Long-term Kidney Research Articles

Long-term kidney outcomes in survivors of Wilms tumor: a single-center retrospective cohort study.

Several studies have investigated long-term kidney outcomes in survivors of Wilms tumor (WT). However, many have small sample sizes, and there is a wide variation in reported outcomes. The aim of this study is to investigate the long-term kidney outcomes in survivors of WT (S-WT), including those patients considered to be at high risk for poor kidney outcomes, and using updated estimated glomerular filtration rate (eGFR) equations. This was a retrospective chart review of 64 patients treated for WT at a single pediatric center. Patients were off treatment for 5years or more at the time of analysis and were evaluated for decreased kidney function, hypertension, proteinuria, and compensatory hypertrophy of the contralateral kidney. At a median follow-up time of 11.3years off treatment (range 5-22.6) and average age of 16.7years (range 6.5-30), 35 patients had a decreased eGFR (< 90mL/min/1.73 m2), and 2 patients had progressed to chronic kidney disease stage 5. Compensatory hypertrophy was observed in 67% of cases. 41% of patients had elevated clinic blood pressures, with 2 patients on an anti-hypertensive medication. Three of 9 patients had evidence of hypertension on ambulatory blood pressure monitoring. Eight of 37 patients (22%) had proteinuria. Kidney dysfunction is common in S-WT at a young age. This population should be carefully monitored for the development of decreased eGFR, hypertension, and proteinuria as part of their routine survivorship care. This is particularly true for modifiable risk factors of chronic kidney disease progression, such as hypertension and proteinuria.

Comparative renoprotective effectiveness of allopurinol and febuxostat among hyperuricemic patients with preserved kidney function.

Early initiation of xanthine oxidase inhibitors (XOIs) may benefit patients with preserved kidney function. However, a direct comparison between the impact of allopurinol and those of febuxostat on long-term kidney function among this population is lacking. We conducted a retrospective cohort study with a new-user, active-comparator design among patients with eGFR within the reference range and no proteinuria. The primary outcome was a composite incidence of significant eGFR decline (≥ 40% decline from baseline) and all-cause death at 5 years. Adjusted hazard ratios (HRs) were estimated using Cox's proportional hazard models with inverse probability of treatment and censoring weighting. We analyzed 1,142 patients (287 with allopurinol and 855 with febuxostat). The adjusted HRs (95% confidence intervals) for allopurinol initiators compared to febuxostat initiators for the composite outcome at 5 years were 0.84 (0.74-0.95). The cause-specific adjusted HRs for allopurinol initiators relative to febuxostat initiators were 0.82 (0.70-0.94) for significant eGFR decline over 5 years, and 1.08 (0.91-1.24) for all-cause death over 5 years. Allopurinol initiators preserved kidney function better than febuxostat over 5 years. Clinicians should exercise caution not only when prescribing but also when selecting XOIs, even for patients with preserved kidney function.

Conscious Nutrition to Improve Survival Prognosis of Donor Kidney Recipients: A Narrative Review.

Kidney transplantation is the optimal treatment for end-stage chronic kidney disease, increasing survival rates and improving quality of life. Diet affects patient weight and well-being, can trigger certain diseases, and influences post-surgery outcomes. The purpose of the study was to investigate dietary strategies in patients with chronic kidney disease, in early and long-term donor kidney recipients, and to formulate specific nutritional recommendations. For this purpose, a narrative review of the available information in both the Republic of Kazakhstan and the world's scientific literature over the last 10 years was carried out. The following evidence-based resources were used: Scopus, PubMed, Embase, Cochrane Library, and Web of Knowledge. The study provides the latest statistical data on kidney transplantation and risk factors, and a comparative analysis between countries. Existing data on basic nutrition and the possibility of using it after transplantation are examined in detail. In addition, the recommendations for daily intake of salt, potassium, sodium, vitamin D, and calcium were analyzed. The energy value of the diet and its association with overweight, obesity, and the development of diabetes mellitus were studied. Using DASH (Dietary Approaches to Stop Hypertension) and low-protein diets as examples, the potential risks and their applicability for this patient category are analyzed. The article's materials and conclusions can serve as a training manual for nephrologists, therapists, and surgeons.

Kidney Function Decline After COVID-19 Infection

COVID-19 infection has been associated with acute kidney injury. However, its possible association with long-term kidney function is not well understood. To investigate whether kidney function decline accelerated after COVID-19 compared with after other respiratory tract infections. This cohort study used linked data from the Stockholm Creatinine Measurements (SCREAM) Project between February 1, 2018, and January 1, 2022, in Stockholm, Sweden. All hospitalized and nonhospitalized adults in the database with at least 1 estimated glomerular filtration rate (eGFR) measurement in the 2 years prior to a COVID-19 positive test result or pneumonia diagnosis were selected. Statistical analyses were conducted between June 2023 and October 2024. COVID-19 and pneumonia (including influenza). Mean annual change in eGFR after COVID-19 and after pneumonia was calculated with a linear regression model. The COVID-19 cohort comprised 134 565 individuals (74 819 females [55.6%]; median [IQR] age, 51 [37-64] years). The pneumonia cohort consisted of 35 987 individuals (19 359 females [53.8%]; median [IQR] age, 71 [56-81] years). The median (IQR) baseline eGFR was 94 (79-107) mL/min/1.73m2 for the COVID-19 cohort and 79 (61-92) mL/min/1.73m2 for the pneumonia cohort. After adjustment for covariates, both infections demonstrated accelerated annual eGFR decline, with greater magnitude of decline after COVID-19 (3.4% [95% CI, 3.2%-3.5%] after COVID-19; 2.3% [95% CI, 2.1%-2.5%] after pneumonia). This decline was more severe among individuals hospitalized for COVID-19 (5.4%; 95% CI, 5.2%-5.6%) but remained similar among those hospitalized for pneumonia. This cohort study found an association between COVID-19 and accelerated decline in kidney function, particularly after hospitalization, compared with pneumonia. People who were hospitalized for COVID-19 should receive closer monitoring of kidney function to ensure early diagnosis and optimized management of chronic kidney disease to effectively prevent complications and further decline.

Gestational Exposure to Nonsteroidal Anti-Inflammatory Drugs and Risk of Chronic Kidney Disease in Childhood

Gestational exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of adverse fetal kidney outcomes. However, details regarding timing, specific NSAIDs, and long-term childhood kidney outcomes are limited. To evaluate the association between gestational exposure to NSAIDs and the risk of chronic kidney disease (CKD) in childhood. This national cohort study assessed 1 025 255 children born alive in Taiwan from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2021. Children without valid maternal-child linkage and with incomplete birth information were excluded. Data analysis was performed from November 30, 2023, to April 30, 2024. Maternal prescriptions for NSAIDs from the last menstrual period to birth. The main outcome was childhood CKD, including congenital anomalies of the kidney and urinary tract and other kidney diseases. Cox proportional hazards regression models with stabilized inverse probability of treatment weighting (weighted hazard ratio [wHR]) and a robust sandwich estimator were used to estimate the relative risk of NSAID exposure in pregnancy, adjusted for newborn characteristics. This study included 163 516 singleton-born children (24.0%) whose mothers (mean [SD] age at birth of child, 31.25 [4.92] years) used at least 1 dispensing of an NSAID during pregnancy. Gestational NSAID exposure was significantly associated with a higher risk of childhood CKD (wHR, 1.10; 95% CI, 1.05-1.15). No association was observed between NSAID use and fetal nephrotoxicity in sibling comparisons. Elevated risks were revealed for exposure during the second trimester (wHR, 1.19; 95% CI, 1.11-1.28) and the third trimester (wHR, 1.12; 95% CI, 1.03-1.22) in singleton-born children. Specific NSAID exposures associated with higher CKD risk included indomethacin (wHR, 1.69; 95% CI, 1.10-2.60) and ketorolac (wHR, 1.28; 95% CI, 1.01-1.62) in the first trimester, diclofenac (wHR, 1.27; 95% CI, 1.13-1.42) and mefenamic acid (wHR, 1.29; 95% CI, 1.15-1.46) in the second trimester, and ibuprofen (wHR, 1.34; 95% CI, 1.07-1.68) in the third trimester. In this study, gestational exposure to NSAIDs was not associated with a substantial increase in the risk of childhood CKD when comparing between siblings. However, the findings underscore the need for caution when prescribing NSAIDs during pregnancy, particularly indomethacin and ketorolac in the first trimester, mefenamic acid and diclofenac in the second trimester, and ibuprofen in the third trimester, to ensure the safety of the offspring's kidneys.

Biomarker Panels for Predicting Progression of Kidney Disease in Acute Kidney Injury Survivors.

Acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD). We aimed to identify combinations of clinical variables and biomarkers that predict long-term kidney disease risk after AKI. We analyzed data from a prospective cohort of 723 hospitalized patients with AKI in the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) Study. Using machine learning, we investigated 75 candidate predictors including biomarkers measured at three-month post-discharge follow-up to predict major adverse kidney events (MAKE) within three years, defined as a decline in eGFR ≥40%, development of end-stage kidney disease (ESKD), or death. The mean age of study participants was 64 ± 13 years, 68% were men, and 79% were of White race. Two hundred and four (28%) patients developed MAKE over 3 years of follow-up. Random forest and LASSO penalized regression models using all 75 predictors yielded area under the receiver-operating characteristic curve (AUC) values of 0.80 (95% CI: 0.69-0.91) and 0.79 (95% CI: 0.68-0.90) respectively. The most consistently selected predictors were albuminuria, soluble tumor necrosis factor receptor 1 (sTNFR1), and diuretic use. A parsimonious model using the top eight predictor variables showed similarly strong discrimination for MAKE (AUC = 0.78; 95% CI: 0.66-0.90). Clinical impact utility analyses demonstrated that the eight-predictor model would have 55% higher efficiency of post-AKI care (number needed to screen/follow-up for a MAKE event decreased from 3.55 to 1.97). For a kidney-specific outcome of eGFR decline or ESKD, a four-predictor model showed strong discrimination (AUC = 0.82; 95% CI: 0.68-0.96). Combining clinical data and biomarkers can accurately identify high-risk AKI patients, enabling personalized post-AKI care and improved outcomes.

Kidney Outcomes in Children Receiving Extracorporeal Membrane Oxygenation: A Single-Center Acute Cohort From 2009 to 2019, Followed to 2021.

Long-term kidney outcomes after extracorporeal membrane oxygenation (ECMO) are little quantified and understood. We aimed to describe the frequency of kidney dysfunction screening during follow-up and the prevalence of long-term kidney disease. Retrospective cohort of pediatric ECMO patients with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) using all post-discharge serum creatinine values to define three kidney outcomes: 1) acute kidney injury (AKI), with eGFR of less than 60 mL/min/1.73 m2, which subsequently improved to normal (≥ 90 mL/min/1.73 m2); 2) abnormal eGFR of less than 90 mL/min/1.73 m2 at last follow-up; and 3) chronic kidney disease (CKD) with eGFR of less than 90 mL/min/1.73 m2 on at least two occasions separated by greater than or equal to 90 days, without an intervening or subsequently normal eGFR. Single-center tertiary care children's hospital system. All pediatric patients surviving ECMO from 2009 to 2019. None. In the 10-year cohort of 666 patients, 399 (60%) survived at least 3 months post-discharge. Of these, 382 of 399 (96%) were followed at our institution for a median of 5 years (interquartile range, 3-8 yr). Two hundred sixty-four of 382 (69%) had at least one creatinine value post-discharge, and 209 of 382 (55%) had at least two values three months apart. Of the 264 with at least one creatinine value, 61 (23%) had an abnormal eGFR; of the 209 with at least two values greater than or equal to 90 days apart, 18 (9%) met criteria for CKD. Of those with CKD, 12 of 18 had AKI during ECMO, and seven of 18 had AKI events post-discharge (range, 1-6 episodes). This 2009-2019 pediatric ECMO cohort of survivors, followed for a median of 5 years, shows the subsequent high burden of kidney disease. We found that monitoring and following kidney function was not complete in this population, which is a concern since the rate of later AKI events and CKD is significant. Further study is needed to mitigate this post-ECMO vulnerability.

Sodium‐glucose co‐transporter protein 2 inhibitors for long-term kidney function preservation in type 2 diabetes with chronic kidney disease: a meta-analysis of rates of progression to end-stage renal disease

Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2DM) and a leading cause of end-stage renal disease (ESRD). Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated renoprotective effects in clinical trials, but their precise impact on ESRD risk remains to be comprehensively quantified. This study aimed to evaluate the effectiveness of SGLT2 inhibitors in reducing ESRD risk in T2DM patients with CKD by synthesizing evidence from randomized controlled trials. A meta-analysis was conducted using data from eight randomized controlled trials involving 28,253 participants. Studies comparing SGLT2 inhibitors with placebo in T2DM patients with CKD were included. The primary outcome was the risk of ESRD, reported as a pooled risk ratio (RR) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. The pooled analysis demonstrated a significant reduction in ESRD risk with SGLT2 inhibitors compared to placebo (RR, 0.73; 95% CI, 0.66–0.82), indicating a 27% risk reduction. Heterogeneity was low (I²=0%; p=0.50), confirming consistency across trials. Subgroup analyses showed similar reductions across different CKD stages and follow-up durations. In conclusion, SGLT2 inhibitors significantly reduce the risk of ESRD in T2DM patients with CKD, highlighting their renoprotective potential. These findings support the integration of SGLT2 inhibitors into standard care for high-risk populations to delay CKD progression and prevent ESRD.

The association between TNF-receptors (TNFR1 and TNFR2) and mortality as well as kidney function decline in patients with chronic kidney disease.

Higher circulating levels of tumor necrosis factor (TNF) alpha receptors 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. To study associations between levels of TNFR1 and TNFR2 and all-cause mortality as well as estimated glomerular filtration rate (eGFR) decline. Patients with chronic kidney disease (CKD) stages 3-5 in the Salford Kidney Study were included. Associations between one standard deviation increase in plasma TNFR1 and TNFR2 and mortality were estimated by Cox regression models with hazard ratios (HRs) and 95% confidence intervals adjusted for age, sex, eGFR based on creatinine and cystatin C, urine-protein, C-reactive protin, cardiovascular comorbidity, smoking habits, and diabetes. Differences in eGFR decline in relation to plasma TNFR1 and TNFR2 were estimated by both linear and logistic regression models, with regression coefficients and odds ratios (ORs). Univariate models showed significant associations between TNFR1 (n = 985) and TNFR2 (n = 988) and all-cause mortality based on 7424 person-years at risk, but in the fully adjusted models with continuous variables significant only for TNFR2 HR 1.17 (1.03-1.34), but with a borderline value for TNFR1 HR 1.15 (1.00-1.31). For rapid decliners, that is, eGFR decline in highest TNFR-receptor quartile versus quartiles 1-3, the decline was 1.60% per month (interval 0.78-10.99). For eGFR decline in continuous models, the fully adjusted ORs were for TNFR1 1.29 (0.92-1.81) and for TNFR2 1.33 (0.90-1.98). TNFR2 was associated with mortality, but TNFR1 was not, although showing a borderline value. Neither TNFR1 nor TNFR2 predicted decline in kidney function. TNFR1 and TNFR2 portray interesting aspects in patients with CKD, but the clinical utility seems limited.

Kidney hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in diabetes: physiology and clinical implications

Abstract The progressive loss of kidney function in diabetes mellitus is partly attributable to the occurrence of glomerular hyperfiltration. Consequently, therapeutic interventions that lower intra-glomerular pressure are a cornerstone of treatment in diabetic kidney disease. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce glomerular filtration rate (GFR) and calculated intraglomerular pressures across studies. However, the net effect on arteriolar tone that leads to acute GFR declines may differ between cohorts. While pre-glomerular vasoconstriction appears to be the dominant mechanism responsible for GFR dipping in patients with type 1 diabetes (T1D) and glomerular hyperfiltration, other factors, including postglomerular vasodilation, may contribute to the acute GFR decline in normofilterering individuals with T1D and type 2 diabetes. Regardless of the responsible mechanisms, acute changes in GFR are associated with long-term kidney function preservation—a relationship that may reflect an underlying protective decline in glomerular hypertension.

Association between urinary heavy metal/trace element concentrations and kidney function: a prospective study

Abstract Background Chronic kidney disease (CKD) is an important public health problem. Although cross-sectional studies have identified many heavy metals/trace elements associated with reduced kidney function, prospective studies are needed to determine the pathogenic role of these elements in the development and progression of CKD. Methods To explore the association between baseline urinary heavy metal/trace element concentrations and long-term impaired kidney function (IKF)/CKD, as well as the incidence of rapid decline in kidney function in a population-based exploratory prospective study, we mean age 51.9 years at baseline) whose urinary trace elements concentrations have been determined by inductively coupled plasma mass spectrometry (ICP-MS). IKF was defined by a reduced estimated glomerular filtration rate (eGFR) between 60-90 mL/min/1.73 m2, and CKD was defined as an eGFR&amp;lt;60 mL/min/1.73 m2. Rapid eGFR decline was defined as a decrease≥3 mL/min/1.73 m2 /year. Results Over a mean follow-up of 12.5 years, 123 participants (2.6%) experienced rapid decline in kidney function, and 1455 (31.7%) developed IKF or CKD. After adjusting for covariates including baseline eGFR, we found that urinary vanadium (HR=1.07, 1.03-1.12), cobalt (HR=1.69, 1.21-2.37), nickel (HR=1.19, 1.08-1.3), copper (HR=1.03, 1.01-1.06), selenium (HR=1.33, 1.02-1.73), molybdenum (HR=1.48, 1.2-1.82) and iodine (HR=1.1, 1.02-1.2) were associated with an increased risk of new incident IKF or CKD cases during the follow-up. Also, urinary copper (OR=1.12, 1.04-1.21), silver (OR=1.83, 1-3.35), molybdenum (OR=1.02, 1.01-1.04) and cadmium (OR=1.05, 1.01-1.09) were associated with an increased risk of rapid eGFR decline. Conclusion In the general population, several urinary heavy metals/trace elements are associated with a rapid decline in kidney function or new cases of IKF/CKD.

Albuminuria after Induction Treatment and Kidney Prognosis in ANCA-associated Glomerulonephritis

Abstract Introduction It remains unclear whether persisting proteinuria in ANCA-associated glomerulonephritis (AAGN) reflects damage from the initial injury or ongoing inflammation. Methods A retrospective, single-centre study of biopsy-proven AAGN. The study defines the “albuminuria” group as urine albumin-to-creatinine ratio (ACR) greater than 300 mg/g and the “no albuminuria” group as ACR less than or equal to 300 mg/g at 6 months. We sought the clinical and histopathological characteristics of both the initial and subsequent biopsies and long-term kidney outcomes stratified by albuminuria levels. Results 218 patients were included. Within the first six months, 28 (13%) died or progressed to end-stage kidney disease (ESKD). Among the remaining 190 patients, 37% had an ACR&amp;gt; 300 mg/g at 6 months. The albuminuria group more frequently presented with a Berden mixed or crescentic class and had higher glomerular activity on the initial biopsy. They were more often male (odds ratio [OR] 2.75; 95% CI 1.15-6.54), younger age (OR 0.96; 95% CI, 0.93 to 0.99) and had fewer normal glomeruli in the biopsy (OR 0.96; 95% CI, 0.93 to 0.99) compared to the group without albuminuria. Over the initial 5-year period, the recovery in glomerular filtration rate (eGFR) was lower in the albuminuria group (adjusted mean difference in delta eGFR -12.5 ml/min per 1.73m2; 95% CI, -15.8 to -9.1). In multivariable analysis, ACR greater than 300 mg/g was associated with a higher risk of ESKD, even after adjusting for Berden classification and eGFR at diagnosis (Hazard ratio 6.53; 95% CI, 1.49 to 28.50). Conclusions In a well-defined cohort of AAGN, one-third of the patients, primarily younger males with a lower percentage of normal glomeruli, had persisting albuminuria after induction treatment which was associated with worse kidney outcomes independent of Berden class and eGFR at diagnosis.

A Prospective Study of Nephrocalcinosis in Very Preterm Infants: Incidence, Risk Factors and Vitamin D Intake in the First Month.

Background and objectives: Nephrocalcinosis (NC) is a common condition characterized by the deposition of calcium salts in the kidneys of very preterm infants due to tubular immaturity, intensive treatment and nutritional supplements. However, optimal vitamin D supplementation remains unclear. In most patients, NC spontaneously resolves within the first year of life, but long-term kidney function data are lacking. The aim was to study nephrocalcinosis in very preterm infants, assess risk factors and evaluate vitamin D's impact during the first month with a 2-year follow-up. Material and Methods: This was a prospective observational study conducted over a 3-year period in infants with a gestational age of less than 32 weeks. The patients' data were compared between the NC and control groups based on kidney ultrasound results at discharge. In the first month, the mean vitamin D intake from all sources as well as biochemical markers of calcium metabolism were collected. Patients diagnosed with NC were referred to a pediatric nephrologist after discharge. Results: NC was found in 35% of a cohort of 160 infants, more common in those with a gestational age <28 weeks. Risk factors were associated with higher morbidity and necessary treatment. At 28 days, serum 25-hydroxy vitamin D levels differed between NC and control groups (p < 0.05). The NC group with GA ≥ 28 weeks had higher vitamin D intake (p < 0.05), hypercalciuria and calcium/creatinine ratio (p < 0.01) and lower parathyroid hormone levels (p < 0.05). Follow-up showed resolution in 70% at 12 months and 90% at 24 months. Conclusions: The prevalence of NC in very preterm infants is significant, associated with lower maturity and higher morbidity. Careful vitamin D supplementation and biochemical monitoring of Ca metabolism from the first month of life should support bone health and limit the risk of nephrocalcinosis. Due to the high incidence of NC in very preterm infants, long-term follow-up is essential.

Lower prognostic nutritional index is associated with a greater decline in long-term kidney function in general population

BackgroundThe prognostic nutritional index (PNI) is an integrated index of serum albumin and peripheral lymphocyte count, where low values may reflect poor nutritional status or inflammation. The long-term effect of PNI on renal function is not well known in the general population. Therefore, we investigated whether the PNI is related to renal function changes in the general population.MethodsData from participants who underwent a health check-up between 2002 and 2018 were retrospectively examined. PNI was computed by 10×serum albumin (g/dL) + 0.005×total lymphocyte count (per mm3). The primary exposure was PNI, divided into quintiles. The primary outcome was a 25% decline in eGFR from baseline over a 5-year follow-up period.ResultsThis study included 15,437 participants (mean [standard deviation, SD] age, 43.7 [7.9] years; 46% male). The median (interquartile ranges) 5-year change of eGFR was − 5.2 (− 18.8, − 3.3) mL/min/1.73m2. A total of 2,272 participants (14.7%) experienced a 25% decline in eGFR at 5 years. Compared to the highest PNI group, lower PNI groups were at greater risk for a 25% decline in eGFR; odds ratios and 95% confidence intervals were 1.42 (1.20, 1.68), 1.23 (1.04, 1.45), 1.21 (1.03, 1.43), and 1.19 (1.01, 1.40) for the first to fourth quintiles of PNI, respectively. In linear regression analyses, lower PNI groups also showed a larger decline in eGFR over 5 years compared to the highest PNI group.ConclusionsLower PNI was associated with a larger decline in renal function in the general population.

Predictive utility of nomogram based on serum glucose-regulated protein 78 and kidney function for long-term kidney graft survival

The estimated glomerular filtration rate (eGFR) at 1 year post-transplantation is a well-established predictor of long-term graft survival; however, its predictive accuracy needs improvement. We retrospectively analyzed data from 51 kidney transplant recipients at Kanazawa Medical University Hospital (January 2001–February 2015). Cox regression was used to identify risk factors for death-censored graft loss and create a nomogram to predict graft survival at 15 years post-transplantation. The predictive factors ultimately included in the nomogram included eGFR and serum glucose-regulated protein 78 (GRP78) at 1 year post-transplantation. In terms of discrimination, assessed by area under the receiver operating characteristic curve (AUC-ROC), no significant difference was noted between the eGFR model (AUC 0.84 [0.67–1.00]) and nomogram (AUC 0.92 [0.82–1.00]) (p = 0.38). However, calibration, evaluated by the calibration plot, indicated superiority of the nomogram over the eGFR model, confirmed in the internal validation cohort using the Bootstrap method. Regarding clinical value evaluated by decision curve analysis, the nomogram showed a greater net benefit than the eGFR model, especially at wider diagnostic thresholds (particularly important lower thresholds). Our findings suggest the added predictive value of serum GRP78 at 1 year post-transplantation for long-term graft survival prediction.

Long-term outcomes of IgA nephropathy in China.

The long-term prognosis of IgA nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission. We enrolled 2 141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression, and an eGFR slope calculated via a linear mixed model to investigate kidney outcomes. The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/d, and the estimated GFR was 80 (52, 103) mL/min/1.73m2. After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years, and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted HR: 1.76, 95%CI: 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5g/d. There was no significant difference in long-term kidney survival between patients with proteinuria<0.3g/d and those with 0.3-0.5g/d, with both groups demonstrating a better prognosis. The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria≥0.5g/d experience worse kidney outcomes, challenging the previous view that proteinuria<1.0g/d was associated with a low risk of kidney failure.

Graft-derived cell free DNA: used for assessment of early graft status and its implications for long-term kidney function.

The long-term graft survival is closely related to its early status, yet the indices for assessing the early graft status are complex and lack quantitative values. The aim of this study is to investigate the potential of GcfDNA as a comprehensive, non-invasive, convenient, and quantifiable indicator for evaluating early graft status. In this study, 138 recipients who underwent primary kidney transplantation were enrolled. Peripheral blood samples, each 10 mL, were collected on days 1 and 7 post-transplantation. The quantification of both the graft cell-free DNA (GcfDNA) fraction (%) and GcfDNA concentration (copies per milliliter, cp/mL) was performed using droplet digital PCR (ddPCR). For most recipients, both the GcfDNA fraction and concentration had a rapid decline at 7 days post-transplantation, reaching median values of approximately 0.7% and 53.5 cp/mL, respectively. No significant associations were found between GcfDNA values and other clinical parameters. On the seventh postoperative day, we observed a significant elevation in GcfDNA concentration among recipients with eGFR values < 60 mL/min/1.73 m2. Additionally, notable increases were identified in both GcfDNA fraction and concentration variations within this specific subgroup. The findings of our study indicate a negative correlation between the concentration and fractional changes of GcfDNA on postoperative days 1 and 7, as well as the GcfDNA concentration on postoperative day 7, with eGFR within the 1-2 years post-transplantation period. The ROC curve of GcfDNA_Copies_Variation. day1-day 7 showed the highest AUC value AUC = 0.8006, with high sensitivity (90.14%) and specificity (77.61%), and PPV and NPV were 81.01% and 88.14%, respectively. Using four classical algorithm models, we found that the xgboost regression model achieved the best predictive performance (area under the curve (AUC) values = 0.862) for eGFR within 1-2 years post-transplantation, with high sensitivity (85.7%) and specificity (85%). The changes of GcfDNA levels in the early stage are closely related to kidney function within 1-2 years post-transplantation. As a comprehensive indicator of graft function, GcfDNA has great potential for clinical application.

The Use of Machine Learning in the Diagnosis of Kidney Allograft Rejection: Current Knowledge and Applications.

Kidney allograft rejection is one of the main limitations to long-term kidney transplant survival. The diagnostic gold standard for detecting rejection is a kidney biopsy, an invasive procedure that can often give imprecise results due to complex diagnostic criteria and high interobserver variability. In recent years, several additional diagnostic approaches to rejection have been investigated, some of them with the aid of machine learning (ML). In this review, we addressed studies that investigated the detection of kidney allograft rejection over the last decade using various ML algorithms. Various ML techniques were used in three main categories: (a) histopathologic assessment of kidney tissue with the aim to improve the diagnostic accuracy of a kidney biopsy, (b) assessment of gene expression in rejected kidney tissue or peripheral blood and the development of diagnostic classifiers based on these data, (c) radiologic assessment of kidney tissue using diffusion-weighted magnetic resonance imaging and the construction of a computer-aided diagnostic system. In histopathology, ML algorithms could serve as a support to the pathologist to avoid misclassifications and overcome interobserver variability. Diagnostic platforms based on biopsy-based transcripts serve as a supplement to a kidney biopsy, especially in cases where histopathologic diagnosis is inconclusive. ML models based on radiologic evaluation or gene signature in peripheral blood may be useful in cases where kidney biopsy is contraindicated in addition to other non-invasive biomarkers. The implementation of ML-based diagnostic methods is usually slow and undertaken with caution considering ethical and legal issues. In summary, the approach to the diagnosis of rejection should be individualized and based on all available diagnostic tools (including ML-based), leaving the responsibility for over- and under-treatment in the hands of the clinician.

Kidney disease and reproductive health.

Understanding the relationship between reproductive health and kidney function is important to provide holistic care for people living with kidney disease. Chronic kidney disease (CKD) has negative impacts on both male and female fertility owing to factors including inflammation, hormonal dysregulation, reduced ovarian reserve, reduced sperm quality and sexual dysfunction. However, pregnancy is achievable for most cisgender women with kidney disease, including kidney transplant recipients and patients on dialysis. CKD in pregnancy is associated with health risks to the mother and child, including increased risk of progression of kidney disease, hypertensive complications of pregnancy, and neonatal complications including fetal growth restriction, preterm birth and stillbirth. However, with appropriate pre-pregnancy counselling, fertility assessment and support, health optimization, and evidence-based antenatal care, the majority of patients will achieve a good outcome. Medication safety should be reviewed before and during pregnancy and lactation, weighing the risk of disease flare against potential adverse effects on the offspring. Important areas for further research include the optimal timing of delivery and the short- and long-term cardiovascular and renal impacts of pregnancy in patients with CKD, as well as long-term kidney and cardiovascular outcomes in their offspring.

Surrogate End Points in Apolipoprotein L1 - Associated Kidney Disease : Evaluation in Three Cohorts.

Surrogate endpoints for the clinical outcome of kidney failure have been accepted by the United States Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 (APOL1)-associated kidney disease. This random-effects meta-analysis included African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (N=3071), the Chronic Renal Insufficiency Cohort (CRIC; N=998), and the African American Study of Kidney Disease and Hypertension (AASK; N=609). Surrogate endpoints included three-year 30% and 40% decline in glomerular filtration rate (GFR), doubling of urine protein-to-creatinine ratio (UPCR), and >3 ml/min/1.73 m2 per year decline in GFR. Clinical outcomes included kidney failure requiring kidney replacement therapy, heart failure, cardiovascular disease, and death after three years.Results: 22% in AASK, 18% in CRIC, and 13% in ARIC had the APOL1 high risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all three-year GFR outcomes but not doubling of UPCR, as well as kidney failure after three years. The three-year outcomes were strongly associated with kidney failure, with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status. Individuals with the APOL1 high risk genotype were more susceptible to three-year GFR-related endpoints and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term-clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1-associated kidney disease.