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1.
Transpl Int ; 37: 11614, 2024.
Article in English | MEDLINE | ID: mdl-38468637

ABSTRACT

Kidney transplant recipients (KTRs) are at increased risk of developing de novo post-transplant malignancies (PTMs), with regional differences in types with excess risk compared to the general population. A single-center, population-controlled, retrospective cohort study was conducted at a tertiary care center in Thailand among all adults who underwent their first kidney transplant from 1986 to 2018. Standardized incidence ratios (SIRs) of malignancy by age, sex, and place of residence were obtained using data from the National Cancer Registry of Thailand as population control. There were 2,024 KTRs [mean age, 42.4 years (SD 11.4); female patients, 38.6%] during 16,495 person-years at risk. Of these, 125 patients (6.2%) developed 133 de novo PTMs. The SIR for all PTMs was 3.85 (95% CI 3.22, 4.56), and for pooled solid and hematologic PTMs, it was 3.32 (95% CI 2.73, 3.99). Urothelial malignancies had the largest excess risk, especially in women [female SIR 114.7 (95% CI 66.8, 183.6); male SIR 17.5 (95% CI 8.72, 31.2)]. The next two most common cancers were non-Hodgkin's lymphoma and skin cancer [SIR 20.3 (95% CI 13.6, 29.1) and 24.7 (95% CI 15.3-37.8), respectively]. Future studies are needed to identify the risk factors and assess the need for systematic screening among PTMs with excess risk in KTRs.


Subject(s)
Kidney Transplantation , Neoplasms , Skin Neoplasms , Adult , Humans , Male , Female , Kidney Transplantation/adverse effects , Thailand/epidemiology , Incidence , Retrospective Studies , Population Control , Neoplasms/epidemiology , Neoplasms/etiology , Skin Neoplasms/epidemiology , Risk Factors , Transplant Recipients
2.
Sci Rep ; 13(1): 19119, 2023 11 05.
Article in English | MEDLINE | ID: mdl-37926743

ABSTRACT

Death and end-stage kidney disease (ESKD) are major outcomes of glomerular disease. (GD) The years of potential life lost (YLL) may provide additional insight into the disease burden beyond death rates. There is limited data on premature mortality in GD. In this retrospective observational cohort study, we evaluated the mortality, ESKD rates, and YLL in Thais with biopsy-proven GD. The mortality and combined outcome rates were determined by log-rank test and ESKD by using a competing risk model. YLL and premature life lost before age 60 were calculated for different GD based on the life expectancy of the Thai population. Patients with GD (n = 949) were followed for 5237 patient years. The death rate and ESKD rates (95%CI) were 4.2 (3.7-4.9) and 3.3 (2.9-3.9) per 100 patient-years, respectively. Paraprotein-related kidney disease had the highest death rate, and diabetic nephropathy had the highest ESKD rate. Despite not having the highest death rate, lupus nephritis (LN) had the highest YLL (41% of all GD) and premature loss of life before age 60. In conclusion, YLL provided a different disease burden assessment compared to mortality rates and identified LN as the major cause of premature death due to GD in a Southeast Asian cohort.


Subject(s)
Glomerulonephritis , Kidney Failure, Chronic , Life Expectancy , Mortality, Premature , Humans , Middle Aged , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/mortality , Lupus Nephritis/epidemiology , Retrospective Studies , Southeast Asian People/statistics & numerical data , Glomerulonephritis/complications , Glomerulonephritis/mortality
4.
World J Hepatol ; 13(8): 853-867, 2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34552692

ABSTRACT

Utilizing kidneys from donors with hepatitis B is one way to alleviate the current organ shortage situation. However, the risk of hepatitis B virus (HBV) transmission remains a challenge that undermines the chance of organs being used. This is particularly true with hepatitis B surface antigen (HBsAg) positive donors despite the comparable long-term outcomes when compared with standard donors. To reduce the risk of HBV transmission, a comprehensive approach is needed. This includes assessment of donor risk, optimal allocation to the proper recipient, appropriate immunosuppressive regimen, optimizing the prophylactic therapy, and post-transplant monitoring. This review provides an overview of current evidence of kidney transplants from donors with HBsAg positivity and outlines the challenge of this treatment. The topics include donor risk assessment by adopting the nucleic acid test coupled with HBV DNA as the HBV screening, optimal recipient selection, importance of hepatitis B immunity, role of nucleos(t)ide analogues, and hepatitis B immunoglobulin. A summary of reported long-term outcomes after kidney transplantation and proposed criteria to utilize kidneys from this group of donors was also defined and discussed.

5.
PLoS One ; 16(6): e0252638, 2021.
Article in English | MEDLINE | ID: mdl-34081719

ABSTRACT

Mesangial C4d deposits have been associated with worse outcomes in Western patients with IgA nephropathy (IgAN), but there is limited data in Asians. Previously, a high proportion of stained glomeruli was often required for the classification of C4d positive (C4d+ve). Positive staining in lower proportion of staining would be classified as C4d-ve. This retrospective study evaluated the prognostic value of C4d+ve using a less stringent definition (one C4d+ve glomerulus) in Thai patients with IgAN (n = 120). Baseline findings and outcomes were compared between those with more extensive C4d staining patterns and those with more restricted staining. Clinico-pathologic parameters and risk for kidney outcomes (kidney failure or decline GFR50%) were compared between C4d+ve versus C4d-ve, and between different patterns: Focal (< 50%) versus Diffuse (≥ 50% of glomeruli); or Global (≥ 50) versus Segmental (< 50% of mesangial area). The hazard ratios were estimated using Cox proportional hazard models for Model 1 (Oxford score+ C4d) and Model 2 (Model 1+ clinical factors). C4d+ve (n = 81) had lower eGFR, more global sclerosis, and interstitial fibrosis than C4d-ve at baseline. The 5-year kidney survival for C4d+ve was lower (53.7%) than C4d-ve (89.7%); P = 0.0255. By univariate analysis, T1, T2, C4d+ve, eGFR<60, proteinuria were predictors of kidney outcome. By multivariate analysis, proteinuria, T1, T2 and C4d+ve were independent predictors (Model 2 HR (95% CI) C4d+ve: 3.24 (1.09-9.58), p = 0.034). Segmental had lower eGFR, higher tubulointerstitial fibrosis, and segmental sclerosis compared to Global pattern. Clinicopathological parameters were not different between Focal and Diffuse patterns. Outcomes were similar between staining patterns. In conclusion, C4d staining may be a valuable marker of poor prognosis in Asian patients with IgAN. Less stringent criteria for C4d+ve should be considered as no differences in outcomes were observed between more extensive staining with less extensive patterns. More studies are needed to identify the optimum criteria for C4d+ve.


Subject(s)
Complement C4b/metabolism , Glomerular Mesangium/metabolism , Glomerulonephritis, IGA/diagnosis , Renal Insufficiency/diagnosis , Adult , Female , Glomerular Filtration Rate , Glomerular Mesangium/pathology , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/pathology , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , Proteinuria/complications , Renal Insufficiency/etiology , Retrospective Studies , Risk Factors , Severity of Illness Index , Thailand , Young Adult
6.
BMC Res Notes ; 13(1): 417, 2020 Sep 05.
Article in English | MEDLINE | ID: mdl-32891182

ABSTRACT

OBJECTIVE: Perioperative change of hemoglobin concentration (Hb) was associated with acute kidney injury in patients who underwent non-cardiac surgery, but has never been investigated in kidney transplant patients. This study aimed to observe the effects of perioperative Hb change on early graft function in kidney transplant recipients. RESULTS: A total of 269 kidney transplant patients were enrolled, of whom 98 (36.4%) developed poor early graft function (PEGF), and 171 (63.6%) had immediate graft function. Comparing two groups, patients with PEGF had a greater decremental change of Hb (-1.60 [-2.38,-0.83] vs. -0.70 [-1.35,0.20] g/dL, respectively; p < 0.001). A Hb cut-point of -1.35 g/dL was obtained from ROC analysis. Multivariate analysis showed that perioperative Hb decrement greater than 1.35 g/dL was an independent risk of PEGF (adjusted OR of 2.52, 95% CI 1.11-5.72; p = 0.026). Subgroup analysis revealed deceased donor kidney transplant (DDKT; n = 126) (adjusted OR of 2.89, 95% CI 1.11-7.55; p = 0.029), but not living donor kidney transplantation (LDKT; n = 143) (adjusted OR of 1.68, 95% CI 0.23-12.15; p = 0.606), was influenced by the perioperative Hb decrement. In conclusion, this study suggests that decremental change in perioperative Hb greater than 1.35 g/dL may serve as a modifiable factor of PEGF in DDKT.


Subject(s)
Kidney Transplantation , Hemoglobins , Humans , Kidney , Kidney Transplantation/adverse effects , Tissue Donors
7.
BMC Anesthesiol ; 20(1): 215, 2020 08 27.
Article in English | MEDLINE | ID: mdl-32854613

ABSTRACT

BACKGROUND: Volatile anesthetic agents used during surgery have immunomodulatory effects which could affect postoperative outcomes. Recognizing that regulatory T cells (Tregs) plays crucial roles in transplant tolerance and high peripheral blood Tregs associated with stable kidney graft function, knowing which volatile anesthetic agents can induce peripheral blood Tregs increment would have clinical implications. This study aimed to compare effects of desflurane and sevoflurane anesthesia on peripheral blood Tregs induction in patients undergoing living donor kidney transplantation. METHODS: A prospective, randomized, double-blind trial in living donor kidney transplant recipients was conducted at a single center, tertiary-care, academic university hospital in Thailand during August 2015 - June 2017. Sixty-six patients were assessed for eligibility and 40 patients who fulfilled the study requirement were equally randomized and allocated to desflurane versus sevoflurane anesthesia during transplant surgery. The primary outcome included absolute changes of peripheral blood CD4+CD25+FoxP3+Tregs which measured by flow cytometry and expressed as the percentage of the total population of CD4+ T lymphocytes at pre-exposure (0-h) and post-exposure (2-h and 24-h) to anesthetic gas. P-value < 0.05 denoted statistical significance. RESULTS: Demographic data were comparable between groups. No statistical difference of peripheral blood Tregs between desflurane and sevoflurane groups observed at the baseline pre-exposure (3.6 ± 0.4% vs. 3.1 ± 0.4%; p = 0.371) and 2-h post-exposure (3.0 ± 0.3% vs. 3.5 ± 0.4%; p = 0.319). At 24-h post-exposure, peripheral blood Tregs was significantly higher in desflurane group (5.8 ± 0.5% vs. 4.1 ± 0.3%; p = 0.008). Within group analysis showed patients receiving desflurane, but not sevoflurane, had 2.7% increase in peripheral blood Treg over 24-h period (p < 0.001). CONCLUSION: This study provides the clinical trial-based evidence that desflurane induced peripheral blood Tregs increment after 24-h exposure, which could be beneficial in the context of kidney transplantation. Mechanisms of action and clinical advantages of desflurane anesthesia based on Treg immunomodulation should be investigated in the future. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02559297 . Registered 22 September 2015 - retrospectively registered.


Subject(s)
Anesthetics, Inhalation/administration & dosage , Desflurane/administration & dosage , Kidney Transplantation/methods , Living Donors , Sevoflurane/administration & dosage , T-Lymphocytes, Regulatory/drug effects , Adult , Anesthetics, Inhalation/immunology , Desflurane/immunology , Double-Blind Method , Female , Humans , Kidney Transplantation/trends , Male , Middle Aged , Prospective Studies , Sevoflurane/immunology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism
8.
Drug Metab Pharmacokinet ; 35(1): 139-144, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31727575

ABSTRACT

Available data of early conversion from twice-daily tacrolimus (TAC-BID) to once-daily tacrolimus (TAC-OD) in de novo kidney transplant (KT) recipients are limited. We conducted a prospective study of early conversion to TAC-OD in de novo KT recipients. Eligible patients were enrolled to receive TAC-BID (Prograf®) and then converted to TAC-OD (Advagraf®) by 1:1 ratio, approximately 14 days after KT (range 9-22). Blood samples were investigated for pharmacokinetic parameters before and 7-14 days after the conversion. Fifteen patients were included and provided AUC0-24 of 202.9 ± 44.4 ng h/mL for TAC-BID (pre-conversion) and 193.0 ± 63.4 ng h/mL for TAC-OD (post-conversion) (p = 0.41). Mean trough blood concentration (Cmin) of TAC-BID and TAC-OD was 6.4 ± 1.4 ng/mL and 4.9 ± 1.6 ng/mL (p = 0.01). Correlation coefficient (r) between Cmin and AUC0-24 of TAC-BID and TAC-OD were 0.620 and 0.875. Additional analysis found that patients with a drop of Cmin > 30% had a significant lower AUC0-24 after conversion. Renal function remains stable. We conclude that early conversion to TAC-OD is safe and well tolerated with an indifferent systemic exposure. However, patients with a drop of Cmin > 30% after conversion to TAC-OD will require additional dose adjustment.


Subject(s)
Kidney Transplantation , Tacrolimus/pharmacokinetics , Adult , Drug Administration Schedule , Drug Compounding , Drug Monitoring , Female , Humans , Kidney Function Tests , Male , Prospective Studies , Tacrolimus/administration & dosage , Tacrolimus/blood
9.
Ther Drug Monit ; 40(5): 549-557, 2018 10.
Article in English | MEDLINE | ID: mdl-29878980

ABSTRACT

BACKGROUND: Tacrolimus, a critical dose drug, is widely used in transplantation. Knowing the contribution of genetic factors, which significantly influence tacrolimus variability, is beneficial in the personalization of its starting dose. The significant impact of CYP3A5*3 polymorphisms on tacrolimus exposure has been reported. Conflicting results of the additional influence of POR*28 polymorphisms on tacrolimus pharmacokinetic interindividual variability have been observed among different populations. The objective of this study was to explore the interaction between POR*28 and CYP3A5*3 polymorphisms and their main effects on tacrolimus trough concentration to dose ratios on day 7 after kidney transplantation. METHODS: Two hundred sixteen adult kidney transplant recipients participated in this retrospective study. All participants received a twice daily tacrolimus regimen. Blood samples and data were collected on day 7 after transplantation. A 2-way analysis of covariance was performed. Tested covariates were age, hemoglobin, serum albumin, and prednisolone dose. RESULTS: A 2 × 2 analysis of covariance revealed that the interaction between CYP3A5 polymorphisms (CYP3A5 expresser and CYP3A5 nonexpresser) and POR polymorphisms (POR*28 carrier and POR*28 noncarrier) was not significant (F(1, 209) = 2.473, P = 0.117, (Equation is included in full-text article.)= 0.012). The predicted main effect of CYP3A5 and POR polymorphisms was significant (F(1, 209) = 105.565, P < 0.001, (Equation is included in full-text article.)= 0.336 and F(1, 209) = 4.007, P = 0.047, (Equation is included in full-text article.)= 0.019, respectively). Hemoglobin, age, and steroid dose influenced log C0/dose of tacrolimus (F(1, 209) = 20.612, P < 0.001, (Equation is included in full-text article.)= 0.090; F(1, 209) = 14.360, P < 0.001, (Equation is included in full-text article.)= 0.064; and F(1, 209) = 5.512, P = 0.020, (Equation is included in full-text article.)= 0.026, respectively). CONCLUSIONS: After adjusting for the influences of hemoglobin, age, and prednisolone dose, significant impacts of the CYP3A5 and POR polymorphisms on tacrolimus exposure were found. The effect of POR*28 and CYP3A5*3 polymorphisms during the very early period after kidney transplantation is independent of each other.


Subject(s)
Cytochrome P-450 CYP3A/genetics , Cytochrome P-450 Enzyme System/genetics , Kidney Transplantation , Polymorphism, Genetic , Tacrolimus/pharmacokinetics , Adult , Dose-Response Relationship, Drug , Female , Gene Frequency , Genotype , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Male , Middle Aged , Postoperative Period , Tacrolimus/blood , Time Factors , Young Adult
10.
Int Urol Nephrol ; 50(2): 355-364, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29236239

ABSTRACT

PURPOSE: Vascular calcification is common in chronic kidney disease (CKD) and predicts poor patient outcomes. While computed tomography is the gold standard for evaluation of vascular calcification, plain radiograph offers a simpler and less costly alternative. The calcification of abdominal aorta, iliac and femoral arteries has been evaluated by plain radiograph, but the data on their outcome predictabilities are still limited. The present study investigated the role of abdominal aortic calcification (AAC) and pelvic arterial calcification (PAC) in predicting overall morality in non-dialysis CKD stages 2-5 (CKD 2-5), maintenance hemodialysis (HD) and long-term kidney transplant (KT) patients. METHODS: Four hundred and nineteen patients were included. Lateral abdominal and pelvic radiographs were obtained. The degree of AAC and PAC was evaluated according to the methods described previously by Kaupplia et al. and Adragao et al. Patients were followed prospectively for 5 years. RESULTS: AAC and PAC scores correlated well with the correlation coefficients of 0.442 for CKD 2-5, 0.438 for HD and 0.586 for KT (p < 0.001). Patients with AAC score > 6 or PAC score > 1 were older, showed higher prevalence of DM and had higher serum phosphate and PTH but lower serum albumin and eGFR. A more severe degree of AAC was associated with an increase in KT duration, whereas a more severe degree of PAC was associated with worsening kidney function and prolonged dialysis vintage. Kaplan-Meier survival curves revealed AAC score > 6 as a significant predictor of all-cause mortality in CKD 2-5 but not in HD or KT, whereas PAC score > 1 was a significant predictor of all-cause mortality in all three populations. After adjusting for age, the predictability of AAC was lost, whereas PAC remained an independent predictor of mortality in all three populations. Adjustments for cardiovascular and CKD risk factors including age, gender, BMI, DM, serum albumin, calcium and phosphate attenuated the predictability of PAC in HD but not in CKD 2-5 or KT patients. CONCLUSION: PAC was better than AAC in predicting mortality in CKD, HD and KT patients.


Subject(s)
Aorta, Abdominal , Femoral Artery , Iliac Artery , Kidney Transplantation/adverse effects , Radiography/methods , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic , Vascular Calcification , Adult , Aged , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/pathology , Female , Femoral Artery/diagnostic imaging , Femoral Artery/pathology , Humans , Iliac Artery/diagnostic imaging , Iliac Artery/pathology , Kidney Transplantation/methods , Long Term Adverse Effects/diagnosis , Male , Middle Aged , Predictive Value of Tests , Renal Dialysis/methods , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/therapy , Severity of Illness Index , Thailand/epidemiology , Vascular Calcification/diagnosis , Vascular Calcification/etiology
11.
Int J Clin Pharm ; 39(6): 1298-1303, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29101615

ABSTRACT

Background Early conversion from twice-daily tacrolimus (TAC-BID) to once-daily tacrolimus (TAC-OD) provides a greater benefit of reducing under-exposure of TAC-OD during the first period after transplantation. Information regarding the conversion dose among Asian kidney transplant recipients is still limited. Objective This study aimed to compare the trough levels (Cmin) of TAC-BID (Prograf®) and TAC-OD (Advagraf®). The values were obtained from early conversion intervention by 1:1 milligram per-milligram. Setting A university-based hospital. Method This study employed a single-center, open-label, prospective and single-armed design. Fifteen de novo standard risk kidney transplant recipients were enrolled. Fourteen days after transplantation, the Cmin of TAC-BID (pre-conversion Cmin) was determined. Subsequently, TAC-BID was converted to TAC-OD with a similar dose. The Cmin of TAC-OD was first measured at a steady state (immediate post-conversion Cmin) and compared. All enrolled patients received therapeutic monitoring at the first and second months. Main outcome measure Pre-conversion Cmin of TAC-BID and immediate post-conversion Cmin of TAC-OD. Results The immediate post-conversion Cmin was found to be 23% lowered than the pre-conversion Cmin. However, the Cmin of TAC-OD was found to be similar to the pre-conversion Cmin compared during the follow-up period. Renal function was found to be stable in all patients over 2 months. Conclusion Early conversion therapy was associated with a significantly lower immediate post-conversion Cmin but comparable Cmin throughout the follow-up period. The "one to one conversion ratio" from TAC-BID to TAC-OD could be performed among Asian de novo kidney transplant recipients at an early period after transplantation.


Subject(s)
Kidney Transplantation/methods , Tacrolimus/pharmacokinetics , Drug Administration Schedule , Female , Hospitals, University , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacokinetics , Male , Prospective Studies , Tacrolimus/blood
12.
Transpl Infect Dis ; 19(6)2017 Dec.
Article in English | MEDLINE | ID: mdl-28805990

ABSTRACT

JC polyomavirus (JCPyV)-associated nephropathy (JCPyVAN) occurs in <3% of PVAN cases after renal transplantation. We report the first confirmed case to our knowledge of JCPyVAN diagnosed by kidney biopsy in the early 6 months post transplant in Thailand. In this case report, recovery of renal allograft function was not observed after reduction of immunosuppressive agents and administration of intravenous immunoglobulin and cidofovir. Despite persistent JCPyV viruria, no significant further decline in allograft function was documented at 15 months post transplant.


Subject(s)
Allografts/virology , JC Virus/isolation & purification , Kidney Diseases/virology , Kidney Transplantation/adverse effects , Kidney/virology , Postoperative Complications/virology , Adult , Allografts/pathology , Biopsy , Creatinine/blood , Graft Rejection/prevention & control , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/adverse effects , Kidney/pathology , Kidney Diseases/blood , Kidney Diseases/drug therapy , Kidney Diseases/urine , Kidney Failure, Chronic/surgery , Male , Polyomavirus Infections/blood , Polyomavirus Infections/drug therapy , Polyomavirus Infections/urine , Polyomavirus Infections/virology , Postoperative Complications/blood , Postoperative Complications/drug therapy , Postoperative Complications/urine , Time Factors , Tumor Virus Infections/blood , Tumor Virus Infections/drug therapy , Tumor Virus Infections/urine , Tumor Virus Infections/virology
13.
J Med Assoc Thai ; 100(2): 133-41, 2017 Feb.
Article in English | MEDLINE | ID: mdl-29916232

ABSTRACT

Objective: To identify the prevalence and risk factors of peripheral arterial disease (PAD) in dialysis patients covering both hemodialysis and peritoneal dialysis. Material and Method: All consecutive cases of stable dialysis patients in Ramathibodi hospital from September 2013 to December 2013 were surveyed. Patients were classified as having PAD if they had ankle-brachial blood pressure index (ABI) values of ≤0.9 or >1.4. We also measured toe-brachial blood pressure index (TBI) and TBI ≤0.6 was classified as abnormal TBI. Data were analyzed to identify the prevalence and risk factors of PAD. Results: Among these 269 stable dialysis patients, the mean age was 48.8±15.1 years and 56.9% were male. The mean dialysis vintage was 52.6±41.8 months. The prevalence of PAD was 11.5% and the prevalence of abnormal TBI was 29.7%. Multivariate regression analysis found that increased body mass index (BMI), history of coronary artery disease (CAD), and increased pulse pressure were associated with PAD. Conclusion: The prevalence of PAD among long-term stable dialysis patients in Thailand was around one-tenth. The prevalence of abnormal TBI was higher than those of abnormal ABI criteria. Factors associated with PAD were increased BMI, history of CAD, and increased pulse pressure.


Subject(s)
Peripheral Arterial Disease/epidemiology , Renal Dialysis , Ankle Brachial Index , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Risk Factors , Thailand/epidemiology
14.
Clin Exp Nephrol ; 21(5): 926-931, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27981393

ABSTRACT

BACKGROUND: After kidney transplantation, fibroblast growth factor-23 (FGF-23) normally returns to baseline within 1 year whereas hyperparathyroidism persists in most kidney transplant (KT) recipients. As a result, serum phosphate remains relatively low in association with increased serum calcium and urinary phosphate excretion when compared to chronic kidney disease patients. The relationship between mineral metabolism and outcomes in long-term KT recipients has not been extensively studied. This study investigated whether the alteration in mineral metabolism influenced graft survival in long-term KT recipients. METHODS: This study included 273 KT recipients after 1 year of transplantation. Mineral parameters were obtained at the time of enrolment and patients were followed prospectively for an average of 71 months. RESULTS: Graft loss (death-censored) occurred in 41 (15%) patients. In univariate analysis, deceased donor transplantation, decreased serum albumin and estimated glomerular filtration rate, increased serum phosphate, parathyroid hormone (PTH), FGF-23 and fractional excretion of phosphate (FePi) predicted future allograft loss. After adjustments for cardiovascular disease risk factors, donor type, dialysis vintage, serum albumin and allograft function, only increased PTH and FePi remained associated with the outcome. Relationships between increased serum phosphate and FGF-23 with graft survival were lost after adjustments. Adjusted survival curves revealed the association between PTH > 90 pg/mL and FePi > 20% with worse graft survival. CONCLUSIONS: Hyperparathyroidism and increased FePi predicted allograft loss in long-term KT recipients.


Subject(s)
Graft Survival , Hyperparathyroidism/etiology , Hypophosphatemia, Familial/etiology , Hypophosphatemia/etiology , Kidney Transplantation/adverse effects , Kidney/physiopathology , Phosphates/urine , Renal Elimination , Adult , Allografts , Female , Fibroblast Growth Factor-23 , Glomerular Filtration Rate , Humans , Hyperparathyroidism/blood , Hyperparathyroidism/diagnosis , Hyperparathyroidism/physiopathology , Hypophosphatemia/blood , Hypophosphatemia/diagnosis , Hypophosphatemia/physiopathology , Hypophosphatemia, Familial/diagnosis , Hypophosphatemia, Familial/physiopathology , Hypophosphatemia, Familial/urine , Male , Middle Aged , Phosphates/blood , Prospective Studies , Renal Dialysis , Risk Factors , Time Factors , Treatment Outcome
15.
World J Transplant ; 6(4): 712-718, 2016 Dec 24.
Article in English | MEDLINE | ID: mdl-28058222

ABSTRACT

AIM: To evaluate and compare the outcomes of kidney transplant (KT) from deceased donors among standard criteria, acute kidney injury (AKI) and expanded criteria donors (ECDs). METHODS: This retrospective study included 111 deceased donor kidney transplant recipients (DDKT). Deceased donors were classified as standard criteria donor (SCD), AKI donor and ECD. AKI was diagnosed and classified based on change of serum Cr by acute kidney injury network (AKIN) criteria. Primary outcome was one-year estimated glomerular filtration rate (eGFR) calculated from Cr by CKD-EPI. Multivariate regression analysis was done by adjusting factors such as type of DDKT, %Panel-reactive antibodies, cold ischemic time, the presence of delayed graft function and the use of induction therapy. Significant factors that can affect the primary outcomes were then identified. RESULTS: ECD group had a significantly lower eGFR at one year (33.9 ± 17.3 mL/min) when compared with AKI group (56.6 ± 23.9) and SCD group (63.6 ± 19.9) (P < 0.001). For AKI group, one-year eGFR was also indifferent among AKIN stage 1, 2 or 3. Patients with AKIN stage 3 had progressive increase of eGFR from 49.6 ± 27.2 at discharge to 61.9 ± 29.0 mL/min at one year. From Kaplan-Meier analysis, AKI donor showed better two-year graft survival than ECD (100% vs 88.5%, P = 0.006). Interestingly, AKI group had a stable eGFR at one and two year. The two-year eGFR of AKI group was not significantly different from SCD group (56.6 ± 24.5 mL/min vs 58.6 ± 23.2 mL/min, P = 0.65). CONCLUSION: Kidney transplantations from deceased donors with variable stage of acute kidney injuries were associated with favorable two-year allograft function. The outcomes were comparable with KT from SCD. This information supports the option that deceased donors with AKI are an important source of organ for kidney transplantation even in the presence of stage 3 AKI.

16.
Eur J Clin Pharmacol ; 72(3): 277-83, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26635230

ABSTRACT

PURPOSE: The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized tacrolimus regimen. METHODS: A total of 164 patients participated in the study. All received oral tacrolimus twice daily starting on the day of surgery with the target pre-dose (trough) concentration of 4-8 ng/ml for prevention of allograft rejection. Cytochrome P450 (CYP) 3A5 genotypes were determined. The patients were divided into CYP3A5 expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (homozygous CYP3A5*3). Whole blood tacrolimus concentrations on days 3 and 7 posttransplantation and the incidence of biopsy-proven acute rejection (BPAR) at 3-month posttransplantation were compared between groups. RESULTS: On day 3, the median (IQR) dose-and-weight-normalized trough concentration in expressers and nonexpressers were 54.61 (31.98, 78.87) and 91.80 (57.60, 130.20) ng/ml per mg/kg/day, respectively (p < 0.001). Although only 47 and 42% of expressers and nonexpressers were within the target range on day 3, approximately 60% of both groups were within the target range on day 7. Proportions of BPAR among expressers and nonexpressers were 6.0 and 7.4 %, respectively (p = 0.723). The median (IQR) times to the first rejection in CYP3A5 expressers and nonexpressers were 32 (12, 68) and 15 (12, 37) days, respectively (p = 0.410). CONCLUSIONS: Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP3A5 polymorphism on BPAR was not observed in this study.


Subject(s)
Cytochrome P-450 CYP3A/genetics , Immunosuppressive Agents/blood , Kidney Transplantation , Tacrolimus/blood , Adult , Female , Graft Rejection/blood , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Polymorphism, Genetic , Tacrolimus/pharmacokinetics , Tacrolimus/therapeutic use
17.
Nephrology (Carlton) ; 20(3): 177-83, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25492162

ABSTRACT

AIM: To report the kidney transplant activity and survival data during the past 25 years from the Thai Transplant Registry. METHODS: By using the registry database that was collected and updated yearly by 26 transplant centres across the country, we have reported the donor, recipient, and transplant characteristics during the past 25 years from 1987 to 2012. The primary outcome was graft loss that was defined as return to dialysis, graft removal, retransplant, or patient death. RESULTS: 465 kidney transplants were performed in 2012, an 8.1% and 23.0% increase in living and deceased donor transplants compared to the previous year, respectively. Between 1987 and 2012 with the data of 3808 recipients, patient survival and graft survival improved significantly. Traffic accident was the most common cause of death in brain-dead donors. Additionally, the most common cause of end-stage kidney disease was glomerulonephritis. Infection has been among the most common causes of death in kidney transplant recipients. CONCLUSION: We have reported the total number, the graft and the patient survival data of kidney transplant recipients in Thailand for the period from 1987 to 2012. Although the number of patients is much lower than that in the developed countries, the patients and the graft survival rates are comparable.


Subject(s)
Graft Rejection/prevention & control , Graft Survival , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Female , Graft Rejection/immunology , Graft Rejection/mortality , Humans , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/mortality , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Middle Aged , Registries , Renal Dialysis , Reoperation , Retrospective Studies , Risk Factors , Thailand/epidemiology , Time Factors , Tissue Donors/supply & distribution , Tissue and Organ Procurement , Treatment Outcome , Young Adult
18.
Blood Purif ; 37(1): 33-8, 2014.
Article in English | MEDLINE | ID: mdl-24503711

ABSTRACT

BACKGROUND: Bone loss is common among hemodialysis patients and contributes to mortality. The association between bone loss and vascular calcification may explain the increased mortality risk. Studies on the association between decreased bone mass and mortality in maintenance hemodialysis patients are limited. METHODS: Eighty-three hemodialysis patients underwent bone mineral density (BMD) and coronary artery calcification (CAC) measurements. The relationship between BMD and mortality was analyzed after a 5-year follow-up period. RESULTS: Eighty percent of the patients had reduced hip BMD. In univariate Cox regression analyses, age, cardiovascular disease, dyslipidemia, increased CAC score, increased comorbidity score and decreased hip BMD were associated with mortality. Low hip BMD remained independently associated with mortality after adjustments for cardiovascular risk factors, comorbidity score and CAC score. Patients with BMD in the lowest tertile had the worst survival. CONCLUSION: Low hip BMD predicted mortality in maintenance hemodialysis patients independent of CAC.


Subject(s)
Bone Density , Bone Diseases, Metabolic/complications , Hip/physiopathology , Kidney Failure, Chronic/therapy , Renal Dialysis/mortality , Aged , Bone Diseases, Metabolic/physiopathology , Calcinosis/complications , Calcinosis/pathology , Coronary Artery Disease/complications , Coronary Artery Disease/pathology , Coronary Vessels/pathology , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/mortality , Male , Middle Aged , Risk Factors , Treatment Outcome
19.
Nephrology (Carlton) ; 19(4): 251-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24447254

ABSTRACT

AIM: Vascular calcification (VC) is common among patients with chronic kidney disease (CKD) due to the strong prevalence of cardiovascular and CKD-related risk factors such as diabetes mellitus (DM), hypertension and phosphate retention. Kidney transplantation improves kidney function and abnormal mineral metabolism at the same time. It remains unclear whether kidney transplantation favourably impacts VC in the long-term. METHODS: The present study examined VC in 132 kidney transplant (KT) recipients who had been transplanted for longer than one year. The severity of VC was compared to 129 CKD stages 5-5D patients on a kidney transplant (KT) waiting list. RESULTS: The median KT vintage was 88 months. The prevalence of VC among KT and CKD patients were 54.5% and 62.8%, respectively, (P = 0.2). There were no differences in age, gender, body mass index (BMI), the prevalence of DM or CVD between the two groups. Among patients with calcification, a more severe degree was observed in KT recipients (P = 0.01). Aging, DM, CVD and dialysis vintage were associated with significant VC in both groups. The degree of VC in KT recipients was more pronounced than that in CKD patients among those who experienced prolonged dialysis vintage (>2 years) (P = 0.04). Among KT recipients, the severity of VC increased with the length of time after transplantation and became more substantial after 5 years. CONCLUSIONS: Long-term KT recipients demonstrated a more severe degree of VC compared to matched CKD stages 5-5D patients. The severity of VC became more pronounced among those with longer transplant vintage and was in part influenced by past dialysis experience.


Subject(s)
Kidney Transplantation/adverse effects , Renal Insufficiency, Chronic/surgery , Vascular Calcification/epidemiology , Adult , Female , Humans , Male , Middle Aged , Prevalence , Renal Dialysis/adverse effects , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Severity of Illness Index , Thailand/epidemiology , Time Factors , Treatment Outcome , Vascular Calcification/diagnosis , Waiting Lists
20.
Nephrology (Carlton) ; 19(1): 11-20, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23876069

ABSTRACT

Lupus nephritis (LN) is a common and important manifestation of systemic lupus erythematosus (SLE). Evidence suggests higher rates of lupus renal involvement in Asian populations, and maybe more severe nephritis, compared with other racial or ethnic groups. The management of LN has evolved considerably over the past three decades, based on observations from clinical studies that investigated different immunosuppressive agents including corticosteroids, cyclophosphamide, azathioprine, mycophenolic acid, calcineurin inhibitors and novel biologic therapies. This is accompanied by improvements in both the short-term treatment response rate and long-term renal function preservation. Treatment guidelines for LN have recently been issued by rheumatology and nephrology communities in U.S.A. and Europe. In view of the racial difference in disease manifestation and response to therapy, and the substantial disease burden in Asia, a panel of 15 nephrologists and rheumatologists from different Asian regions with extensive experience in lupus nephritis - the Steering Group for the Asian Lupus Nephritis Network (ALNN) - met and discussed the management of lupus nephritis in Asian patients. The group has also reviewed and deliberated on the recently published recommendations from other parts of the world. This manuscript summarizes the discussions by the group and presents consensus views on the clinical management and treatment of adult Asian patients with LN, taking into account both the available evidence and expert opinion in areas where evidence remains to be sought.


Subject(s)
Lupus Nephritis/therapy , Practice Guidelines as Topic , Asia , Cyclophosphamide/therapeutic use , Humans , Immunosuppression Therapy , Lupus Nephritis/classification , Lupus Nephritis/immunology , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use
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