Hyperchloremic metabolic acidosis after plasma exchange in a patient with renal transplant rejection: A case report.

Therapeutic plasma exchange (TPE) is an effective treatment for several renal disorders, including renal transplant rejection. However, repeated plasma exchanges can result in various metabolic disturbances and complications. We present a 61-year old male with a medical history of type 2 diabetes, hypertension, successfully treated multiple myeloma, and a post-mortem kidney transplantation 7 months prior to presentation. The patient was hospitalized with an antibody-mediated transplant rejection for which treatment with methylprednisolone, TPE with a 40 g/L albumin solution as a replacement fluid, and intravenous immunoglobulins was initiated. After four TPE treatments, the patient developed gastrointestinal complaints and muscle weakness. Despite daily oral bicarbonate supplementation, laboratory tests revealed a hyperchloremic metabolic acidosis: bicarbonate 11.7 mmol/L, chloride 111 mmol/L, and sodium 138 mmol/L. Metabolic acidosis due to citrate accumulation was ruled out with a normal total-to-ionized calcium ratio. After treatment with intravenous bicarbonate supplementation, the symptoms disappeared. Analysis of the albumin solution showed a chloride concentration of 132 mmol/L. This is the first case that describes severe metabolic acidosis after multiple sessions of TPE with an albumin solution in a patient with impaired renal function. The hyperchloremic metabolic acidosis is the result of administration of large volumes of an albumin solution with high chloride concentrations. Special attention should be paid to the acid-base balance during TPE in patients with impaired renal function. Future research should investigate the incidence of hyperchloremic metabolic acidosis during TPE in patients with impaired renal function.

Targeted changes in blood lipids improves fibrosis in renal allografts.

BACKGROUND: Chronic interstitial fibrosis is the primary barrier against the long-term survival of transplanted kidneys. Extending the lifespan of allografts is vital for ensuring the long-term health of patients undergoing kidney transplants. However, few targets and their clinical applications have been identified. Moreover, whether dyslipidemia facilitates fibrosis in renal allograft remains unclear. METHODS: Blood samples were collected from patients who underwent kidney transplantation. Correlation analyses were conducted between the Banff score and body mass index, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. A rat model of renal transplantation was treated with the lipid-lowering drug, fenofibrate, and kidney fibrosis levels were determined by histochemical staining. Targeted metabolomic detection was conducted in blood samples from patients who underwent kidney transplantation and were divided into fibrotic and non-fibrotic groups. Rats undergoing renal transplantation were fed either an n-3 or n-6 polyunsaturated fatty acid (PUFA)-enriched diet. Immunohistochemical and Masson's trichrome staining were used to determine the degree of fibrosis. RESULTS: Hyperlipidemia was associated with fibrosis development. Treatment with fenofibrate contributed to improve fibrosis in a rat model of renal transplantation. Moreover, n-3 PUFAs from fibrotic group showed significant downregulation compared to patients without fibrotic renal allografts, and n-3 PUFAs-enriched diet contributed to delayed fibrosis in a rat model of renal transplantation. CONCLUSIONS: This study suggests that hyperlipidemia facilitates fibrosis of renal allografts. Importantly, a new therapeutic approach was provided that may delay chronic interstitial fibrosis in transplanted kidneys by augmenting the n-3 PUFA content in the diet.

Safety and effectiveness of tigecycline combination therapy in renal transplant patients with infection due to carbapenem-resistant gram-negative bacteria.

Background: Carbapenem-resistant gram-negative bacterial (CRGNB) infections are increasing among kidney transplant recipients, and effective therapeutic options are limited. This study aimed to investigate the efficacy and adverse events associated with combination therapy tigecycline in renal transplant patients with CRGNB infections. Methods: This study retrospectively analyzed 40 Chinese patients with confirmed or suspected CRGNB infections who received tigecycline therapy. The patients' case features and clinical and microbiological data were analyzed. Results: A total of 40 renal transplant recipients received tigecycline therapy for a median duration of 9 (range, 3-25) days. CRGNB isolates were obtained from the organ preservation solution of the donor kidney in 28 patients, with confirmed transmission in 4 patients. Infections were detected in the bloodstream, urinary tract, sputum, and wound. The most prevalent isolates were Klebsiella pneumoniae (75%, 30/40), Acinetobacter baumannii (15%, 6/40), and Escherichia coli (10%, 4/40). A clinical response was observed in 32 (80%) patients. The 28-day all-cause mortality rate was 7.5% (3/40), while the one-year all-cause mortality rate was 2.5% (1/40). While one patient died owing to severe pancreatitis, no serious adverse events related to tigecycline therapy were reported. However, multiple indices of liver function and pancreatitis precursors increased after treatment with tigecycline compared to before treatment. Conclusion: Tigecycline therapy appears to be well tolerated in renal transplant recipients with multidrug-resistant bacterial infections. Nevertheless, attention should be paid to adverse reactions related to tigecycline therapy, especially gastrointestinal reactions, and the related laboratory tests should be closely monitored.

Risk Factors for Fractures in Renal Transplantation: A Population-Based Cohort Study.

INTRODUCTION: Kidney transplant recipients are at an increased risk of fractures, and targeted preventive strategies are needed. Therefore, in this retrospective cohort study, we investigated a large population-based cohort to identify the transplant recipient-specific risk factors for fractures in Taiwanese kidney transplant recipients. METHODS: We conducted a retrospective cohort study using the National Health Insurance Research Database. Patients who underwent renal transplantation between 2003 and 2015 were identified and followed until December 31, 2015, to observe the development of fractures. Variables associated with the development of post-transplant fractures were identified by calculating hazard ratios in a Cox regression model. RESULTS: 5,309 renal transplant recipients were identified, of whom 553 (10.4%) were diagnosed with post-transplant fractures. Independent predictors of post-transplant fractures included an age at transplant ≥65 years (p < 0.001), female sex (p < 0.001), fractures within 3 years prior to transplantation (p < 0.001), and diabetes mellitus (p < 0.001). In addition, daily prednisolone doses >2.9­5.3 mg/day (p < 0.001), >5.3­8.7 mg/day (p < 0.001), and >8.7 mg/day (p < 0.001) were also independent predictors of post-transplant fractures. Conversely, the use of peritoneal dialysis before renal transplantation (p = 0.021), hypertension (p = 0.005), and the use of tacrolimus (p < 0.001), azathioprine (p = 0.006), mycophenolate mofetil/mycophenolic acid (p = 0.002), mTOR inhibitors (p = 0.004), and calcium supplements (p = 0.009) were inversely correlated with post-transplant fractures. CONCLUSION: We recommend minimizing daily glucocorticoids as early and as far as possible in conjunction with immunosuppressive regimens such as tacrolimus, azathioprine, mycophenolate mofetil/mycophenolic acid, mTOR inhibitors, and calcium supplements, especially in older female recipients and in recipients with diabetes and a history of prior fractures.

Oral Nicotinamide for Actinic Keratosis Prevention in Kidney Transplant Recipients: A Pilot Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: Oral nicotinamide (NAM) has shown promise in preventing actinic keratoses (AKs) in trials based outside of the United States. We assessed the efficacy of oral NAM supplementation in kidney transplant recipients with a history of keratinocyte carcinoma. MATERIAL AND METHODS: Patients enrolled in a 2-week run-in phase, during which NAM 1000 mg was taken twice daily. After a washout period, patients who tolerated the run-in phase were randomized to NAM 500 mg twice daily or placebo. At baseline, 4, 8, and 12 months, dermatologists conducted full-body skin exams to document area-specific AKs. Routine lab work was collected to ensure the stability of renal allograft function. RESULTS: The dosage was reduced from 1000 to 500 mg due to gastrointestinal symptoms in the run-in phase. Patients were randomized to NAM (n = 10) or placebo (n = 11). At 12 months, mean AK count was 30.8 (95% CI -11.7-73.4) for NAM and 26.6 (95% CI 10.8-42.5) for placebo. The difference in percent AK count change at 12 months compared with baseline was 259.8% (95% CI -385.9 to 905.5) for NAM and 72.4% (95% CI -118.6 to 263.5) for placebo. The between-group difference in percent AK change was not significant (P = .38). There was no attrition in the placebo group and 40% attrition in the NAM arm. DISCUSSION: Nicotinamide did not decrease AK development among kidney transplant recipients. Limitations include drug tolerability, small sample size, and single-center trial nature.

Efficacy of iguratimod on mineral and bone disorders after kidney transplantation: a preliminary study.

BACKGROUND: Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs). METHODS: A post hoc analysis was conducted among the subjects in our previous randomized clinical trial (NCT02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CTx), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test. RESULTS: At 52 weeks after enrollment, the iguratimod group had lower osteocalcin (p = 0.010), BALP (p = 0.015), NTx (p = 0.007), CTx (p = 0.012), CAC (p = 0.080) and TAC scores (p = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable. CONCLUSION: Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT.

Association of habitual coffee consumption with obesity, sarcopenia, bone mineral density and cardiovascular risk factors: A two-year follow-up study in kidney transplant recipients.

BACKGROUND & AIMS: Recent evidence suggests that moderate coffee intake is associated with multiple health benefits, including lower risk of obesity, sarcopenia and cardiovascular disease (CVD) in the general population. However, to date, no study has evaluated these associations in kidney transplant recipients (KTR). The aim of the present study was to evaluate the association of habitual coffee consumption with obesity, sarcopenia, bone mineral density and CVD risk factors in KTR. METHODS: This prospective 2 years-follow-up study included 170 KTR (59% men) aged 49.5 (42.0-57.0) years. At baseline participants were submitted to the following evaluations: clinical, laboratorial, dietary intake (including coffee), muscle strength, anthropometric and body composition by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). After two years 163 KTR were re-evaluated by anthropometry, BIA and muscle strength. Sarcopenia was defined according to EWGSOP2. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidemia, metabolic syndrome and hyperhomcysteinemia. Participants were stratified according to coffee intake: 0 or 1 time/day (Gr0-1) and 2 or 3 times/day (Gr2-3). RESULTS: The median coffee consumption was 200 (150-250)mL/day and 112 (71-155)mL/1000 kcal/day. At baseline, Gr2-3 vs. Gr0-1 exhibited significantly higher values of waist circumference, waist-to-height ratio (WHtR) and presented a higher odds ratio for central obesity according to WHtR (2.68; 95%CI:1.19-6.02; p = 0.02) after adjustment for confounders. Coffee consumption (mL/1000 kcal/day) showed, even after adjustment for confounders, (1) a positive association with all parameters of body adiposity (anthropometry, BIA and DXA) and (2) a negative association with muscle quality index. After two years, coffee intake (mL/1000 kcal/day) at baseline presented a positive correlation with changes in fat mass (kg) by BIA (r = 0.22, p = 0.01) after adjustment for confounders. CONCLUSION: This study suggests that in KTR, higher coffee consumption is associated with increased adiposity, specially, central adiposity and lower muscle quality, but is not related with the other evaluated parameters.

Vitamin D supplementation reduced blood inflammatory cytokines expression and improved graft function in kidney transplant recipients.

Background: Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection). Methods: A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant. Results: Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1ß, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1ß, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05). Conclusion: This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs.

[Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data].

BACKGROUND: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

The Impact of Cholecaciferol Supplementation on Bone Mineral Density in Long-Term Kidney Transplant Recipients.

Although reduced bone mineral density (BMD) is associated with a higher risk of fractures, morbidity, and mortality in kidney transplant patients (KTRs), there is no consensus on optimal treatment for the alterations of BMD in this population. This study aims at assessing the effect of cholecalciferol supplementation on BMD over a follow-up period of 2 years in a cohort of long-term KTRs. Patients with age ≥ 18 years were included and divided into two subgroups based on treatment with bisphosphonate and/or calcimimetics and/or active vitamin D sterols (KTRs-treated) or never treated with the above medications (KTRs-free). BMD was evaluated at lumbar vertebral bodies (LV) and right femoral neck (FN) with standard DEXA at the beginning and end of the study. According to World Health Organization (WHO) criteria, results were expressed as T-score and Z-score. Osteoporosis and osteopenia were defined as T score ≤ -2.5 SD and T score < -1 and >-2.5 SD, respectively. Cholecalciferol was supplemented at a dose of 25,000 IU/week over 12 weeks followed by 1500 IU/day. KTRs-free (n. 69) and KTRs-treated (n. 49) consecutive outpatients entered the study. KTRs-free were younger (p < 0.05), with a lower prevalence of diabetes (p < 0.05) and of osteopenia at FN (46.3 % vs. 61.2 %) compared to KTRs-treated. At the entry none of the study subjects had a sufficient level of cholecalciferol; Z-score and T-score at LV and FN were not different between groups. At the end of the study period, serum cholecalciferol concentration was significantly increased in both groups (p < 0.001); the KTRs-free group presented an improvement in both T-score and Z-score at LV (p < 0.05) as well as a lower prevalence of osteoporotic cases (21.7% vs. 15.9%); in contrast, no changes were recorded in KTR-treated individuals. In conclusion, supplementation with cholecalciferol ameliorated Z-score and T-score at LV in long-term KTRs who had been never treated with active or inactive vitamin D sterols, bisphosphonates, and calcimimetics. Future endeavours are needed to confirm these preliminary findings.

Is Serum Magnesium Level Associated With Serum Lipid Levels in Kidney Transplant Recipients?

BACKGROUND: Magnesium (Mg) is key in diabetes mellitus, hyperlipidemia, and cardiovascular disease. METHODS: This is a retrospective cross-sectional study including 103 kidney transplant recipients. Patients aged under 18 years, patients treated with Mg supplementation, antihyperlipidemic agents, or diuretics, and patients with active infection or malignancy were not enrolled. Patients were divided into 2 groups according to median serum Mg level. The atherogenic index of plasma was calculated by a logarithmic transformation of the number acquired by dividing the molar concentrations of serum triglyceride by high-density lipoprotein value. RESULTS: The mean serum Mg level was 1.91 ± 0.28 mg/dL. Six patients (5.8%) had hypomagnesemia (Mg <1.5 mg/dL), and 2 (1.9%) had hypermagnesemia (Mg >2.6 mg/dL). Serum Mg level was negatively correlated with body mass index, estimated glomerular filtration rate (eGFR), and tacrolimus trough level and positively correlated with levels of phosphorus, total cholesterol, and low-density lipoprotein (LDL-C). There was no correlation between serum Mg and triglyceride, high-density lipoprotein, atherogenic index of plasma, and cyclosporin A trough level. Patients with Mg >1.87 mg/dL had lower eGFR, tacrolimus, and cyclosporin A trough level and higher total cholesterol and LDL-C compared to those with Mg ≤1.87 mg/dL. In adjusted ordinal analysis, eGFR (hazard ratio (HR): 0.981, 95% CI 0.964-0.999, P = .036) and total cholesterol (HR: 1.015, 95% CI 1.004-1.027, P = .008) were independently associated with serum Mg. In multivariate linear regression analysis, serum Mg level was independently associated with LDL-C (ß = .296, t = 3.079, P = .003) and total cholesterol (ß = .295, t = 3.075, P = .003). CONCLUSION: Serum Mg level may have an important impact on dyslipidemia in kidney transplant recipients.

Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients.

BACKGROUND: Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. METHODS: In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) µg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized ß 0.49, P < .001). CONCLUSIONS: Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.

A Case of Hypokalemia Caused by Left Native Renal Artery Stenosis in a Kidney Transplant Recipient.

A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor kidney transplantation from her husband. After the kidney transplantation, her serum creatinine level remained around 0.7 mg/dL, but her serum potassium level remained low at around 3.5 mEq/L despite potassium supplementation and spironolactone. The patient's plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly elevated (20 ng/mL/h and 868 pg/mL, respectively). A CT angiogram of the abdomen performed 1 year previously suggested stenosis of the left native renal artery, which was considered responsible for the hypokalemia. Renal venous sampling was done on both the native kidneys and the transplanted kidney. Since renin secretion from the left native kidney was significantly elevated, a laparoscopic left nephrectomy was performed. Postoperatively, the renin-angiotensin-aldosterone system was markedly improved (PRA: 6.4 ng/mL/h, PAC: 147.3 pg/mL), and the serum potassium levels also improved. Pathological examination of the removed kidney showed many atubular glomeruli and hyperplasia of the juxtaglomerular apparatus (JGA) in residual glomeruli. In addition, renin staining showed strong positivity in the JGA of these glomeruli. Here, we report a case of hypokalemia caused by left native renal artery stenosis in a kidney transplant recipient. This valuable case study provides histological confirmation of maintained renin secretion in an abandoned native kidney after kidney transplantation.

The Effect of the Gut Microbiota on Transplanted Kidney Function.

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.

Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: Results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial.

Vitamin D sufficiency is associated with a reduced risk of fractures, diabetes mellitus, cardiovascular events, and cancers, which are frequent complications after renal transplantation. The VITALE (VITamin D supplementation in renAL transplant recipients) study is a multicenter double-blind randomized trial, including nondiabetic adult renal transplant recipients with serum 25-hydroxy vitamin D (25(OH) vitamin D) levels of <30 ng/mL, which is randomized 12 to 48 months after transplantation to receive high (100 000 IU) or low doses (12 000 IU) of cholecalciferol every 2 weeks for 2 months and then monthly for 22 months. The primary outcome was a composite endpoint, including diabetes mellitus, major cardiovascular events, cancer, and death. Of 536 inclusions (50.8 [13.7] years, 335 men), 269 and 267 inclusions were in the high-dose and low-dose groups, respectively. The serum 25(OH) vitamin D levels increased by 23 versus 6 ng/mL in the high-dose and low-dose groups, respectively (P < .0001). In the intent-to-treat analysis, 15% versus 16% of the patients in the high-dose and low-dose groups, respectively, experienced a first event of the composite endpoint (hazard ratio, 0.94 [0.60-1.48]; P = .78), whereas 1% and 4% of patients in the high-dose and low-dose groups, respectively, experienced an incident symptomatic fracture (odds ratio, 0.24 [0.07-0.86], P = .03). The incidence of adverse events was similar between the groups. After renal transplantation, high doses of cholecalciferol are safe but do not reduce extraskeletal complications (trial registration: ClinicalTrials.gov; identifier: NCT01431430).

Effect of vitamin K supplementation on serum calcification propensity and arterial stiffness in vitamin K-deficient kidney transplant recipients: A double-blind, randomized, placebo-controlled clinical trial.

Vitamin K deficiency is common among kidney transplant recipients (KTRs) and likely contributes to progressive vascular calcification and stiffness. In this single-center, randomized, double-blind, placebo-controlled trial, we aimed to investigate the effects of vitamin K supplementation on the primary end point, serum calcification propensity (calciprotein particle maturation time, T50), and secondary end points arterial stiffness (pulse wave velocity [PWV]) and vitamin K status in 40 vitamin K-deficient KTRs (plasma dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP] ≥500 pmol/L). Participants (35% female; age, 57 ± 13 years) were randomized 1:1 to vitamin K2 (menaquinone-7, 360 µg/day) or placebo for 12 weeks. Vitamin K supplementation had no effect on calcification propensity (change in T50 vs baseline +2.3 ± 27.4 minutes) compared with placebo (+0.8 ± 34.4 minutes; Pbetween group = .88) but prevented progression of PWV (change vs baseline -0.06 ± 0.26 m/s) compared with placebo (+0.27 ± 0.43 m/s; Pbetween group = .010). Vitamin K supplementation strongly improved vitamin K status (change in dp-ucMGP vs baseline -385 [-631 to -269] pmol/L) compared with placebo (+39 [-188 to +183] pmol/L; Pbetween group < .001), although most patients remained vitamin K-deficient. In conclusion, vitamin K supplementation did not alter serum calcification propensity but prevented progression of arterial stiffness, suggesting that vitamin K has vascular effects independent of calciprotein particles. These results set the stage for longer-term intervention studies with vitamin K supplementation in KTRs. TRIAL REGISTRY: EU Clinical Trials Register (EudraCT Number: 2019-004906-88) and the Dutch Trial Register (NTR number: NL7687).

Risk Factors of New-onset Diabetes After Renal Transplantation and Prognostic Analysis.

Context: New-onset diabetes after transplantation (NODAT) is one of the most common complications after renal transplantation and in kidney-transplant recipients is closely related to long-term adverse outcomes for recipients and transplants. The risk factors for NODAT still require exploration. Objectives: The study intended to explore the risk factors for new-onset diabetes after transplantation (NODAT) for patients receiving a renal transplantation, to provide a theoretical basis for reducing the incidence rate of NODAT and promoting a better outcome for patients. Design: The research team designed a retrospective study using clinical data of patients receiving renal transplantation at a hospital. Setting: The study took place in the Department of Urology at Xuanwu Hospital at Capital Medical University in Beijing, China. Participants: Participants were 396 patients who had undergone renal transplantation at the hospital, of whom 28 had NODAT syndrome, the NODAT group, and 368 didn't meet the diagnostic criteria for NODAT, the N-NODAT group. Outcome Measures: The research team calculated the incidence rate of NODAT and determined the causes of the disease, evaluated participants' preoperative risk factors-gender, preoperative systolic blood pressure (SBP), preoperative diastolic blood pressure (DBP), height, family history of diabetes, weight, smoking habits, age, drinking habits, pretransplant body mass index (BMI), preoperative fasting blood glucose, triglycerides (TG), total cholesterol (TC)-and their postoperative risk factors-acute rejection, use of immunosuppressive agents, blood CsA concentration, blood FK506 concentration, and renal function. Additionally, the team subjected the data in the two groups to univariate, logistic regression analysis and to multivariate, unconditional, logistic regression analysis to discover risk factors for NODAT. Results: Among the 396 participants, 28 had NODAT (7.1%), and 368 didn't suffer NODAT (92.9%). Statistically significant differences existed between the groups in participants' ages (0.013), weights (P = .032), smoking habits (P = .034), drinking habits (P = .034), BMIs (P = .023), preoperative fasting blood glucose (P < .05), preoperative TG (P < .05), and preoperative TC (P < .01). In the univariate logistic regression analysis, significant associations existed between age (P = .016), weight (P = .033), BMI (P = .025), smoking habits (P = .035), drinking habits (P = .043), preoperative fasting blood glucose (P = .048), preoperative TG (P = .049), preoperative TC (P = .009), acute rejection (P = .009), and immunosuppressive agents (P = .012) and the occurrence of NODAT (P < .05). In the multivariate unconditional logistic stepwise regression analysis, acute rejection (P = .011) and use of FK506 in immunotherapy (P = .013) were independent risk factors for NODAT. Conclusions: The risk factors of NODAT include age, weight, BMI, smoking habits, drinking habits, preoperative fasting blood glucose, preoperative TG, preoperative TC, acute rejection and exposure to immunosuppressive agents. Among them, only acute rejection and immunosuppressive agents are modifiable factors. The application of CsA as an immunosuppressive agent after surgery may decrease the incidence rate of NODAT and prolong the longevity of patients receiving renal transplantation.

Anemia after kidney transplantation.

Anemia is a frequent complication in pediatric kidney transplant recipients (KTR) with a variable reported prevalence estimated between 20 and 80% depending on how defined. Causes of and risk factors for post-transplantation anemia (PTA) are multifactorial with iron deficiency being the primary cause of early PTA (within the first 6 months after transplantation) and impaired glomerular filtration rate (GFR) commonly responsible for late PTA (after 6 months). Medications, viral infections, chronic inflammation, and comorbidities also play a role. PTA has relevant long-term consequences and is a potential risk factor for allograft dysfunction, cardiovascular morbidity, and mortality. Thus, an anemia evaluation, approximately 3 months post-transplantation, is recommended in order to start early treatment and improve prognosis. Iron status, vitamin B12, folate, markers of hemolysis, and viral PCR should be checked, and medications, in particular combinations of medications, should be carefully evaluated. PTA treatment may be challenging and should be directed to the underlying causes. Iron supplementation and erythropoietin therapy, not extensively used in KTR, may be indicated. Every effort should be made to avoid blood transfusions in the pre-transplant period to avoid allosensitization. Anemia should be corrected to prepare candidates for kidney transplantation in order to reduce the need for perioperative blood transfusions as well.

Successful treatment of Talaromyces marneffei pneumonia in a HIV-negative renal transplantation recipient: A case report.

RATIONALE: Talaromyces marneffei causes life-threatening opportunistic fungal infections in immunocompromised patients. It often has a poorer prognosis in non-human immunodeficiency virus (HIV)-infected than in HIV-infected individuals because of delayed diagnosis and improper treatment. PATIENT CONCERNS: A 51-year-old man presented with complaints of pyrexia, cough, and expectoration that had lasted for 15 day. This patient has been taking anti-rejection medication since kidney transplant in 2011. DIAGNOSIS: T marneffei pneumonia; post renal transplantation; renal insufficiency; hypertension. INTERVENTIONS: Intravenous moxifloxacin was administered on admission. After the etiology was established, moxifloxacin was discontinued and replaced with voriconazole. The tacrolimus dose was adjusted based on the blood concentration of tacrolimus and voriconazole. OUTCOMES: The patient was successfully treated and followed-up without recurrence for 1 year. LESSONS: A high degree of caution should be maintained for the possibility of T marneffei infection in immunodeficient non-HIV patients who live in or have traveled to T marneffei endemic areas. Early diagnosis and appropriate treatment can prevent progression of T marneffei infection and achieve a cure. Metagenomic next-generation sequencing (mNGS) can aid the physician in reaching an early pathogenic diagnosis. Close monitoring of tacrolimus and voriconazole blood levels during treatment remains a practical approach at this time.

Risk factors for subchondral insufficiency fracture of the femoral head in renal transplant patients.

INTRODUCTION: Risk factors associated with subchondral insufficiency fracture (SIF) of the femoral head have not been established. The aim of the present study was to determine the incidence and risk factors for SIF of the femoral head following renal transplantation (RT). MATERIALS AND METHODS: We analyzed the cases of 681 RT patients (mean age at surgery: 49.5 ± 13.6 years, 249 women, 432 men) to determine the incidence of SIF. Hip magnetic resonance imaging (MRI) was performed 6 months post-RT. The following potential predictors of SIF were evaluated: (1) patient's condition at RT: bone mineral density (BMD), pre-RT laboratory values including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone; the patient and donor's blood relationship; and mismatching number of human leukocyte antigens (HLAs), and (2) post-RT dosage(s) of steroid(s), the immunosuppressive regimen, and the incidence of acute rejection. RESULTS: SIF was observed in 15 hips (13 patients, 1.9%). We successfully matched 39 patients without SIF. A multivariate logistic regression analysis adjusted for cumulative dosages of steroids, revealed the following were risk factors for SIF: osteoporosis (OR: 11.4, p = 0.046), lumbar BMD (OR: 0.003, p = 0.038), pre-RT serum P (OR 2.68, p = 0.004), and pre-RT serum Ca × P (OR: 1.11, p = 0.005). CONCLUSION: Since osteoporosis, the lumbar BMD, serum P, and serum Ca × P were identified as risk factors for a post-RT SIF, these factors should be evaluated before RT for the prediction of the SIF risk.