Associations between transfusion reactions and thromboembolism development in blood-transfused patients: A retrospective cohort study.

BACKGROUND: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. STUDY DESIGNS AND METHODS: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood-transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow-up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between-cohort risk differences, a Kaplan-Meier survival analysis and multiple Cox proportional hazard model was used. RESULTS: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non-TR group. The risk of VTE or PE was twice as high in the TR group than in the non-TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49-4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. CONCLUSION: TRs are associated with increased long-term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow-up.

A new missense mutation of calcium sensing receptor with isoleucine replaced by serine at codon 857 leading to type V Bartter syndrome.

Several genetic defects on thick ascending limb (TAL) of Henle loop were reported to cause Bartter syndrome (BS) characterized by metabolic alkalosis, hypokalemia, and normal or low blood pressure. Among them, defective basolateral calcium sensing receptors (CaSR) on TAL could result in type V BS that not only presents typical characteristics of BS but also hypocalcemia. Herein we report a 54 years old female patient with a novel mutation of CaSR that leads to type V BS. A sequencing of CaSR gene in peripheral blood mononuclear cells and urine stem cells both disclosed a heterozygous substitution of thymine for guanine (NM_001178065.1:c.2570T > G) in exon 7 at codon 857 resulting in substitution of isoleucine for serine (p.I857S). We performed functional tests of the mutant CaSR gene in vitro using urine stem cells to determine whether this mutation is responsible for the clinical presentations. Urine stem cells expressing abundant CaSR on flow cytometry of this patient and a normal subject were obtained for in vitro functional studies, including intracellular calcium and inositol 1,4,5-trisphosphate concentrations in response to increasing concentrations of extracellular calcium. The results show all of their responses to extracellular calcium are extremely sensitive in urine stem cells of the case as compared to those of the normal subject, indicating a prominent gain-of-function mutation. A novel mutation I857S in transmembrane domain 7 of CaSR in our patient would be added to the list of mutations leading to type V BS.

Steroid-induced hypokalemic periodic paralysis: a case report and literature review.

BACKGROUND: Hypokalemic periodic paralysis (HPP) is a rare channelopathy characterized by episodic attacks of acute muscle weakness concomitant with hypokalemia. The etiology of hypokalemia is the shift of potassium into the cells, and the clinical symptoms resolve when potassium starts to leak back to the serum. Most of the time, the underlying ion channel defects are well compensated, and an additional trigger is often required to initiate an attack. Well-known trigger factors include carbohydrate-rich meals, exercise followed by rest, stress, cold weather, and alcohol consumption. CASE PRESENTATION: Here, we present the case of a 26-year-old Asian man who suffered from an acute onset of bilateral lower limb weakness with hypokalemia following dexamethasone injection. He was diagnosed with HPP. CONCLUSIONS: We would like to remind physicians to think of steroids as an unusual precipitating factor while managing patients with HPP, per results of this case study.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and the Risk of Developing Incidental Tuberculosis: A Population-Based Cohort Study.

Background and Objectives: Treatment for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) must deal with immunosuppression, as well as infections associated with a compromised immune system, such as tuberculosis (TB). Our aim was to examine the risk of incidental TB after diagnosis of AAV. Materials and Methods: This retrospective population-based cohort study was based on the data from the National Health Insurance Research Database in Taiwan. Patients with newly diagnosed granulomatous polyangiitis or microscopic polyangiitis were identified between 1 January 2000 and 31 December 2012. The primary outcome was risk of incidental TB. Cox proportional hazard models were used to evaluate the association between AAV and incidental TB. Results: A total of 2257 patients with AAV and a propensity-score matched cohort of 9028 patients were studied. Overall, patients with AAV were at a 1.48× higher risk of contracting incidental TB than the patients in the matched cohort (adjusted HR 1.48; 95% confidence interval [CI], 1.02-2.15). Note that the highest risk of contracting incidental TB was in the first two years following a diagnosis of AAV, with a nearly 1-fold increase in risk (adjusted HR, 1.91; 95% CI, 1.01-3.60). Female AAV patients were 3.24× more likely than females without AAV to develop TB (adjusted HR 3.24; 95% CI, 1.85-5.67). Conclusions: Patients with AAV exhibit a 48% elevated TB risk, notably, a 91% increase within the first two years postdiagnosis. Female AAV patients face a 3.24 times higher TB risk compared to females without AAV. This study is limited by potential misclassification and overestimation of AAV cases. Clinicians should closely monitor TB risk in AAV patients, especially in females and the initial two years following diagnosis.

Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

BACKGROUND: Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. METHODS: We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. RESULTS: Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n = 4), cellulitis/fasciitis (n = 4) and urinary tract infection (UTI) (n = 4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio = 6.1; 95% CI: 1.2-31.9, p = 0.031) and non-remission by treatment (Hazard ratio = 4.4; 95% CI: 1.2-15.6, p = .023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. CONCLUSIONS: Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Aluminum overload in the reverse osmosis dialysis era: does it exist?

BACKGROUND: Aluminum accumulation is a well-described complication in dialysis patients. Improvements in hemodialysis technology have possibly eliminated the occurrence of aluminum overload. Limited evidence suggests that aluminum overload may decline in the era of aluminum removal from dialysis fluids, even with the use of aluminum binders. METHODS: We examined the data from January 2014 to June 1, 2020, identified through our electronic records, to evaluate the desferrioxamine (DFO) test results for aluminum overload. The presentation and treatment of aluminum overload were recorded. RESULTS: Ninety-nine dialysis patients were enrolled for the DFO test. Forty-seven patients (47.5%) were identified as DFO test positive for aluminum overload, of which 14 (14/47) patients had symptoms, including one patient with an unexplained fracture, eight patients with unexplained anemia despite high-dose erythropoiesis-stimulating agents, and five patients with hypercalcemia (serum calcium >11 mg dL-1). None of the patients with aluminum overload developed encephalopathy. Only four of the 47 patients had microcytic anemia. Patients requiring longer treatments (>10 months versus <10 months) had similar basal serum aluminum (p = 0.219) but had an increase in serum aluminum after DFO (p = 0.041). Furthermore, the treatments decreased erythropoietin doses in the aluminum overload group, with serum total alkaline phosphatase levels <60 U L-1 (p = 0.028). CONCLUSION: We concluded that aluminum overload existed in the reverse osmosis dialysis era. In light of non-obvious symptoms, such as anemia and bone turnover change, serum aluminum in dialysis patients should be monitored in countries using aluminum-based phosphate binders, despite reverse osmosis dialysis.

Effect of anti-diabetic drugs in dialysis patients with diabetes: a nationwide retrospective cohort study.

BACKGROUND: Type 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis. METHODS: Using a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011-2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis. RESULTS: A total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05). CONCLUSIONS: For dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.

Incidence and risk factors for chronic kidney disease in patients with congenital heart disease.

BACKGROUNDS: Chronic kidney disease (CKD) is underdiagnosed in children with congenital heart disease (CHD). Our aim was to study the incidence of CKD in CHD children and identify risk factors for CKD. METHODS: CHD patients were enrolled from the Kaohsiung Veterans General Hospital database between 2010 and 2019. Patient age at enrollment was age at first visit to the hospital. The end of follow-up was marked by the last measurement of serum creatinine, urine protein-to-creatinine ratio (UPCR), or urine microalbumin-to-creatinine ratio (UACR) after enrollment, and only patients who underwent the aforementioned tests in 2 different years were included. Patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were diagnosed as having CKD and were further classified into clinically recognized CKD (CR-CKD, defined as eGFR <60 mL/min/1.73m2, UPCR >0.5, or UACR >30 mg/g) and non-clinically recognized CKD (NCR-CKD). Their demographic data, CHD category, heart surgery types, medications, and contrast-related examinations during follow-up were collected. RESULTS: The study included 359 CHD patients, of whom 167 (46.5%) developed CKD (18 patients with CR-CKD and 341 with NCR-CKD). Patients with CR-CKD were significantly older at enrollment than patients with NCR-CKD. Corrective heart surgery may be a protective factor for CKD. Furthermore, cyanotic heart disease, two or more image-related contrast exposures, and diuretic use may be associated with CKD. CONCLUSION: CHD patients have a high incidence of CKD. The early detection of CKD and prompt corrective heart surgery for CHD may be beneficial for kidney function.

Prophylactic hemodialysis following coronary angiography and one-year outcomes in non-dialysis patients with chronic kidney disease: A propensity-matched study.

BACKGROUND/PURPOSE: Prophylactic hemodialysis after coronary angiography in patients with chronic kidney disease (CKD) prevents contrast nephropathy; however, the one-year outcomes are unclear. This study aimed to investigate the one-year outcomes of prophylactic hemodialysis against standard treatment in patients with CKD who underwent coronary angiography. METHODS: A cohort study of 359 patients with CKD, coronary artery disease (CAD), and serum creatinine levels of 176.8-530.4 µmol/L, who were referred for elective coronary angiography was conducted. Propensity score matching identified 118 patient pairs for outcome comparisons. The hemodialysis group underwent prophylactic hemodialysis after coronary angiography, whereas the control group received standard treatment. The study's primary outcome was free from dialysis was considered the primary outcome, whereas the secondary outcome was overall survival. Unadjusted estimates of the probability of free from dialysis and overall survival were computed using Kaplan-Meier survival curves and log-rank tests. Cox proportional-hazards regression models were used in determining the risk factors associated with ESRD and mortality. RESULTS: During a mean 9.3 months follow-up duration, the hemodialysis group had significantly better free from dialysis (85.6% vs. 64.4%; P = 0.002) and overall survival (85.4% vs. 78.5%; P = 0.008) rates than the control group. Cox proportional-hazards regression analyses of the propensity score-matched patients showed that the hemodialysis group had reduced risks for ESRD and mortality (hazard ratios, 0.32 and 0.48, respectively). CONCLUSION: Prophylactic Hemodialysis following coronary angiography was associated with reduced ESRD and mortality risks in CKD patients with CAD, who did not routinely undergo dialysis.

Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages.

We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-ß and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization.

Deficiency of Urokinase Plasminogen Activator May Impair ß Cells Regeneration and Insulin Secretion in Type 2 Diabetes Mellitus.

: Background: The relationship between urokinase-type plasminogen activator (uPA) and the development of type 2 diabetes mellitus (T2DM) was investigated in the study by using mice and cell models, as well as patients with T2DM. METHODS: In mice models, wild-type and uPA knockout (uPA-/-) BALB/c mice were used for induction of T2DM. In cell models, insulin secretion rate and ß cell proliferation were assessed in normal and high glucose after treating uPA siRNA, uPA, or anti-uPA antibody. In our clinical study, patients with T2DM received an oral glucose-tolerance test, and the relationship between uPA and insulin secretion was assessed. RESULTS: Insulin particles and insulin secretion were mildly restored one month after induction in wild-type mice, but not in uPA-/- mice. In cell models, insulin secretion rate and cell proliferation declined in high glucose after uPA silencing either by siRNA or by anti-uPA antibody. After treatment with uPA, ß cell proliferation increased in normal glucose. In clinical study, patients with T2DM and higher uPA levels had better ability of insulin secretion than those with lower uPA levels. CONCLUSION: uPA may play a substantial role in insulin secretion, ß cell regeneration, and progressive development of T2DM. Supplementation of uPA might be a novel approach for prevention and treatment of T2DM in the future.

Diabetic Macular Edema Is Predictive of Renal Failure in Patients With Diabetes Mellitus and Chronic Kidney Disease.

CONTEXT: Chronic hyperglycemia in patients with diabetes mellitus (DM) causes retinal damage and leakage, resulting in vision loss. Although diabetic retinopathy (DR) and diabetic kidney disease (DKD) are usually correlated, the relationship between diabetic macular edema (DME) and DKD remains unknown. OBJECTIVE: To assess whether DME presence can predict renal failure in patients with DM and chronic kidney disease (CKD). METHODS: This retrospective cohort study used data from 120 healthcare organizations in the TriNetX network. Electronic medical records of approximately 90 million patients were reviewed. The study population was classified into DME and non-DME cohorts. Primary and secondary outcomes were new-onset end-stage renal disease (ESRD) and all-cause mortality, respectively. Covariate factors were incorporated to reduce confounding effects. RESULTS: Before matching, the DME cohort used more medication and had poorer renal function and blood sugar control than the non-DME cohort. Subsequently, the 2 groups were well-matched in demographics, socioeconomic status, lifestyle, comorbidities, and medication usage. The DME cohort had a significantly higher risk of ESRD, dialysis, and renal transplantation than the non-DME cohort. Subgroup analyses showed consistent results irrespective of follow-up duration, initial estimated glomerular filtration rate, or glycated hemoglobin levels. Additionally, the DME cohort had a lower risk of all-cause mortality than the non-DME cohort. CONCLUSION: Statistically significant 5-year increased risks of ESRD, dialysis, and renal transplantation were observed in patients with concurrent DME. Therefore, close monitoring and follow-up of the renal function in DM patients with DME are necessary and strongly recommended.

Corrigendum: Urethral discharge as an early manifestation of urinary tract infection in children ≤24 months old.

[This corrects the article DOI: 10.3389/fped.2023.1149218.].

Urethral discharge as an early manifestation of urinary tract infection in children ≤24 months old.

Background: Children with febrile urinary tract infections (UTIs) are prone to kidney scarring if they are not treated promptly; however, ambiguous symptoms before fever onset makes the early detection of UTIs difficult. Our study aimed to identify urethral discharge as an early manifestation in children with UTI. Methods: This study enrolled 678 children younger than 24 months with paired urinalysis and culture performed between 2015 and 2021; 544 children were diagnosed with UTIs. Clinical symptoms, urinalysis, and paired urine culture results were compared. Results: Urethral discharge was observed in 5.1% of children with UTI and yielded a specificity of 92.5% for diagnosing UTI. Children with urethral discharge had a less severe UTI course, furthermore, nine of them received antibiotics before fever occurred and seven of them were free of fever during UTI course. Urethral discharge was associated with alkalotic urine and Klebsiella pneumonia infection. Conclusions: Urethral discharge is an early symptom in children with UTI; it may present before fever onset and help ensure prompt antibiotic intervention.

Trends in the incidence of urothelial carcinoma in Taiwan after the ban on aristolochic acid-containing Chinese herbal preparations, 2001-2018: a national population-based cohort study.

PURPOSE: Urothelial carcinoma (UC) of the bladder (BUC) and the upper urinary tract (UTUC) are the two most common UCs. The incidence of UTUC in Taiwan is the highest worldwide. Aristolochic acid (AA) was identified as the main cause of UTUC in Taiwan. To explore trends in the incidence of UC in Taiwan after the ban on Chinese herbal preparations containing AA in 2003. METHODS: We used data from the Taiwanese National Health Insurance Research Database-linked Taiwanese National Cancer Registry for 2001-2018. UC was defined in accordance with the International Classification of Disease for Oncology. The age-standardized incidence was calculated on the basis of the World Health Organization standard population. Trends in the incidence were calculated as the annual percent change (APC) by using the Joinpoint regression program. RESULTS: Over the investigated period, the incidence of UC decreased at an average annual percent change (AAPC) of - 1.19% (95% CI - 1.47 ~ - 0.91, P < 0.001). However, the incidence in UTUC significantly increased, with the AAPC being 1.47% (95% CI 1.03 ~ 1.90, P < 0.001). In contrast, the incidence of BUC significantly decreased, with the overall AAPC being - 1.92% (95% CI - 2.3 ~ - 1.54, P < 0. 001). From 2001 to 2018, the overall incidence of UCs and BUC decreased in Taiwan, but the incidence of UTUC significantly increased. CONCLUSION: We suggest to apply the same review standards of new drug development process to herbal preparations and incorporate them into the adverse drug reaction or poison surveillance system. Most importantly, raise public awareness of the potential toxicity of phytotherapy.

Intravitreal Vascular Endothelial Growth Factor Inhibitor Use and Renal Function Decline in Patients with Diabetic Retinopathy.

Adverse renal effects of systemic vascular endothelial growth factor (VEGF) inhibitor treatment are well documented. We aimed to identify associations between intravitreal VEGF inhibitor use and renal function decline in patients with diabetic retinopathy. We included 625 patients with diabetic retinopathy for regular renal function follow-ups and grouped them according to intravitreal therapy (67 with and 558 without treatment). We used a generalized estimating equation model to identify renal function decline risk factors. Increased age (p = 0.02), insulin use (p = 0.01), hypertension (p < 0.01), and ischemic heart disease (p < 0.01) were associated with significantly decreased estimated glomerular filtration rates (eGFRs) in patients with diabetic retinopathy after 1-year follow-up. Compared to the control group, patients who received intravitreal VEGF inhibitor injections showed a declining eGFR trend in the repeated measurement model without statistical significance (p = 0.06). In subgroup analysis, patients with initial eGFR ≤ 30 mL/min/1.73 m2 who received intravitreal VEGF inhibitors had significantly decreased renal function (p < 0.01) compared to those without treatment. Intravitreal VEGF inhibitor injection was associated with renal function deterioration among patients with diabetic retinopathy and advanced chronic kidney disease. Strategies to monitor renal function after treatment should be considered in these high-risk populations.

Kidney bioengineering by using decellularized kidney scaffold and renal progenitor cells.

Patients with end-stage renal disease often need dialysis to maintain their lives because of donor organ shortage. The creation of a transplantable graft to permanently replace kidney function would overcome the organ shortage problem and the morbidity associated with immunosuppression. In the present study, we decellularized rat kidneys by the perfusion of detergent, yielding acellular scaffolds with the vascular, uretic, as well as cortical and medullary architecture. To regenerate the functional organ, we seeded tubular epithelial cells and mouse kidney progenitor cells from the ureter together with endothelial cells and mouse kidney progenitor cells from the renal artery. The renal constructs from seeded cells were cultured in a whole-organ bioreactor. After 3 months of organ culture, the seeded cells formed renal tubules, grew in the glomeruli, and some mouse kidney progenitor cells were also scattered in the interstitium. We tested the function of the bioengineered kidney with standardized perfusate in vitro. The bioengineered kidney not only produced urine but also reabsorbed albumin, glucose, and calcium. We conclude that seeded cell-based bioengineering of kidneys with physiological secreting and reabsorbing properties is possible and holds therapeutic promise.

Erythropoiesis-stimulating agents and incident malignancy in chronic kidney and end-stage renal disease: A population-based study.

Research investigating incident malignancy risk in erythropoiesis-stimulating agent (ESA) users with chronic kidney disease (CKD) is lacking. We aimed to compare the incident cancer risk between ESA and non-ESA users with CKD or end-stage renal disease (ESRD). In this retrospective cohort study, all adults newly diagnosed with CKD or ESRD between 2000 and 2012 were enrolled. The study population included 98,748 patients. After case-control matching, 7115 patients were included. The defined daily dose (DDD) of ESA was used as the unit for measuring the amount of ESA prescribed. The primary outcome was the risk of incident malignancy. The secondary outcomes were incident malignancy risk in different tertiles of cumulative ESA doses and the risk of different types of cancers. The risk of incident malignancy was 1.84 times higher with ESA treatment than without ESA treatment (hazard ratio, 1.84; 95% confidence interval, 1.43-2.36; p < 0.001). The malignancy risk was positively correlated with the cumulative dose of ESA (p-for-trend = 0.001) and a significant difference in the high annual cumulative DDD cohort (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.76-3.25; p < 0.001). The risk of genitourinary malignancy was 12.55 times higher with ESA treatment than without ESA treatment (HR, 12.55; 95% CI, 5.78-27.24; p < 0.001). ESA usage is associated with an increased risk of malignancy, particularly genitourinary cancers, in patients with CKD or ESRD. Clinicians should be aware of the occurrence of malignancy, and keep ESA dosage as low as possible.

Systematic Review of Nutrition Supplements in Chronic Kidney Diseases: A GRADE Approach.

Chronic kidney disease (CKD) is cumulative worldwide and an increasing public health issue. Aside from the widely known protein restriction and medical therapy, less evident is the renal protection of nutrition supplements in CKD patients. This systematic review (SR), using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, aims to summarize and quantify evidence about the prevention effects of vitamin D and analogues, omega-3 polyunsaturated fatty acid (omega-3 PUFA), dietary fiber, coenzyme Q10 (CoQ10), and biotics on CKD progression. This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to examine SRs and/or meta-analysis of clinical controlled trials identified from PubMed, Embase, and the Cochrane Library. Finally, seventeen SRs were included in the qualitative analysis. The beneficial effects of these nutrition supplements in CKD patients mostly seem to be at low to very low evidence on proteinuria, kidney function, and inflammations and did not appear to improve CKD prognosis. The recommendation of nutrition supplements in CKD patients needs to discuss with physicians and consider the benefits over the adverse effects. Longer follow-up of larger randomized trials is necessary to clarify the benefits of nutrition supplements in CKD patients.

Sugar- and artificially-sweetened beverages and the risks of chronic kidney disease: a systematic review and dose-response meta-analysis.

BACKGROUND: Consumption of sugar or artificially-sweetened beverages (SASBs) has been linked to albuminuria, decline in kidney function, and risk of chronic kidney disease (CKD). However, the results are controversial. We therefore aim to evaluate the effects of sugar or artificially-sweetened beverage consumption on CKD risk. METHODS: Original observational studies reporting relative risks (RRs) with 95% confidence intervals (CIs) for the association between sugar or artificially-sweetened beverage consumption and impaired renal function or CKD risk in adults were identified using a systematic search of PubMed and EMBASE from inception to 20 February, 2019. Random effects model was applied to derive summary RRs and 95% CIs. Linear and non-linear dose-response relationships were estimated using data from sugar or artificially-sweetened beverage consumption categories in each study. RESULTS: The summary RR of CKD for high versus low sugar-sweetened beverage consumption was 1.30 (95% CI 0.88-1.94) according to six included studies with a total of 25,455 participants, while the pooled RR of CKD for high versus low artificially sweetened beverage consumption was 1.40 (95% CI 0.65-3.02) according to three studies with a total of 19,995 participants. For dose-response analysis, a significant, increased risk of CKD was observed with the sugar or artificially-sweetened beverage consumption above seven servings per week (P < 0.001). CONCLUSION: Our study found a positive association between consumption of sugar or artificially-sweetened beverage consumption and CKD, though it did not reach statistical significance. However, the dose-response results suggest that more than seven servings per week should be avoided.