An unusual case of adult-onset still's disease complicated with anti-complement factor H antibodies associated atypical haemolytic uraemic syndrome.

BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing. CASE PRESENTATION: A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml). CONCLUSION: Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.

Frailty in patients on dialysis.

Frailty is a condition that is frequently observed among patients undergoing dialysis. Frailty is characterized by a decline in both physiological state and cognitive state, leading to a combination of symptoms, such as weight loss, exhaustion, low physical activity level, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but also are at higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, frailty has no cure. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and chronic kidney disease-related complications, reducing polypharmacy by deprescription, personalizing dialysis prescription, and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.

Environmental pollution to kidney disease: an updated review of current knowledge and future directions.

Environmental pollution significantly impacts global disease burden. However, the contribution of environmental pollution to kidney disease is often overlooked in nephrology. This review examines the growing body of research demonstrating the significant impacts of environmental pollutants, with a focus on air pollution as a primary factor, and acknowledges the roles of other pollutants, such as heavy metals, in the development and progression of kidney diseases. Short-term exposure to air pollution is linked with an increased risk of kidney disease-related events, including hospital admissions, and death, predominantly occurring in vulnerable populations. In contrast, long-term exposure, even at low to moderate levels, may lead to progressive pathophysiological changes, such as chronic systemic inflammation and oxidative stress, that contribute to the development of kidney disease. Additionally, air pollution may exacerbate traditional kidney disease risk factors such as hypertension and diabetes, thereby accelerating disease progression. The review also explores how climate change may interact with various pollutants, including air pollution, influencing kidney disease indirectly. The examined evidence underscores the urgent need for an interdisciplinary approach to research further into environmental kidney disease. Environmental health policies could play a crucial role in prevention, intervention, and the improvement of kidney health worldwide.

Staphylococcus lugdunensis Peritoneal Dialysis-Related Peritonitis: A Matched Comparative Analysis.

Rationale & Objective: Staphylococcus lugdunensis (S lugdunensis) is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus (S aureus). No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared with those with S aureus peritonitis. We aim to evaluate the clinical course of peritonitis as caused by these organisms. Study Design: A retrospective matched comparative analysis involving a single tertiary center from July 2000 to July 2020. Setting & Participants: Forty-eight episodes of S aureus peritonitis were matched to 19 cases of S lugdunensis peritonitis. Analytical Approach: The cases were individually matched for year of peritonitis, sex, age (±10 years), and Charlson Comorbidity Index (±3). A comparative analysis was performed between the 2 organisms. The outcome includes responses at day 5 of peritonitis and the rate of complete response. Results: There is a higher predilection of diabetes in those with S aureus peritonitis than in those with S lugdunensis (64.6% vs 31.6%; P = 0.03). Patients with S aureus peritonitis also have a much higher total cell count at presentation (4,463.9 ± 5,479.5 vs 1,807.9 ± 3,322.7; P = 0.05); a higher prevalence of poor response at day 5 (50.0% vs 15.8%; P = 0.03); a lower rate of complete response (64.6% vs 94.7%; P = 0.01) and are more prone to relapse with the same organism (29.2% vs 0%, respectively; P = 0.01) as compared to those with S lugdunensis. Limitations: The result of this small retrospective study involving a single center may not be generalizable to other centers. There is also no data for comparative analysis on other coagulase-negative staphylococci such as Staphylococcus epidermidis, which belongs to the same family as S lugdunensis. Conclusions: Although S aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. This largest case series of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis peritonitis.

Staphylococcus lugdunensis is a coagulase-negative staphylococcus species that has been increasingly recognized to cause serious infections with virulence resembling Staphylococcus aureus. No studies have evaluated the characteristics and outcomes of patients with S lugdunensis peritoneal dialysis-related peritonitis compared those with S aureus peritonitis. This largest retrospective matched comparative analysis of S lugdunensis peritonitis enabled better characterization of clinical features and outcomes of patients with S lugdunensis. Our result suggested that although S. aureus peritonitis is more virulent with significant morbidity, S lugdunensis can cause similarly serious peritonitis. Regardless, S lugdunensis remains susceptible to most antibiotics and penicillin group, penicillin G in particular, can be considered as the first line antibiotic.

Gut permeability, circulating bacterial fragments and measures of congestion in peritoneal dialysis.

Background: Limited data exist on the association between gut permeability, circulating bacterial fragment and volume overload in peritoneal dialysis (PD) patients. We measured circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels, and evaluate their association with the clinical outcomes in PD patients. Methods: This was a single-center prospective study on 108 consecutive incident PD patients. Plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technique and patient survival, secondary outcomes were hospitalization data. Results: There was no significant correlation between plasma endotoxin and bacterial DNA, and serum NT-proBNP, calprotectin and zonulin levels. The Homeostatic Model Assessment for Insulin Resistance (HOMA)-2ß index, which represents insulin resistance, positively correlated with plasma bacterial DNA (r = 0.421, P < .001) and calprotectin levels (r = 0.362, P = .003), while serum NT-proBNP level correlated with the severity of volume overload and residual renal function. Serum NT-proBNP level was associated with technique survival even after adjusting for confounding factors [adjusted hazard ratio (aHR) 1.030, 95% confidence interval 1.009-1.051]. NT-proBNP level was also associated with patient survival by univariate analysis, but the association became insignificant after adjusting for confounding factors (aHR 1.010, P = .073). Similarly, NT-proBNP correlated with the number of hospitalizations and duration of hospitalization by univariate analysis, but the association became insignificant after adjusting for confounding factors. Conclusion: There was no correlation between markers of gut permeability, circulating bacterial fragments and measures of congestion in PD patients. Bacterial fragments levels and gut permeability are both associated with insulin resistance. Serum NT-proBNP level is associated with the severity of volume overload and technique survival. Further studies are required to delineate the mechanism of high circulating bacterial fragment levels in PD patients.

Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

Urinary podocyte markers in diabetic kidney disease.

Podocytes are involved in maintaining kidney function and are a major focus of research on diabetic kidney disease (DKD). Urinary biomarkers derived from podocyte fragments and molecules have been proposed for the diagnosis and monitoring of DKD. Various methods have been used to detect intact podocytes and podocyte-derived microvesicles in urine, including centrifugation, visualization, and molecular quantification. Quantification of podocyte-specific protein targets and messenger RNA levels can be performed by Western blotting or enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. At present, many of these techniques are expensive and labor-intensive, all limiting their widespread use in routine clinical tests. While the potential of urinary podocyte markers for monitoring and risk stratification of DKD has been explored, systematic studies and external validation are lacking in the current literature. Standardization and automation of laboratory methods should be a priority for future research, and the added value of these methods to routine clinical tests should be defined.

Urinary podocyte stress marker as a prognostic indicator for diabetic kidney disease.

BACKGROUND: Diabetic kidney diseases (DKD) is a the most common cause of end-stage kidney disease (ESKD) around the world. Previous studies suggest that urinary podocyte stress biomarker, e.g. podocin:nephrin mRNA ratio, is a surrogate marker of podocyte injury in non-diabetic kidney diseases. METHOD: We studied 118 patients with biopsy-proved DKD and 13 non-diabetic controls. Their urinary mRNA levels of nephrin, podocin, and aquaporin-2 (AQP2) were quantified. Renal events, defined as death, dialysis, or 40% reduction in glomerular filtration rate, were determined at 12 months. RESULTS: Urinary podocin:nephrin mRNA ratio of DKD was significantly higher than the control group (p = 0.0019), while urinary nephrin:AQP2 or podocin:AQP2 ratios were not different between groups. In DKD, urinary podocin:nephrin mRNA ratio correlated with the severity of tubulointerstitial fibrosis (r = 0.254, p = 0.006). and was associated with the renal event-free survival in 12 months (unadjusted hazard ratio [HR], 1.523; 95% confidence interval [CI] 1.157-2.006; p = 0.003). After adjusting for clinical and pathological factors, urinary podocin:nephrin mRNA ratio have a trend to predict renal event-free survival (adjusted HR, 1.327; 95%CI 0.980-1.797; p = 0.067), but the result did not reach statistical significance. CONCLUSION: Urinary podocin:nephrin mRNA ratio has a marginal prognostic value in biopsy-proven DKD. Further validation is required for DKD patients without kidney biopsy.

Impact of Body Composition and Anemia on Accuracy of a Real-Time Continuous Glucose Monitor in Diabetes Patients on Continuous Ambulatory Peritoneal Dialysis.

Continuous glucose monitoring (CGM) is proposed as an alternative for glycemic assessment in peritoneal dialysis, but volume overload and anemia may affect sensor accuracy. This is an exploratory analysis of a study of Guardian Connect™ with Guardian Sensor™ 3 in 30 participants with diabetes on continuous ambulatory peritoneal dialysis (CAPD) (age [mean ± standard deviation] 64.7 ± 5.6 years, 23 men, body mass index [BMI] 25.4 ± 3.9 kg/m2, blood hemoglobin [Hb] 10.7 ± 1.3 g/dL). The mean absolute relative difference (MARD) was calculated between paired sensor and YSI 2300 STAT venous glucose readings (n = 941) during an 8-h in-clinic session with glucose challenge. Body composition was evaluated using bioimpedance. The overall MARD was 10.4% (95% confidence interval 9.6-11.7). There were no correlations between BMI, extracellular water, relative hydration index, and lean or fat mass with MARD. No correlations were observed between MARD and Hb (r = 0.016, P > 0.05). In summary, this real-time CGM demonstrated good accuracy in CAPD with minimal influence from body composition and anemia.

Dietary Micronutrient Intake and Its Relationship with the Malnutrition-Inflammation-Frailty Complex in Patients Undergoing Peritoneal Dialysis.

BACKGROUND: The relationship between dietary patterns and the malnutrition-inflammation-frailty complex in patients undergoing peritoneal dialysis (PD) is currently unknown. Our objective was to measure dietary nutrient intake and evaluate its association with malnutrition, inflammation, and frailty. METHODS: We prospectively recruited adult PD patients. We assessed their dietary nutrient intake using a food frequency questionnaire. Frailty, malnutrition, and inflammation were evaluated by validated Frailty Score (FQ), Subjective Global Assessment (SGA), and Malnutrition-Inflammation Score (MIS). RESULTS: A total of 209 patients were recruited for the study. Among them, 89 patients (42.6%) had an insufficient protein intake, and 104 patients (49.8%) had an insufficient energy intake. Additionally, 127 subjects were identified as frail, characterized by being older (61.9 ± 9.5 vs. 55.6 ± 12.8, p < 0.001), malnourished (SGA: 21.0 ± 2.7 vs. 22.7 ± 3.1, p < 0.001), and having a high inflammation burden (MIS: 10.55 ± 3.72 vs. 7.18 ± 3.61, p < 0.001). There was a significant correlation between dietary zinc intake and body mass index (r = 0.31, p < 0.001), SGA (r = 0.22, p = 0.01), and MIS (r = -0.22, p = 0.01). In the multivariate model, a higher dietary zinc intake predicted a higher SGA (beta 0.03, p = 0.003) and lower FQ (beta -0.38, p < 0.001) and MIS (beta -0.14, p < 0.001), indicating a better nutrition, less frail and inflamed state. A higher dietary zinc intake was also associated with a lower odds of being frail (adjusted odds ratio 0.96, p = 0.009). CONCLUSION: Dietary inadequacy and micronutrient deficiency are common among the PD population. Dietary zinc intake is independently associated with an improved nutrition, physical condition, and reduced inflammatory state.

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy.

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (-1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted.

A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis.

Nanomedicines for treating chronic kidney disease (CKD) are on the horizon, yet their delivery to renal tubules where tubulointerstitial fibrosis occurs remains inefficient. We report a folic acid-conjugated gold nanoparticle that can transport into renal tubules and treat tubulointerstitial fibrosis in mice with unilateral ureteral obstruction. The 3-nm gold core allows for the dissection of bio-nano interactions in the fibrotic kidney, ensures the overall nanoparticle (~7 nm) to be small enough for glomerular filtration, and naturally inhibits the p38α mitogen-activated protein kinase in the absence of chemical or biological drugs. The folic acids support binding to selected tubule cells with overexpression of folate receptors and promote retention in the fibrotic kidney. Upon intravenous injection, this nanoparticle can selectively accumulate in the fibrotic kidney over the nonfibrotic contralateral kidney at ~3.6% of the injected dose. Delivery to the fibrotic kidney depends on nanoparticle size and disease stage. Notably, a single injection of this self-therapeutic nanoparticle reduces tissue degeneration, inhibits genes related to the extracellular matrix, and treats fibrosis more effectively than standard Captopril therapy. Our data underscore the importance of constructing CKD nanomedicines based on renal pathophysiology.

Role of inflammatory burden and treatment on joint space width in psoriatic arthritis-a high-resolution peripheral quantitative computed tomography study.

BACKGROUND: To investigate the relationship between disease-related parameters and joint space width (JSW) on high-resolution peripheral quantitative computed tomography (HR-pQCT) in psoriatic arthritis (PsA) patients. METHODS: PsA patients who underwent HR-pQCT examination of the second to fourth metacarpophalangeal joint (MCPJ 2-4) were recruited in this cross-sectional study. The joint space metrics included joint space volume (JSV), mean, minimum, and maximum JSW, JSW asymmetry, and distribution. Correlation analysis and multivariable linear regression models were used to determine the association between disease-related variables and JSW. RESULTS: Sixty-seven patients [37 (55.2%) males; median (IQR) age: 57.0 (53.0, 63.0); median disease duration: 21 (16, 28) years] were included in this analysis. Multivariable linear regression analysis demonstrated that males had larger JSV (MCPJ 2-4), mean (MCPJ 4), and maximum JSW (MCPJ 3). Longer disease duration (MCPJ 2-3) and higher ESR values (MCPJ 3) were negatively associated with mean and maximum JSW, while higher damage joint count was negatively associated with mean and minimum JSW (MCPJ 2). Use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was negatively associated with minimum JSW (MCPJ 3) while use of biologic DMARDs (bDMARDs) was positively associated with minimum JSW (MCPJ 2). CONCLUSION: Higher inflammatory burden as reflected by longer disease duration, higher ESR levels, and damage joint count was negatively associated with mean, maximum, and minimum JSW, while suppression of inflammation using bDMARDs seems to limit the decline in JSW.

Pharmacokinetics of Apixaban Among Peritoneal Dialysis Patients.

Rationale & Objective: The efficacy and safety profile of apixaban remains uncertain in patients receiving peritoneal dialysis (PD) despite increasing use in this population. Accordingly, we assessed the pharmacokinetics of apixaban among patients receiving PD. Study Design: A pharmacokinetics study in a single center. Patients recruited received 1 week of apixaban at 2.5 mg twice a day to reach steady state. Serial blood samples were then taken before and after the last dose for pharmacokinetics analysis of apixaban. Setting & Participants: Ten stable PD patients with atrial fibrillation in an outpatient setting. Analytical Approach/Outcomes: Pharmacokinetic parameters including the area under the concentration-time curve from time 0 to 12 hours after the last dose of apixaban (AUC0-12), peak concentration, trough level, time to peak apixaban concentration, half-life, and drug clearance were analyzed. Results: There was a wide variation in the range of apixaban concentration across the 10 patients. The AUC0-12 for the PD group was significantly higher than those reported previously for hemodialysis patients or healthy individuals. Three patients had a supratherapeutic peak concentration whereas 2 patients had a supratherapeutic trough level as compared with the pharmacokinetic parameter in healthy individuals taking equivalent therapeutic dosage. Limitations: Small sample size with short study duration limits the ability to ascertain the true bleeding risk and to detect any clinical outcomes. Results may be limited to Asian populations only. Conclusions: A proportion of PD patients had supratherapeutic levels even when the reduced dosage 2.5 mg twice a day was used. Given the large interindividual variation in the drug level, therapeutic drug monitoring should be done if available. Otherwise, one should start the drug at reduced doses with caution and with more frequent clinical monitoring for any signs of bleeding.

Safety Profile and Clinical and Virological Outcomes of Nirmatrelvir-Ritonavir Treatment in Patients With Advanced Chronic Kidney Disease and Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir-ritonavir is currently not recommended in patients with an estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2. METHODS: To determine the safety profile and clinical and virological outcomes of nirmatrelvir-ritonavir use at a modified dosage in adults with chronic kidney disease (CKD), a prospective, single-arm, interventional trial recruited patients with eGFR <30 mL/minute/1.73 m2 and on dialysis. Primary outcomes included safety profile, adverse/serious adverse events, and events leading to drug discontinuation. Disease symptoms, virological outcomes by serial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral polymerase chain reaction (PCR) tests, rapid antigen tests, and virological and symptomatic rebound were also recorded. RESULTS: Fifty-nine (69.4%) of the 85 participants had stage 5 CKD and were on dialysis. Eighty (94.1%) completed the full treatment course; 9.4% and 5.9% had adverse and serious adverse events, and these were comparable between those with eGFR < or >30 mL/minute/1.73 m2. The viral load significantly decreased on days 5, 15, and 30 (P < .001 for all), and the reduction was consistent in the subgroup with eGFR <30 mL/minute/1.73 m2. Ten patients had virological rebound, which was transient and asymptomatic. CONCLUSIONS: Among patients with CKD, a modified dose of nirmatrelvir-ritonavir is a well-tolerated therapy in mild COVID-19 as it can effectively suppress the SARS-CoV-2 viral load with a favorable safety profile. Virological and symptomatic rebound, although transient with low infectivity, may occur after treatment. Nirmatrelvir-ritonavir should be considered for use in patients with CKD, including stage 5 CKD on dialysis. Clinical Trials Registration. Clinical Trials.gov; identifier: NCT05624840.

The effect of Dipeptidyl peptidase 4 (DPP-4) inhibitors on hemoglobin level in diabetic kidney disease: A retrospective cohort study.

Anemia typically develops early in the course of diabetic kidney disease (DKD). There are data to show that dipeptidyl-peptidase-4 (DPP-4) inhibitors affect hematopoietic growth factor activity and hemoglobin level. We retrospectively reviewed 443 DKD patients who were started on DDP-4 inhibitor therapy in 2019. Their hemoglobin level at baseline (6-12 months before treatment), pretreatment (0-6 months before treatment), and post-treatment periods (within 6 months after DPP-4 inhibitor), concomitant estimated glomerular filtration rate (eGFR), HbA1c, peripheral blood white cell and platelet counts were reviewed. The severity of kidney failure was classified according to the Kidney Disease: Improving Global Outcomes stages. The hemoglobin level had a small but significant decline from 11.98 ± 2.07 to 11.87 ± 2.12 g/dL from pretreatment to post-treatment period (paired Student t test, P < .0001). From the pre- to post-treatment period, the decline of hemoglobin level was 0.10 ± 0.89 g/dL, which was significantly less than that from baseline to pretreatment period (0.24 ± 0.90 g/dL, P = .0008). The change in hemoglobin level had a positive correlation with the change in HbA1c level (R = 0.218, P < .0001), but did not correlate with the type of DPP-4 inhibitor or pretreatment eGFR. There was no significant change in peripheral blood white cell or platelet count during the same period. DPP-4 inhibitor ameliorates hemoglobin decline in DKD. The effect of DPP-4 inhibitor on hemoglobin is statistically significant but clinically modest, and did not correlate with the concomitant change in kidney function.

Urinary Long Non-Coding RNA Levels as Biomarkers of Lupus Nephritis.

BACKGROUND: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. METHOD: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. RESULTS: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = -0.423, p = 0.018) and ANRIL levels (r = -0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = -0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = -0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). CONCLUSIONS: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis.

Peritoneal dialysis after failed kidney allograft: Comparing patients with and without pd before transplant.

BACKGROUND: The result of published studies on the clinical outcome of peritoneal dialysis (PD) after kidney allograft failure is conflicting. There are also few published data on the outcome of patients who had PD before kidney transplant and then return to PD after allograft failure. METHODS: We reviewed 100 patients who were started on PD after kidney allograft failure between 2001 and 2020 (failed transplant group); 50 of them received PD before transplant. We compared the clinical outcome to 200 new PD patients matched for age, sex, and diabetic status (control group). RESULTS: The patients were followed for 45.8 ± 40.5 months. the 2-year patient survival rate was 83.3% and 87.8% for the failed transplant and control groups, respectively (log rank test, p = 0.2). The corresponding 2-year technique survival rate 66.5% and 71.7% (p = 0.5). The failed transplant and control groups also had similar hospitalization rate and peritonitis rate. In the failed transplant group, there was also no difference in patient survival, technique survival, hospitalization, or peritonitis rate between those with and without PD before transplant. In the failed transplant group, patients who had PD before transplant and then returned to PD after allograft failure had substantial increase in D/P4 (0.585 ± 0.130 to 0.659 ± 0.111, paired t-test, p = 0.032) and MTAC creatinine (7.74 ± 3.68 to 9.73 ± 3.00 ml/min/1.73m2, p = 0.047) from the time before the transplant to the time after PD was resumed after failed allograft. CONCLUSIONS: The clinical outcome of PD patients with a failed kidney allograft is similar to other PD patients. However, patients who have a history of PD before kidney transplant and then return to PD after allograft failure have increased peritoneal transport parameters.