Acute kidney injury associated with anti-PD-1 and anti-PD-L1 drugs: a meta-analysis of randomized clinical trials.

BACKGROUND: Immune Checkpoint Inhibitors (ICI) have been widely used in treating different types of cancer. They increase survival in many oncologic patients and enable cancer-specific therapy. Acute Kidney Injury (AKI) is one of the adverse effects associated with using ICI, where knowledge of the prevalence and renal histological findings are still reasons for discussion. OBJECTIVE: Therefore, this meta-analysis evaluates the association between ICI use and AKI. METHODS: The search was performed in PubMed, Lilacs, and Cochrane platforms. Studies published up to December 1, 2022, were included. RESULTS: A total of 16 studies met the established PICOT criteria and were included in this review. Comparing the ICI plus chemotherapy against chemotherapy alone, the relative risk (RR) for AKI's development with ICI use was 2.89 (95%CI 1.37-6.10). In the analyses by class and drug type, programmed cell death 1 monoclonal antibody (anti-PD-1) showed an increased risk of 2.11 (95%CI 1.26-3.52), and pembrolizumab demonstrated a risk of AKI (RR= 2.77, 95%CI 1.46-5.26). Likewise, regarding the severity of AKI, AKI grade 3 or higher was more common in the ICI plus chemotherapy compared to the chemotherapy group: 3.66 (95%CI 1.19-11.30), while the subgroup analyses pooled studies comparing ICI alone versus chemotherapy alone in the control group did not demonstrate an association with AKI. CONCLUSIONS: These findings suggest that ICI use is associated with an increased risk of AKI and that anti-PD-1 use is associated with a higher incidence of renal adverse events than programmed cell death ligand 1 monoclonal antibody (anti-PD-L1). Studies with adequate power and well-defined criteria for acute interstitial nephritis, nowadays taken as a synonym for AKI related to ICI, are necessary.

Analysis of cerebral blood flow and intracranial hypertension in critical patients with non-hepatic hyperammonemia.

Hyperammonemia in adults is generally associated with cerebral edema, decreased cerebral metabolism, and increased cerebral blood flow. The aim of this study was to evaluate the association between non-hepatic hyperammonemia and intracranial hypertension assessed by Doppler flowmetry and measurement of the optic nerve sheath. A prospective cohort study in critically ill patients hospitalized in intensive care units of a University Hospital between March 2015 and February 2016. Clinical data and severity scores were collected and the Glasgow coma scale was recorded. Serial serum ammonia dosages were performed in all study patients. Transcranial Doppler evaluation was carried out for the first 50 consecutive results of each stratum of ammonemia: normal (<35 µmol/L), mild hyperammonemia (≥35 µmol/L and < 50 µmol/L), moderate hyperammonemia (≥50 µmol/L and < 100 µmol/L), and severe hyperammonemia (≥100 µmol/L). The measurement of the optic nerve sheath was performed at the same time as the Doppler examination if the patient scored less than 8 on the Glasgow coma scale. There was no difference in flow velocity in the cerebral arteries between patients with and without hyperammonemia. Patients with hyperammonemia presented longer ICU stay. Optic nerve sheath thickness was higher in the group with severe hyperammonemia and this group presented an association with intracranial hypertension. Higher mortality was observed in the severe hyperammonemia group. There was an association between severe hyperammonemia and signs of intracranial hypertension. No correlation was found between ammonia levels and cerebral blood flow velocity through the Doppler examination.

Is hemodiafiltration superior to high-flow hemodialysis in reducing all-cause and cardiovascular mortality in kidney failure patients? A meta-analysis of randomized controlled trials.

INTRODUCTION: Hemodiafiltration (HDF) and high-flux hemodialysis (hf-HD) are different methods of kidney replacement therapy (KRT) used for the treatment of kidney failure patients. A debate has raged over the last decade about the survival benefit of patients with the use of HDF compared with hf-HD, but with divergent results from randomized controlled trials. Therefore, this study aimed to perform a meta-analysis to compare HDF and hf-HD regarding all-cause and cardiovascular mortality. METHODS: PubMed and Cochrane databases were searched until July 19, 2023, for randomized clinical trials comparing HDF and hf-HD in patients on maintenance dialysis. A meta-analysis was performed using Stata 16.1, applying fixed or random effect models according to the heterogeneity between studies. FINDINGS: Of the 496 studies found, five met the inclusion criteria. Compared with the hf-HD group, the risk ratio (RR) for all-cause mortality with HDF use was 0.76 (95% CI: 0.67-0.88, I2 = 0%). HDF was associated with lower cardiovascular mortality, although the sensitivity analysis showed that the result differed between scenarios. Subgroup analysis showed lower all-cause mortality among patients without diabetes in the HDF group compared with hf-HD (RR 0.66, 95% CI: 0.51-0.81, I2 = 0%), but not in diabetic patients (RR = 0.89, 95% CI: 0.65-1.12, I2 = 0.0%). A subgroup analysis considering convection volumes was not performed, but the studies with the highest weight in the meta-analysis described convection volume as more than 20 L/session. DISCUSSION: More clinical studies considering critical risk factors, such as advanced age and preexisting cardiovascular disease, are needed to confirm the supremacy of HDF over hf-HD on the survival of patients treated by these two forms of kidney replacement therapy.

Acute kidney injury is associated with soluble vascular cell adhesion molecule 1 levels and short-term mortality in patients with ischemic stroke.

BACKGROUND: The mechanisms that modulate the onset of acute kidney inlury (AKI) after ischemic stroke (IS) and valuable biomarkers to predict the occurrence and prognosis of AKI among patients with IS are missing. OBJECTIVE: To evaluate the frequency of AKI and the prognostic validity of clinical and laboratory biomarkers in predicting AKI and short-term mortality after the IS. METHODS: Ninety-five patients with IS were enrolled. Baseline IS severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and disability was determined after three-month follow-up using the modified Rankin Scale. Patients with IS were also categorized as survivors and non-survivors after the follow-up. Baseline data and laboratory biomarkers were obtained up to 24 h of the admission. RESULTS: Fifteen (15.7 %) patients with IS presented AKI. The proportion of patients with vitamin D deficiency and the mortality were higher among those with AKI than those without AKI (p=0.011 and p-0.009, respectively). Patients with AKI showed higher disability and higher increased soluble vascular cellular adhesion molecule-1 (sVCAM-1) than those without AKI (p=0.029 and p=0.023, respectively). Logistic regression analysis showed that only sVCAM-1 was associated with the occurrence of AKI after IS [odds ratio (OR): 2.715, 95 % confidence intereval (CI): 1.12-6.67, p=0.027]. When both AKI and NIHSS were evaluated as explanatory variables, this panel showed an OR of 5.782 (95 % CI: 1.09-30.43, p<0.001) and correctly classified 83.6 % of cases. CONCLUSION: In conclusion, sVCAM-1 levels showed a potential useful for prediction of AKI after IS.

Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case-control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials.

INTRODUCTION: Hyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients. METHODS: PubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model. RESULTS: Among 567 studies found, eighteen met the inclusion criteria (n=2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02ml/min/1.73m2 (95%CI 0.41 to 3.63, P=0.014) and -0.19mg/dl (95%CI -0.34 to -0.04, I2=86.2%, P=0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein-creatinine ratio and urinary albumin-creatinine ratio. CONCLUSIONS: These findings suggest that uric acid-lowering treatment may slow CKD progress and reduce protein and albumin excretion. However, larger and properly powered randomized clinical trials with specific CKD populations are needed to confirm these findings.

Polymyxin Acute Kidney Injury: a case of severe tubulopathy.

Polymyxins are antibiotics developed in the 1950s. Polymyxin-induced neurotoxicity has been often described in medical literature. The same cannot be said of nephrotoxicity or tubulopathy in particular. This report describes the case of a patient prescribed polymyxin B to treat a surgical wound infection, which led to significant increases in fractional excretion of calcium, magnesium, and potassium and subsequent persistent decreases in the levels of these ions, with serious consequences for the patient. Severe hypocalcemia, hypomagnesemia, and hypokalemia may occur during treatment with polymyxin. Calcium, magnesium and potassium serum levels must be monitored during treatment to prevent life-threatening conditions.

Hypoparathyroidism and Fahr's syndrome: case series.

Hypoparathyroidism (HP) is a rare metabolic disorder and causes hypocalcemia because parathyroid hormone secretion is inadequate to mobilize calcium from bone and reabsorb calcium from kidney and gut. Anterior neck surgery is the most common cause of acquired HP and autoimmune HP is the next most common form in adults. The duration, severity, and rate of development of hypocalcemia determine the clinical presentation. A variety of organs can be affected by calcification, more frequently kidneys, but also joints, eyes, skin, vasculature, and other organ systems and, although rarely seen, intracerebral calcifications. We report four cases of bilateral basal ganglia calcifications (BGC) also known as Fahr's syndrome related to hypoparathyroidism. Fahr's syndrome is characterized by bilateral symmetrical calcification of areas of the brain that control movements including basal ganglia, thalamus, and others; it is a rare inherited or sporadic neurological disorder with a prevalence of less than 1/1.000.000. Main symptoms related to bilateral BGC include extra-pyramidal and cerebellar disorders, cognitive impairment, epileptic seizures, and psychiatric changes. BGC has been established as a possible outcome of HP. Its prevalence, demonstrated in the HP cohorts, varied significantly from 12 up to 74%. Currently, computed tomography (CT) is the most valuable method for diagnosis. The treatment include symptomatic support and identification of causes, but there is no specific treatment limiting the progression of calcification in the basal ganglia. Especially in HP, an early treatment can prevent calcification and neurophysiological disorders.

A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the Oxidative Stress of Patients with Chronic Kidney Disease.

BACKGROUND: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. OBJECTIVE: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. METHODS: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. RESULTS: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. CONCLUSION: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings. Clinical Trials Registration No.: This study is registered in the Brazilian Record of Clinical Trials (ReBEC), under reference RBR-2bfthr.

Covid-19 (Sars-Cov-2 Infection) Information for Patients with Predialytic Chronic Kidney Disease.

Patients with Chronic Kidney Disease are among those individuals at increased risk for developing more serious forms of Covid-19. This increased risk starts in the pre-dialysis phase of the disease. Providing useful information for these patients, in language that facilitates the understanding of the disease, can help nephrologists and other healthcare professionals to establish a more effective communication with these patients and help minimize contagion and the risks of serious illness in this population.

Recommendations from the Brazilian Society of Nephrology regarding the use of cloth face coverings, by chronic kidney patients in dialysis, during the new coronavirus pandemic (Covid-19).

These recommendations were created after the publication of informative note 3/2020- CGGAP/DESF/SAPS/MS, of April 4, 2020, in which the Brazilian Ministry of Health recommended the use of a cloth mask by the population, in public places. Taking into account the necessary prioritization of the provision of Personal Protective Equipment (PPE) for patients with suspected or confirmed disease, as well as for healthcare professionals, the SBN is favorable concerning the wear of cloth masks by chronic kidney patients in dialysis, in public settings, except in the dialysis setting. The present recommendations have eleven items, related to this rationale, the procedures, indications, contraindications, as well as appropriate fabrics for the mask, and hygiene care to be adopted. These recommendations may change, at any time, in the light of new evidence.

Non-recovery of renal function is a strong independent risk factor associated with mortality in AKI patients.

INTRODUCTION: Acute kidney injury (AKI) is a recurrent complication in the intensive care unit (ICU) and is associated with negative outcomes. OBJECTIVE: To investigate factors associated with mortality in critically ill AKI patients in a South Brazilian ICU. METHODS: The study was observational retrospective involving AKI patients admitted to the ICU between January 2011 and December 2016 of at least 18 years old upon admission and who remained in the ICU at least 48 hours. Comparisons between selected characteristics of survivor and non-survivor groups were done using univariate analysis; multivariate logistic regression was applied to determine factors associated with patient mortality. RESULTS: Of 838 eligible patients, 613 participated in the study. Men represented the majority (61.2%) of the patients, the median age was 53 years, and the global mortality rate was 39.6% (n= 243). Non-recovery of renal function after AKI (OR= 92.7 [38.43 - 223.62]; p <0.001), major surgery-associated AKI diagnosis (OR= 16.22 [3.49 - 75.38]; p <0.001), and the use of vasoactive drugs during the ICU stay (OR = 11.49 [2.46 - 53.70]; p <0.002) were the main factors independently associated with patient mortality. CONCLUSION: The mortality rate observed in this study was similar to that verified in other centers. Non-recovery of renal function was the variable most strongly associated with patient mortality, suggesting that the prevention of factors that aggravate or maintain the AKI episode should be actively identified and mitigated, possibly constituting an important strategy to reduce mortality in AKI patients.

Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients.

INTRODUCTION: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. METHODS: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. RESULTS: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. CONCLUSIONS: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

Good Practice Recommendations from the Brazilian Society of Nephrology to Dialysis Units Concerning the Pandemic of the New Coronavirus (Covid-19).

Dialysis units are environments potentially prone to the spread of Covid-19. Patients cannot suspend treatment, and they often have comorbidities, which assigns them a higher risk and worse prognosis. The Brazilian Society of Nephrology prepared this document of good practices, whose technical recommendations deal with general measures that can be implemented to reduce the risk of transmission and prevent the spread of the disease in the unit.

Renal histological findings in a patient with acute renal injury associated with purpura fulminans: a case report.

INTRODUCTION: Purpura fulminans (PF) is a rapid progressive thrombotic disease in which hemorrhagic infarction of the skin and disseminated intravascular coagulation (DIC) occurs. It can potentially cause acute kidney injury (AKI). However, there is no description in the medical literature of renal histological findings of PF. CASE REPORT: A 20-year-old female patient, previously healthy, was admitted to the emergency department (ED) with odynophagia, fever, generalized myalgia and anuria, which evolved with the appearance of purpuric plaques on the face and limbs. She required dialysis on admission. Laboratorial tests showed anemia, leukocytosis, thrombocytopenia, and elevation of lactic dehydrogenase (LDH). The purpuric lesions became bullous with ruptures and then necrotic and erosive, reaching the dermis, subcutaneous tissue and musculature, until bone exposure. There was no improvement with initial antibiotic therapy aimed at the treatment of meningococcemia. Thrombotic microangiopathy (TMA) and PF were then suspected. The patient remained in daily dialysis, requiring plasmapheresis. After sustained improvement of the thrombocytopenia, she underwent renal biopsy, which was not compatible with TMA, characterizing possible PF. A complete recovery of the renal function was achieved and cutaneous sequels were treated with grafts. CONCLUSION: When thrombotic and hemorrhagic phenomena overlap, obtaining a renal biopsy can be difficult. However, in the presented case, the biopsy allowed the exclusion of AKI caused by TMA, presenting for the first time, histological findings compatible with PF.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation.

INTRODUCTION: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. OBJECTIVES: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. STATISTICAL ANALYSIS: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. RESULTS: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). DISCUSSION: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Is the vitamin D status of patients with COVID-19 associated with reduced mortality? A systematic review and meta-analysis

ABSTRACT To conduct a systematic review and meta-analysis of studies assessing the association between serum vitamin D status and mortality in patients with COVID- 19. We searched PubMed and Embase for studies addressing the association of serum vitamin D levels and COVID-19 mortality published until April 24, 2022. Risk ratios (RRs) and 95% confidence interval (CIs) were pooled using fixed or random effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. The meta-analysis included 21 studies that measured serum vitamin D levels close to the date of admission, of which 2 were case- control and 19 were cohort studies. Vitamin D deficiency was associated with COVID-19 mortality in the overall analysis but not when the analysis was adjusted to vitamin D cutoff levels < 10 or < 12 ng/mL (RR 1.60, 95% CI 0.93-2.27, I2 60.2%). Similarly, analyses including only studies that adjusted measures of effect for confounders showed no association between vitamin D status and death. However, when the analysis included studies without adjustments for confounding factors, the RR was 1.51 (95% CI 1.28-1.74, I2 0.0%), suggesting that confounders may have led to many observational studies incorrectly estimating the association between vitamin D status and mortality in patients with COVID-19. Deficient vitamin D levels were not associated with increased mortality rate in patients with COVID-19 when the analysis included studies with adjustments for confounders. Randomized clinical trials are needed to assess this association.

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials / ¿El tratamiento para reducir el ácido úrico retarda la progresión de la enfermedad renal crónica? Un metaanálisis de ensayos controlados aleatorizados

Introduction: Hyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients. Methods: PubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model. Results: Among 567 studies found, eighteen met the inclusion criteria (n=2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02ml/min/1.73m2 (95%CI 0.41 to 3.63, P=0.014) and −0.19mg/dl (95%CI −0.34 to −0.04, I2=86.2%, P=0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein–creatinine ratio and urinary albumin–creatinine ratio. (AU)

Antecedentes: La hiperuricemia se ha propuesto como un factor independiente en el desarrollo y la progresión de la enfermedad renal crónica (ERC). Sin embargo, el efecto de las terapias para reducir el ácido úrico en el retraso de la progresión de la ERC aún es incierto. Por lo tanto, esta revisión sistémica tiene como objetivo evaluar el efecto de los tratamientos para reducir el ácido úrico sobre los resultados renales en pacientes con ERC antes de la diálisis. Métodos: Se realizaron búsquedas en las bases de datos de PubMed, Cochrane Library y Lilacs hasta el 24 de abril de 2021 en busca de ensayos clínicos aleatorizados de pacientes con ERC en tratamiento para reducir el ácido úrico con inhibidores de la xantina-oxidasa (XO). La diferencia de medias ponderada (DMP) o la diferencia de medias estándar (DME) con el intervalo de confianza (IC) se agruparon mediante un modelo de efectos aleatorizados. Resultados: Entre los 567 estudios encontrados, 18 cumplieron los criterios de inclusión (n=2.463 participantes). En comparación con los pacientes del grupo control, la DMP para la tasa de filtración glomerular (TFG) y los cambios en la creatinina sérica del grupo tratado fueron de 2,02ml/min/1,73m2 (IC del 95%: 0,41 a 3,63, P=0,014) y −0,19mg/dl (IC del 95%: −0,34 a −0,04, I2=86,2%, P=0,011), respectivamente. Los análisis de subgrupos mostraron que la diferencia en el tiempo de seguimiento y el tipo de población con ERC en los estudios puede explicar la controversia sobre el papel de las terapias para reducir el ácido úrico en la progresión de la ERC. El análisis de resultados de TFG y de creatinina por tipos de inhibidores de la XO no mostró diferencias entre el grupo control y el grupo tratado. Las terapias para reducir el ácido úrico se asociaron fuertemente con una disminución del ácido úrico sérico y de la relación proteína-creatinina urinaria y la relación albúmina-creatinina urinaria. (AU)

Polymorphisms in IMPDH2, UGT2B7, and CES2 genes influence the risk of graft rejection in kidney transplant recipients taking mycophenolate mofetil.

The immunosuppressant mycophenolic acid (MPA), derived from the prodrug mycophenolate mofetil (MMF), is a drug used widely by kidney transplant recipients. This drug selectively inhibits inosine monophosphate dehydrogenase that controls the proliferation of lymphocytes, aiding in the prevention of rejection of the transplanted organ. Polymorphisms in key genes involved in MMF metabolism may alter the function of the enzymes encoded by them and contribute to interindividual variability in the response to the drug and its efficacy. The aim of this study was to investigate the association of nine polymorphic variants of eight genes involved in MMF pharmacokinetics, with rejection and adverse effects exhibited by kidney transplant recipients who use this drug. Our sample comprised 145 kidney transplant recipients undergoing post-transplant treatment whose immunosuppressive therapy consisted of MMF and corticosteroid combined or not with a calcineurin inhibitor or mTOR inhibitor. The average age of the patients was 46.9 ±â€¯12.5 years, and they underwent transplantation 7 ±â€¯5.71 years ago. The combination of the T/C and C/C genotypes of the polymorphism rs11706052 (IMPDH2) was associated with a 4.2-fold protection, and the combination of the genotypes A/G and G/G of the polymorphism rs7438135 (UGT2B7) showed a 2.4-fold protection, against rejection. The association of T/C and C/C genotypes in the SNP rs11706052 (IMPDH2) with the occurrence of rejection episodes considering only patients who received immunosuppressive drug MMF associated with cyclosporine or tacrolimus and corticoids, demonstrated association with a protection against rejection 15.6-fold. The T/T genotype of the polymorphism rs2241409 (CES2) was associated with a 7.2-fold increased risk of rejection. Therefore, these polymorphisms that showed a strong association with rejection episodes should be considered in future studies on new prognostic markers for rejection in patients treated with MMF.

Upper gastrointestinal alterations in kidney transplant candidates.

INTRODUCTION: The incidence of gastrointestinal disorders among patients with chronic kidney disease (CKD) is high, despite the lack of a good correlation between endoscopic findings and symptoms. Many services thus perform upper gastrointestinal (UGI) endoscopy on kidney transplant candidates. OBJECTIVES: This study aims to describe the alterations seen on the upper endoscopies of 96 kidney-transplant candidates seen from 2014 to 2015. METHODS: Ninety-six CKD patients underwent upper endoscopic examination as part of the preparation to receive kidney grafts. The data collected from the patients' medical records were charted on Microsoft Office Excel 2016 and presented descriptively. Mean values, medians, interquartile ranges and 95% confidence intervals of the clinic and epidemiological variables were calculated. Possible associations between endoscopic findings and infection by H. pylori were studied. RESULTS: Males accounted for 54.17% of the 96 patients included in the study. Median age and time on dialysis were 50 years and 50 months, respectively. The most frequent upper endoscopy finding was enanthematous pangastritis (57.30%), followed by erosive esophagitis (30.20%). Gastric intestinal metaplasia and peptic ulcer were found in 8.33% and 7.30% of the patients, respectively. H. pylori tests were positive in 49 patients, and H. pylori infection was correlated only with non-erosive esophagitis (P = 0.046). CONCLUSION: Abnormal upper endoscopy findings were detected in all studied patients. This study suggested that upper endoscopy is a valid procedure for kidney transplant candidates. However, prospective studies are needed to shed more light on this matter.