Longitudinal causal effect of modified creatinine index on all-cause mortality in patients with end-stage renal disease: Accounting for time-varying confounders using G-estimation.

BACKGROUND: Standard regression modeling may cause biased effect estimates in the presence of time-varying confounders affected by prior exposure. This study aimed to quantify the relationship between declining in modified creatinine index (MCI), as a surrogate marker of lean body mass, and mortality among end stage renal disease (ESRD) patients using G-estimation accounting appropriately for time-varying confounders. METHODS: A retrospective cohort of all registered ESRD patients (n = 553) was constructed over 8 years from 2011 to 2019, from 3 hemodialysis centers at Kerman, southeast of Iran. According to changes in MCI, patients were dichotomized to either the decline group or no-decline group. Subsequently the effect of interest was estimated using G-estimation and compared with accelerated failure time (AFT) Weibull models using two modelling strategies. RESULTS: Standard models demonstrated survival time ratios of 0.91 (95% confidence interval [95% CI]: 0.64 to 1.28) and 0.84 (95% CI: 0.58 to 1.23) in patients in the decline MCI group compared to those in no-decline MCI group. This effect was demonstrated to be 0.57 (-95% CI: 0.21 to 0.81) using G-estimation. CONCLUSION: Declining in MCI increases mortality in patients with ESRD using G-estimation, while the AFT standard models yield biased effect estimate toward the null.

The effects of curcumin-containing supplementations on inflammatory markers and lipid profiles in patients with chronic kidney diseases: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: An evaluation the effects of curcumin on inflammatory markers and lipid profiles among patients with chronic kidney diseases (CKD). METHODS: The electronic databases such as PubMed, and Scopus were searched systematically up until 12 December 2021. To evaluate the quality of the included studies, the Cochrane risk-of-bias tool for randomized trials was utilized. Likewise, data pooling was performed using a random effects model, also called a variance components model. Also, the findings were calculated as weighted mean difference (WMD) with a 95% confidence interval (CI). RESULTS: In the end, this meta-analysis comprised a total number of nine studies. Curcumin intake significantly reduced total cholesterol (TC) (WMD=-13.77 mg/dL; 95% CI, -26.77, -0.77; p=0.04) and tumor necrosis factor alpha (TNF-α) (WMD=-18.87 pg/mL; 95% CI, -28.36, -9.38; p<0.001) compared with controls. The results did not confirm the significant effect of curcumin intake on triglyceride (TG) (WMD=-6.37 mg/dL; 95% CI, -26.59, 13.85; p=0.54), low-density lipoproteins (LDL-C) (WMD=-5.65 mg/dL; 95% CI, -20.81, 9.50; p=0.46), high-density lipoprotein (HDL-C) (WMD=0.16 mg/dL; 95% CI, -2.55, 2.88; p=0.91), and C-reactive protein (CRP) (WMD=-0.13 mg/L; 95% CI, -3.25, 3.30; p=0.93). CONCLUSIONS: Our study showed that curcumin significantly impacts TC and TNF levels in CKD patients.

Longitudinal Causal Effects of Normalized Protein Catabolic Rate on All-Cause Mortality in Patients With End-Stage Renal Disease: Adjusting for Time-Varying Confounders Using the G-Estimation Method.

In this study, we aimed to estimate the causal effect of normalized protein catabolic rate (nPCR) on mortality among end-stage renal disease (ESRD) patients in the presence of time-varying confounding affected by prior exposure using g-estimation. Information about 553 ESRD patients was retrospectively collected over an 8-year period (2011-2019) from hemodialysis facilities in Kerman, Iran. nPCR was dichotomized as <1.2 g/kg/day versus ≥1.2 g/kg/day. Then a standard time-varying accelerated failure time (AFT) Weibull model was built, and results were compared with those generated by g-estimation. After appropriate adjustment for time-varying confounders, weighted g-estimation yielded 78% shorter survival time (95% confidence interval (95% CI): -81, -73) among patients with a continuous nPCR <1.2 g/kg/day than among those who had nPCR ≥1.2 g/kg/day during follow-up, though it was 18% (95% CI: -57, 54) in the Weibull model. Moreover, hazard ratio estimates of 4.56 (95% CI: 3.69, 5.37) and 1.20 (95% CI: 0.66, 2.17) were obtained via weighted g-estimation and the Weibull model, respectively. G-estimation indicated that inadequate dietary protein intake characterized by nPCR increases all-cause mortality among ESRD patients, but the Weibull model provided an effect estimate that was substantially biased toward the null.

Vitamin D Levels After Kidney Transplantation and the Risk of Cytomegalovirus Infection.

BACKGROUND: Some studies reported an association between low levels of vitamin D and the risk of infections, especially viral infections. Kidney transplant patients are at risk of opportunistic infections; however, no study has been conducted on the association between vitamin D levels and the risk of CMV infection. OBJECTIVES: The aim of this study was to compare the level of vitamin D in two groups of patients with and without CMV infection within four months after the transplantation. Moreover, we aimed to find a relation between vitamin D level, before and after transplantation in each group. PATIENTS AND METHODS: This prospective cohort study was conducted in Baqiyatallah hospital in Tehran in 2013. A total of 82 kidney transplant patients were enrolled and vitamin D levels were measured in them before transplantation. The kidney transplant patients had been followed up for four months and monitored for the presence of cytomegalovirus antigen (CMV Ag) in their blood. In patients with positive CMV Ag, vitamin D level was measured again when they became positive but in other patients it was measured at the end of follow-up; at the end, characteristics of patients and vitamin D levels were compared between the two groups. RESULTS: Of all, 40 patients were CMV Ag positive and 42 patients were negative. In most patients transplanted organs were taken from cadaver (66%) and the most common type of dialysis was hemodialysis (92%). Most participants did not undergo antithymocyte globulin therapy (69%) and pulse corticosteroid therapy (83%). Vitamin D level before transplantation was 17.2 ± 11.6 ng/mL. In patients with positive results or at the end of follow-up in patients without CMV Ag, vitamin D level was 16.3 ± 11.4 ng/mL. Only 11% of kidney transplant patients, within four months after transplantation, had a normal level of vitamin D (> 30 ng/mL). There was no significant difference between the two groups for patients' characteristics (P > 0.05). Vitamin D levels, before transplantation and at the time of detecting CMV Ag or at the end of follow-up period in patients without CMV, were not significantly different between the two groups (P > 0.05). However, vitamin D levels decreased in patients with CMV, while it increased in CMV Ag negative patients, which was statistically significant (P = 0.037). CONCLUSIONS: Only 11% of kidney transplant patients, even with a successful transplantation of the kidney and with an acceptable performance of the transplanted kidney, had an adequate level of vitamin D. Although, we did not find any significant association between vitamin D levels and CMV infection during a 4-month follow-up after kidney transplantation. It was observed that, compared with the time before transplantation, vitamin D levels decreased in patients with CMV, while it increased in CMV negative patients.

Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation.

BACKGROUND: Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA) alleles and cytomegalovirus infection (CMV), in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. OBJECTIVES: This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. PATIENTS AND METHODS: This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients' blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. RESULTS: Of all participants, 104 patients (52%) were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient's characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001). Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024); on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020). There was no significant relationship between CMV infection and other HLA alleles. Results of multivariate logistic regression analysis showed that deceased donor renal transplantation (OR = 3.018, 95%CI: 1.662 - 5.480, P < 0.001), presence of HLA-B44 (OR = 4.764, 95%CI: 1.259 - 18.032, P = 0.022) and lack of HLA-B8 (OR = 3.246, 95%CI: 1.030 - 10.230, P = 0.044) were the independent risk factors for developing CMV infection, after kidney transplantation. CONCLUSIONS: The findings of this study showed that deceased donor renal transplantation and the presence of HLA-B44 can make the kidney recipient susceptible to CMV infection after kidney transplantation; on the other hand, the presence of HLA-B8 can have a protective effect.

Chemokine receptor 2-V64I and chemokine receptor 5-Delta32 polymorphisms and clinical risk factors of delayed graft function and acute rejection in kidney transplantation.

INTRODUCTION: Chemokines and chemokine receptors have a pivotal role in immunity and inflammation. We aimed to evaluate their role in kidney transplant rejection. MATERIALS AND METHODS: The association of chemokine (C-C motif) receptor 2 (CCR2)-V64I and CCR5-Delta32 gene polymorphisms with acute rejection (AR) and delayed graft function (DGF) were examined in 100 donor-recipient pairs. The CCR2-V64I and CCR5-Delta32 alleles were determined using polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism, respectively. RESULTS: No associations were found between donors or recipients' CCR2-V64I and CCR5-Delta32 gene polymorphisms and AR or DGF. Of the characteristics of the donors, recipients, and transplantation, glomerulonephritis as a cause of kidney failure in the recipients was weakly associated with AR (relative risk, 6.1; 95% confidence interval, 0.8 to 46.0; P = .07). Transplantation of kidney from females to males was weakly associated with DGF (relative risk, 5.5; 95% confidence interval, 0.9 to 33.0; P = .06). There was a significant association between AR, but not DGF, and graft loss in the patients (relative risk, 28.6; 95% confidence interval, 1.7 to 487.0; P = .03). CONCLUSIONS: Our study failed to suggest CCR2-V64I or CCR5-Delta32 gene polymorphisms as risk factors for AR and DGF in kidney transplantation. Sex-matching between donors and recipients should be considered for living donor kidney transplantation.