Vitamin D Metabolites Before and After Kidney Transplantation in Patients Who Are Anephric.

RATIONALE & OBJECTIVE: Kidneys are vital for vitamin D metabolism, and disruptions in both production and catabolism occur in chronic kidney disease. Although vitamin D activation occurs in numerous tissues, the kidneys are the most relevant source of circulating active vitamin D. This study investigates extrarenal vitamin D activation and the impact of kidney transplantation on vitamin D metabolism in patients who are anephric. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Adult patients with previous bilateral nephrectomy (anephric) not receiving active vitamin D therapy evaluated at the time of (N=38) and 1 year after (n=25) kidney transplantation. ANALYTICAL APPROACH: Chromatography with tandem mass spectrometry was used to measure vitamin D metabolites. Activity of CYP24A1 [24,25(OH)2D/25(OH)D] and CYP27B1 [1α,25(OH)2D/25(OH)D] is expressed as metabolic ratios. Differences between time points were evaluated by paired t-test or Wilcoxon matched-pairs signed-rank test. RESULTS: At time of transplantation, 1α,25(OH)2D was detectable in all patients (4-36pg/mL). There was a linear relationship between 25(OH)D and 1α,25(OH)2D levels (r=0.58, P<0.001), with 25(OH)D explaining 34% of the variation in 1α,25(OH)2D levels. There were no associations between 1α,25(OH)2D and biointact parathyroid hormone (PTH) or fibroblast growth factor 23 (FGF-23). One year after transplantation, 1α,25(OH)2D levels recovered (+205%), and CYP27B1 activity increased (+352%). Measures of vitamin D catabolism, 24,25(OH)2D and CYP24A1 activity increased 3- to 5-fold. Also, at 12 months after transplantation, 1α,25(OH)2D was positively correlated with PTH (ρ=0.603, P=0.04) but not with levels of 25(OH)D or FGF-23. LIMITATIONS: Retrospective, observational study design with a small cohort size. CONCLUSIONS: Low-normal levels of 1α,25(OH)2D was demonstrated in anephric patients, indicating production outside the kidneys. This extrarenal CYP27B1 activity may be more substrate driven than hormonally regulated. Kidney transplantation seems to restore kidney CYP27B1 and CYP24A1 activity, as evaluated by vitamin D metabolic ratios, resulting in both increased vitamin D production and catabolism. These findings may have implications for vitamin D supplementation strategies in the setting of kidney failure and transplantation. PLAIN-LANGUAGE SUMMARY: Vitamin D activation occurs in multiple tissues, but the kidneys are considered the only relevant source of circulating levels. This study investigates vitamin D activation outside the kidneys by measuring vitamin D metabolites in 38 patients without kidneys. Active vitamin D was detectable in all patients, indicating production outside of the kidneys. There was a strong relationship between active and precursor vitamin D levels, but no association with mineral metabolism hormones, indicating that vitamin D production was more substrate dependent than hormonally regulated. One year after kidney transplantation, active vitamin D levels increased 2-fold and breakdown products increased 3-fold, indicating that production and degradation of the hormone recovers after kidney transplantation. These findings are relevant for future research into vitamin D supplementation in kidney failure.

Left atrial appendage occlusion in patients suffering from advanced chronic kidney disease (stage 4 and 5). Long-term follow-up.

INTRODUCTION AND OBJECTIVES: Advanced chronic kidney disease (A-CKD) combined with atrial fibrillation increases the risk of both thrombogenic and bleeding events. Left atrial appendage occlusion (LAAO) may be an alternative to oral anticoagulation to prevent thromboembolic events. We aimed to evaluate the outcomes of LAAO in patients with A-CKD. METHODS: Comparison at long-term follow-up of patients diagnosed with and without A-CKD (eGFR<30 mL/min/1.73 m2 ) who underwent LAAO between 2009 and May 2022. RESULTS: Five hundred seventy-three patients were included. Eighty-one (14%) were diagnosed with A-CKD. There were no differences in sex, age, and cardiovascular risk factors, except for diabetes which was more frequent in patients with A-CKD. The control group had higher rates of stroke, both ischemic and hemorrhagic. There were no differences in the CHA2 DS2 -VASc score, although A-CKD patients had a higher bleeding risk according to the HASBLED scale. Global procedural success was 99.1%. At follow-up, there were no differences in stroke rate: at 1-year (HR: 1.22, IC-95%: 0.14-10.42, p = 0.861); at 5-years (HR: 0.60, IC-95%: 0.08-4.58, p = 0.594). Although bleeding events were higher in the A-CKD group, no differences were found in major bleeding (defined BARC ≥ 3) at 1-year (HR: 1.34, IC-95%: 0.63-2.88, p = 0.464) or at 5-years follow-up (HR: 1.30, IC-95%: 0.69-2.48, p = 0.434). Mortality rate at 5 years was higher in the A-CKD patients (HR: 1.84, IC-95%: 1.18-2.87, p = 0.012). CONCLUSIONS: LAAO is an effective and safe treatment in A-CKD patients to prevent ischemic events and bleeding. This strategy could be an alternative to oral anticoagulation in this high-risk group of patients.

Clinical implications of primary "occult" vesicoureteral reflux in male children.

OBJECTIVES: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR. MATERIALS AND METHODS: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria. RESULTS: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI. CONCLUSION: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR. CLINICAL RELEVANCE STATEMENT: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention.

Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trøndelag Health Study in Norway.

PURPOSE: Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. METHODS: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. RESULTS: Participants with eGFR < 30 ml/min/1.732 had HR 3.35 for BSI (95% confidence intervals (CI) 2.12-5.3) and HR 2.94 for sepsis (95% CI 1.82-4.8) compared to normal eGFR (≥ 90 ml/min/1.732). HRs of death from BSI and sepsis were 4.2 (95% CI 1.71-10.4) and 4.1 (95% CI 1.88-8.9), respectively. Participants with severely increased albuminuria (ACR > 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30-5.6) and 3.14 for sepsis (95% CI 1.94-5.1) compared to normal albumin excretion (ACR < 3 mg/mmol). HRs of death were 2.67 (95% CI 0.82-8.7) and 2.16 (95% CI 0.78-6.0), respectively. CONCLUSION: In this large population-based cohort study, CKD was clearly associated with an increased risk of BSI and sepsis and related death.

Primary sclerosing cholangitis causally affects kidney function decline: A Mendelian randomization study.

BACKGROUND AND AIM: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long-term detrimental effects on kidney function. METHODS: Two-sample summary-level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC-specific multi-trait analyzed genome-wide association study (GWAS) of European ancestry. Summary-level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random-effects inverse-variance weighted (MR-IVW), and a series of pleiotropy-robust analyses were performed to investigate the causal effects and ascertain their robustness. RESULTS: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log-transformed eGFR (MR-IVW; beta = -0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR-IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR-IVW; odds ratio = 1.07; 95% confidence interval = 1.06-1.08; P < 0.001). The main findings were supported by pleiotropy-robust analysis, including MR-Egger with bootstrapped error and weighted median. CONCLUSIONS: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.

BACKGROUND: In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). METHODS: This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. RESULTS: The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. CONCLUSIONS: In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.

Case report of a child with nephronophthisis from South Africa.

BACKGROUND: Nephronophthisis (NPHP) is an autosomal recessive disorder with a subset of patients presenting with extrarenal manifestations such as retinal degeneration, cerebella ataxia, liver fibrosis, skeletal abnormalities, cardiac malformations, and lung bronchiectasis. However, the involvement of other organ systems has also been documented. Extrarenal manifestations occur in approximately 10-20% of patients. In developed countries, it has been reported as one of the most common causes of monogenic chronic kidney failure (CKF) during the first three decades of life, with more than 25 genes associated with this condition. The current treatment options for managing NPHP include supportive care, management of complications, and kidney replacement therapy when necessary. The index patient is a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain. Her elder sister, TN, who was 17 years old, was diagnosed with CKF and noted to have persistently elevated liver enzymes (gamma-glutamyl transferase, alanine, and aspartate transaminases). Following genetic testing, her elder sister was shown to have Nephronophthisis Type 3, and a liver biopsy showed early fibrotic changes. Subsequent genetic testing confirmed the index patient as having NPHP Type 3. A kidney biopsy showed focal sclerosed glomeruli with patchy areas of tubular atrophy and related tubulointerstitial changes in keeping with NPHP. We present the first confirmatory case of NPHP from South Africa based on histopathology and genetic testing in a 10-year-old Caucasian female who presented with recurrent attacks of abdominal pain, whose elder sister also presented with CKF and early liver fibrosis, confirmed on biopsy and genetic testing. CONCLUSION: In low-middle-income countries, genetic testing should be undertaken whenever possible to confirm the diagnosis of NPHP, especially in those with a suggestive biopsy or if there is CKF of unknown aetiology with or without extra-renal manifestations.

Effectiveness of educational interventions for nurses caring for patients with chronic kidney disease in improving nurse outcomes: A systematic review.

AIM: The aim of the study was to evaluate the effectiveness of educational interventions for nurses caring for patients with chronic kidney disease in improving knowledge, nurse-patient interaction, performance, skills competence and clinical decision-making. DESIGN: Systematic review. METHODS: Search of literature for randomised controlled trials, quasi-experimental studies and pre-experimental studies on chronic kidney disease-related educational interventions for nurses was conducted across 10 databases. Two reviewers independently screened articles, appraised studies and extracted data. DATA SOURCES: PubMed, Cochrane, Embase, CINAHL Complete, ERIC, Social Science Database, ASSIA, Scopus, Web of Science and ProQuest Thesis and Dissertations Global databases were searched from date of inception to 21 December 2022. RESULTS: Three randomised controlled trials and eight pre-experimental studies were included in this review. Synthesis without meta-analysis was conducted due to high heterogeneity among studies. Interventions with teaching sessions, learning activities, self-study modules, discussion and a web-based training system were effective in improving nurses' knowledge, nurse-patient interaction, performance, skills competence and clinical decision-making. Patients experienced an improvement in nurse-patient interaction and no significant decrease in overall quality of life. CONCLUSION: This review has shown the effectiveness of educational interventions for nurses caring for people with chronic kidney disease in improving outcomes for both nurses and patients, with sustained improvements up to a period of 1 year. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Study findings can guide the scope of future training for nurses caring for patients with chronic kidney disease. IMPACT: Nurses often lack in-service training on how to improve care for patients with chronic kidney disease. This study found that training nurses on how to care for such patients can improve outcomes for nurses, which can translate to higher quality of patient care. REPORTING METHOD: This paper adhered to the synthesis without meta-analysis (SWiM) reporting guideline.

Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6.

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.

Quality of life of patients after kidney transplant: ADHERE Brazil multicenter cross-sectional study.

BACKGROUND: Quality of life (QoL) is a measure to evaluate kidney transplant (KT) results. AIM: To describe the QoL profile in a larger sample of Brazilian patients who underwent KT according to age, sex, and access to KT. METHODS: We conducted a secondary data analysis of the ADHERE BRAZIL multicenter cross-sectional study including 1105 patients from 20 centers, considering KT access region and transplant activity. QoL was assessed by the WHOQOL-BREF. Data was compared using Generalized Estimating Equations. RESULTS: Overall, 58.5 % of the patients were men, mean age of 47.6 ± 12.6 years. The general QoL score was 81 ± 15.1, 58.6 ± 11.6 for physical, 65.5 ± 11.4 for psychological, 68.3 ± 17.1 for social relationships, and 64.2 ± 13.3 for environmental domain. Higher QoL scores were observed in men compared to women in three WHOQOL-BREF domains: psychological (OR:2.62; CI, 1.29 ̶ 3.95, p < 0.0001), social relationships (OR:3.21; CI, 1.2 ̶ 5.23, p = 0.002) and environmental (OR:3.79; CI:2.23 ̶ 5.35, p < 0.0001). Younger patients (18-44 years) had higher scores in the psychological (OR:-2.69; CI, -4.13 ̶ -1.25; p < 0.001; OR:-3.52; CI, -5.39 ̶ -1.66; p < 0.001) and social (OR:-3.46; CI, -5.64 ̶ -1.27; p = 0.002; OR:-7.17; CI, -10 ̶ -4.35; p < 0.0001) domains than older ones (45-59 and > 60 years, respectively). Patients from higher KT access region had higher scores in environmental domain (OR:3.53; CI, 0.28 ̶ 6.78; p = 0.033). CONCLUSIONS: Featuring the results of KT under patient view, the physical and social relationships domains were the most and least affected, respectively. Lower QoL subgroups (females and age > 45 years) should be targeted in future multi-professional interventions.

A Chinese Multi-Specialty Delphi Consensus to Optimize RAASi Usage and Hyperkalaemia Management in Patients with Chronic Kidney Disease and Heart Failure.

Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia (HK), there is therefore a need to establish a multi-specialty approach to optimal renin-angiotension-aldosterone system inhibitors (RAASi) usage and HK management in patients with chronic kidney disease (CKD) & heart failure (HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF. Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique. The group then created a list of 41 statements for a consensus questionnaire, which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China. Consensus was assessed using a modified Delphi technique, with agreement defined as "strong" (≥75% and <90%) and "very strong" (≥90%). The steering group, data collection, and analysis were aided by an independent facilitator. Results A total of 150 responses from 21 provinces across China were recruited in the survey. Respondents were comprised of an even split (n=75, 50%) between cardiologists and nephrologists. All 41 statements achieved the 75% consensus agreement threshold, of which 27 statements attained very strong consensus (≥90% agreement) and 14 attained strong consensus (agreement between 75% and 90%). Conclusion Based on the agreement levels from respondents, the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.

Safety of Immune Checkpoint Inhibitors in Patients With Advanced Chronic Kidney Disease: A Retrospective Cohort Study.

BACKGROUND: Clinical trials of immune checkpoint inhibitors (ICIs) often do not include patients with advanced chronic kidney disease (CKD). We aimed to determine the safety of ICIs in patients with cancer and advanced CKD (stages 4-5 CKD, estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2). PATIENTS AND METHODS: Patients with advanced CKD from the Mass General Brigham network who received ICIs (n = 91) were compared against those receiving nephrotoxic (n = 113) and non-nephrotoxic (n = 130) antineoplastic therapies, respectively. Rates of new-onset kidney failure (end-stage kidney disease or sustained eGFR ≤10 mL/minute/1.73 m2) and AKI were compared. Among ICI-treated patients, we modeled Fine-Gray subdistribution hazards to compare immune-related adverse event (irAE) risk and used Kaplan-Meier analysis to compare overall survival in patients with advanced CKD to those with eGFR ≥30 mL/minute/1.73 m2. RESULTS: Rates of new-onset kidney failure were similar at 1 year following initiation of ICIs (10.0%), nephrotoxic (6.2%), and non-nephrotoxic antineoplastic therapies (9.3%) (P = .28). AKI rates were also similar: 17.5%, 17.6%, and 20% of patients in each cohort, respectively (P = .87). Advanced CKD did not increase the risk of developing irAEs (adjusted hazard ratio [HR] 1.28, 95% CI, 0.91-1.81). However, patients with advanced CKD who received ICIs had a decreased overall survival compared with patients with eGFR ≥30 mL/minute/1.73 m2 (HR 1.30 for death, 95% CI, 1.02-1.66, P = .03). CONCLUSION: ICIs are not associated with increased risk of AKI or new-onset kidney failure compared with other antineoplastic therapies in patients with advanced CKD. Advanced CKD did not increase the risk of extra-renal irAEs, although these patients suffered from lower overall survival.

Texture analysis of native T1 images as a novel method for non-invasive assessment of heart failure with preserved ejection fraction in end-stage renal disease patients.

OBJECTIVES: To explore the diagnostic potential of texture analysis applied to native T1 maps obtained from cardiac magnetic resonance (CMR) images for the assessment of heart failure with preserved ejection fraction (HFpEF) among patients with end-stage renal disease (ESRD). METHODS: This study, conducted from June 2018 to November 2020, included 119 patients (35 on hemodialysis, 55 on peritoneal dialysis, and 29 with kidney transplants) in Renji Hospital. Native T1 maps were assessed with texture analysis, using a freely available software package, in participants who underwent cardiac MRI at 3.0 T. Four texture features, selected by dimension reduction specific to the diagnosis of HFpEF, were analyzed. Multivariate logistic regression was performed to examine the independent association between the selected features and HFpEF in ESRD patients. RESULTS: Seventy-six of 119 patients were diagnosed with HFpEF. Demographic, laboratory, cardiac MRI, and echocardiogram characteristics were compared between HFpEF and non-HFpEF groups. The four texture features that were analyzed showed statistically significant differences between groups. In multivariate analysis, age, left atrial volume index (LAVI), and sum average 4 (SA4) turned out to be independent predictors for HFpEF in ESRD patients. Combining the texture feature, SA4, with typical predictive factors resulted in higher C-index (0.923 vs. 0.898, p = 0.045) and a sensitivity and specificity of 79.2% and 95.2%, respectively. CONCLUSIONS: Texture analysis of T1 maps adds diagnostic value to typical clinical parameters for the assessment of heart failure with preserved ejection fraction in patients with end-stage renal disease. KEY POINTS: • Non-invasive assessment of HFpEF can help predict prognosis in ESRD patients and help them take timely preventative measures. • Texture analysis of native T1 maps adds diagnostic value to the typical clinical parameters for the assessment of HFpEF in patients with ESRD.

Echocardiogram screening in pediatric dialysis and transplantation.

Transthoracic echocardiography is commonly used to identify structural and functional cardiac abnormalities that can be prevalent in childhood chronic kidney failure (KF). Left ventricular mass (LVM) increase is most frequently reported and may persist post-kidney transplant especially with hypertension and obesity. While systolic dysfunction is infrequently seen in childhood chronic KF, systolic strain identified by speckle tracking echocardiography has been frequently identified in dialysis and it can also persist post-transplant. Echocardiogram association with long-term outcomes has not been studied in childhood KF but there are many adult studies demonstrating associations between increased LVM, systolic dysfunction, strain, diastolic dysfunction, and cardiovascular events and mortality. There has been limited study of interventions to improve echocardiogram status. In childhood, improved blood pressure has been associated with better LVM, and conversion from hemodialysis to hemodiafiltration has been associated with better diastolic and systolic function. Whether long-term cardiac outcomes are also improved with these interventions is unclear. Echocardiography is a well-established technique, and regular use in childhood chronic KF seems justified. A case can be made to extend screening to include speckle tracking echocardiography and intradialytic studies in high-risk populations. Further longitudinal studies including these newer echocardiogram modalities, interventions, and long-term outcomes would help clarify recommendations for optimal use as a screening tool.

Short-term safety and efficacy of escalating doses of atorvastatin for dyslipidemia in children with predialysis chronic kidney disease stage 2-5.

BACKGROUND: Dyslipidemia is a potentially modifiable risk factor in patients with chronic kidney disease (CKD). Information on the safety and efficacy of statins in pediatric CKD is limited. METHODS: Patients with CKD stage 2-5 and aged 5-18 years with low-density lipoprotein cholesterol (LDL-C) > 130 mg/dL and/or non-high-density lipoprotein cholesterol (non-HDL-C) > 145 mg/dL were enrolled from September 2019 to February 2021. All patients were administered atorvastatin 10 mg/day, which was escalated to 20 mg/day if LDL-C remained > 100 mg/dL and/or non-HDL-C > 120 mg/dL at 12 weeks. Proportion of patients achieving target lipid levels (LDL-C ≤ 100 mg/dL and non-HDL-C ≤ 120 mg/dL) and adverse events were assessed at 24 weeks. RESULTS: Of 31 patients enrolled, target lipid levels were achieved in 45.2% (95% CI 27.8-63.7%) at 24 weeks; 22 patients required dose escalation to 20 mg at 12 weeks. There was no difference in median lipid level reduction with 10 (n = 9) versus 20 mg/day (n = 22, P = 0.3). Higher baseline LDL-C (OR 1.06, 95% CI 1.00-1.11) and older age (OR 36.5, 95% CI 2.57-519.14) were independent predictors of failure to achieve target lipid levels with 10 mg/day atorvastatin. None had persistent rise in AST/ALT > 3 times upper normal limit (UNL) or CPK > 10 times UNL. No differences were noted in adverse events due to atorvastatin 10 or 20 mg/day. CONCLUSION: Atorvastatin (10-20 mg/day) administered for 24 weeks was safe and effectively reduced LDL-C and non-HDL-C in children with CKD stages 2-5. Patients with higher baseline LDL-C required higher doses to achieve the target. A higher resolution version of the Graphical abstract is available as Supplementary information.

The real world experience of pediatric primary hyperoxaluria patients in the PEDSnet clinical research network.

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

Association between chronic kidney disease and periodontitis. A systematic review and metanalysis.

OBJECTIVES: Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages. MATERIALS AND METHODS: MEDLINE, Cochrane Central Register of Trials and EMBASE, up to April 4, 2021 were searched. RCTs, prospective and retrospective cohort studies, case-control studies and cross-sectional studies were considered. JBI's Critical Appraisal Tool for risk of bias assessment was used. The risk of PD was calculated using the Mantel-Haenszel odds ratios (MH-OR); weighted mean difference for clinical attachment level (CAL) and periodontal probing depth (PPD) were also evaluated. RESULTS: Out of 1949 titles screened, 142 full texts were evaluated and 17 studies were included. CKD was associated to higher risk of PD (MH-OR = 2.36, [95% C.I. 1.25, 4.44]; p = 0.008), higher mean CAL (WMD = 0.41 mm [95% C.I. 0.22, 0.60]; p < 0.0001) and mean PPD (WMD = 0.25 mm [95% C.I. 0.03, 0.47]; p = 0.02) compared to healthy individuals. Severe CKD (stages 4-5 vs 2-3) resulted at higher risk of PD (MH-OR = 2.21, [95% C.I. 1.07, 4.54]; p = 0.03). Heterogeneity and risk of bias were high. CONCLUSIONS: An association between PD and CKD was found. It could be appropriate to consider PD a frequent CKD comorbidity.

Autosomal dominant polycystic kidney disease in Colombia.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) that requires dialysis. Knowing geographical clusters can be critical for early diagnosis, progression control, and genetic counseling. The objective was to establish the prevalence, geographic location, and ethnic groups of patients with ADPKD who underwent dialysis or kidney transplant in Colombia between 2015 and 2019. METHODS: We did a cross-sectional study with data from the National Registry of Chronic Kidney Disease (NRCKD) managed by the High-Cost Diseases Fund (Cuenta de Alto Costo [CAC] in Spanish) between July 1, 2015, and June 30, 2019. We included Colombian population with CKD with or without renal replacement therapy (RRT) due to ADPKD. Crude and adjusted prevalence rates were estimated by state and city. RESULTS: 3,339 patients with ADPKD were included, period prevalence was 9.81 per 100,000 population; there were 4.35 cases of RRT per 100,000 population, mean age of 52.58 years (± 13.21), and 52.78% women. Seventy-six patients were Afro-Colombians, six were indigenous, and one Roma people. A total of 46.07% began scheduled dialysis. The highest adjusted prevalence rate was in Valle del Cauca (6.55 cases per 100,000 population), followed by Risaralda, and La Guajira. Regarding cities, Cali had the highest prevalence rate (9.38 cases per 100,000 population), followed by Pasto, Medellin, and Bucaramanga. CONCLUSIONS: ADPKD prevalence is lower compared to Europe and US; some states with higher prevalence could be objective to genetic prevalence study.

Prevalence and risk factors of Strongyloides stercoralis in haemodialysis in Cochabamba, Bolivia: a cross-sectional study.

BACKGROUND: Strongyloidiasis is an infectious disease that can be fatal in immunocompromised patients. Patients with end-stage renal failure who are on dialysis have a considerably weakened immune system, and organ transplantation is a major risk factor for severe strongyloidiasis. Knowledge of the local epidemiology in tropical and subtropical areas is an essential prerequisite for designing an appropriate strategy to prevent this potentially lethal complication. In this study, we aimed to estimate the prevalence and associated risk factors of S. stercoralis infection in patients on dialysis in Cochabamba, Bolivia. METHODS: A cross-sectional study was carried out among patients undergoing haemodialysis in Cochabamba (elevation 2,500 m, temperate climate), collecting information on socio-demographic, lifestyle, and clinical variables, and using one coproparasitological technique (the modified Baermann technique) and one serological (ELISA) test for S.stercoralis diagnosis. RESULTS: In total, 149 patients participated in the study (mean age = 51.4 years, 48.3% male). End-stage renal disease was predominantly (59%) of hypertensive and/or diabetic origin. The positive serological prevalence was 18.8% (95% CI: 13.3%-25.9%). Based on the sensitivity and specificity of the ELISA test, the estimate of the actual prevalence was 15.1% (95% CI: 9.4%-20.7%). Stool samples of 105 patients (70.5%) showed a coproparasitological prevalence of 1.9% (95% CI: 0.52%-6.68%). No potential risk factors were significantly associated with S. stercoralis infection. CONCLUSIONS: We found a high seroprevalence of S. stercoralis in Bolivian patients undergoing haemodialysis in Cochabamba. We recommend presumptive antiparasitic treatment at regular intervals to avoid the potentially fatal complications of severe strongyloidiasis.