32; and PRA >75%, n=35. Endpoints included 5-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE), freedom from donor specific antibody (DSA) development, and freedom from LV dysfunction (LV ejection fraction ≤40%) and 1-year freedom from rejection (any treated rejection (ATR), acute cellular rejection (ACR), AMR). Results: All groups with PRA >10% had significantly lower 1-year freedom from AMR and 5-year freedom from DSA compared to the control, worsening with higher the PRA group. There was no significant difference in 5-year survival, 5-year freedom from CAV, NF-MACE, or LV dysfunction and 1-year freedom from ATR or ACR. Conclusions: Patients with increased anti-HLA antibody levels pre-HTx do not appear to have lower 5-year survival compared to patients without anti-HLA antibody levels. However, the development of 1-year AMR and 5-year DSA increased progressively with higher the PRA group. Further studies and longer follow-up are needed to better understand the effects of elevated pre-HTx PRA, immune therapies (desensitization) and post-HTx outcomes.

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P890 Heart transplantation and antibody-mediated rejection: role of the strain as an early marker of cardiac dysfunction in patients with anti-HLA antibody

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.530 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

B M Natali ◽

F M Righini ◽

M Cameli ◽

C Sciaccaluga ◽

S Bernazzali ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Endomyocardial Biopsy ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Strain Analysis ◽

Invasive Technique ◽

Hla Antibodies ◽

Antibody Mediated Rejection ◽

Echocardiographic Parameters ◽

Hla Antibody

Abstract Background Antibody-mediated rejection of the transplated heart is essentially diagnosed through endomyocardial biopsy whereas clinical elements, anti- Human Leukocite Antigens (HLA) antibody and graft dysfunction are supplementary components. Over the years, several studies have tried to define early diagnostic markers, but to date a univocal consensus has not been achieved. Purpose The aim of the study was to identify though a non-invasive technique, such as transthoracic echocardiography, early signs of impaired cardiac function in heart transplanted patients, in presence of anti-HLA antibodies but without any histological sign of antibody-mediated rejection, assessed through endomyocardial biopsy. Methods In the study 29 heart transplanted patients were enrolled, and they were divided into two groups ‘HLA+’ (15 patients) and ‘HLA-’ (14 patients), based on the presence and the absence of circulating anti-HLA antibodies, respectively. None of the patients had evidence of either coronary allograft vasculopathy or antibody-mediated rejection, attested by endomyocardial biopsy. Each patient underwent through echocardiographic exam, within one month from the biopsy, analysing standard parameters of both systolic and diastolic function, together with strain analysis of right and left ventricle (RV and LV) and left atrium (LA). Results Clinical and demographic characteristics did not different significantly between the two groups, and neither did standard echocardiographic parameters. The only significant parameter that show a statistically significant different was Deceleration Time of E wave (DecT E), which resulted to be lower in the ‘HLA+’ group. Regarding strain analysis, peak atrial longitudinal strain was significantly different between HLA+ and HLA- patients (10,9 ± 5,6 vs 14,9 ± 4,5; p < 0.005), whereas peak atrial contraction strain did not. The study attested a strong difference of both LV global longitudinal strain (- 20,2 ± 5,9 vs - 23,2 ± 3,3; p < 0.005) and RV strain between the two analysed subsets (-16,9 ± 3,4 vs -19,3 ± 3,1 p < 0.005). The figure shows the most significant correlations found in the study, respectively RV strain (on the left), LV strain (in the middle) and DecT E (on the right), the figures on top are representative of HLA- patients, whereas the ones at the bottom are representative of HLA+ patients. Conclusion The presence of circulating anti-HLA antibodies seems to be correlated with a mild cardiac dysfunction, even in the absence of antibody-mediated rejection. This subtle dysfunction is not completely detectable by standard echocardiographic parameters, whereas strain analysis has showed promising results since it revealed more clearly an impaired function of both ventricles in heart transplanted HLA+ patients, with potentially important clinical repercussion. Abstract P890 Figure.

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Renal Effects of Diazoxide and Frusemide and Interrelattonships

Scottish Medical Journal ◽

10.1177/00369330740190s105 ◽

1974 ◽

Vol 19 (1_suppl) ◽

pp. 17-24

Author(s):

J. E. F. Pohl ◽

J. D. Swales ◽

H. Thurston

Keyword(s):

Renal Failure ◽

Ethacrynic Acid ◽

Serum Levels ◽

Normal Range ◽

Severe Renal Failure ◽

Hypertensive Patients ◽

Daily Dose ◽

The Mean

The successful long-term control of diazoxide-induced Na retention in 52 hypertensive patients (mean creatinine clearance (Ccr) 38 ± 30.6 ml/min, range 1–123 ml/min) by the use of potent diuretics is reported. The mean duration of follow-up was 26.2± 14.4 months with a range of 3–52 months. The mean daily dose of frusemide was 344 mg (range 40–1000 mg). The mean daily dose of ethacrynic acid was 318 mg (range 100–800 mg). Rashes necessitating change of therapy were attributed to frusemide in seven patients. Diuretic dosage, corrected for patient Na intake, was independent of diazoxide serum levels (S.L.) below 100 mg/litre but was inversely correlated with CCI (rdiuretic, NaCCI(S.L. constant)= −0.33 2P<0.05). Concordant estimates of patient Na intake were obtained and the estimated mean daily Na intake of 121.2 ±62.1 mEq falls within the normal range. The eight patients with estimated mean Na intakes < 50 mEq/day (mean: 35 mEq/day) had a mean Ccr of 11.04 ± 5.98 ml/min whilst the 31 patients with estimated mean Na intakes > 100 mEqjday (mean: 158.9 mEqjday) had a mean Ccr of 48.92 ± 5.05 ml/min. This discrepancy was interpreted as due to a limitation in the ability to correct diazoxide-induced Na retention in patients with severe renal failure. In practice such patients are kept in balance by the use of more than one diuretic combined with a restricted Na intake.

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Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000190 ◽

2014 ◽

Vol 84 (1-2) ◽

pp. 27-34 ◽

Cited By ~ 7

Author(s):

Nasser M. Al-Daghri ◽

Khalid M. Alkharfy ◽

Nasiruddin Khan ◽

Hanan A. Alfawaz ◽

Abdulrahman S. Al-Ajlan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Vitamin D ◽

Type 2 Diabetes Mellitus ◽

Serum Levels ◽

Vitamin D Supplementation ◽

Serum Selenium ◽

Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

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