Higher Risk Of Kidney Failure Research Articles

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease.

Chronic kidney disease (CKD) impacts 14% of adults in the United States, and African American (AA) individuals are disproportionately affected, with more than 3 times higher risk of kidney failure as compared to White individuals. This study evaluated the effects of base-producing fruit and vegetables (FVs) on cardiorenal outcomes in AA persons with CKD and hypertension (HTN) in a low socioeconomic area. The "Cardiorenal Protective Diet" prospective randomized trial evaluated the effects of a 6-week, community-based FV intervention compared to a waitlist control (WL) in 91 AA adults (age = 58.3 ± 10.1 years, 66% female, 48% income ≤ USD 25K). Biometric and metabolomic variables were collected at baseline and 6 weeks post-intervention. The change in health outcomes for both groups was statistically insignificant (p > 0.05), though small reductions in albumin to creatinine ratio, body mass index, total cholesterol, and systolic blood pressure were observed in the FV group. Metabolomic profiling identified key markers (p < 0.05), including C3, C5, 1-Met-His, kynurenine, PC ae 38:5, and choline, indicating kidney function decline in the WL group. Overall, delivering a directed cardiorenal protective diet intervention improved cardiorenal outcomes in AA adults with CKD and HTN. Additionally, metabolomic profiling may serve as a prognostic technique for the early identification of biomarkers as indicators for worsening CKD and increased CVD risk.

Magnetic quaternary ammonium polymer bearing porous agarose for selective extraction of Aristolochic acids in the plasma

Aristolochic acids (AAs) naturally occurring in the herbal genus Aristolochia are associated with a high risk of kidney failure, multiple tumors and cancers. However, approaches with high selectivity and rapidity for measuring AAs in biological samples are still inadequate. Inspired by the mechanism of AAs-induced nephrotoxicity, we designed a hybrid magnetic polymer-porous agarose (denoted as MNs@SiO2M@DNV-A), mimicking the effect of basic and aromatic residues of organic anion transporter 1 (OAT1) for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in the plasma. The monomers of vinylbenzyl trimethylammonium chloride (VBTAC), N-vinyl-2-pyrrolidinone (NVP) and divinylbenzene (DVB) were employed to construct the polymer layer, which provided a selective adsorption for AAs by multiple interactions. The porous agarose shell contributed to remove interfering proteins in the plasma samples. A magnetic solid-phase extraction (MSPE) based on the proposed composite enhanced the selectivity toward AA I and AA II in the plasma samples. In combination of HPLC analysis, the proposed method was proved to be applicable to fast and specific quantification of AAs in blood samples, which was characterized by a good linearity, high sensitivity, acceptable recovery, excellent repeatability and satisfactory reusability.

Haemoglobin, albumin, lymphocyte, and platelet score as an independent predictor for renal prognosis in IgA nephropathy.

The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN). This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC). A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002). HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

499 Physiological and Metabolomic Effects of a Community-Based Cardiorenal Protective Diet Intervention in African Americans with Chronic Kidney Disease and Hypertension

OBJECTIVES/GOALS: Chronic kidney disease (CKD) impacts 15% of US adults and African American (AA) persons are disproportionately affected with more than 3 times higher risk of kidney failure when compared to Caucasian persons. This study evaluated the physiological and metabolomic effects of increased fruits and vegetables (F&amp;V) on cardio-renal risk factors. METHODS/STUDY POPULATION: This pilot trial used a prospective, 2-group, randomized study design to evaluate a F&amp;V intervention (N=46), where participants received a prescribed amount of fresh, base-producing F&amp;V compared to a wait-list control (WL) condition (N=45). All participants were African American adults (≥18 years), had self-reported hypertension, and had CKD (Stage 1-3) on screening spot-urine microalbumin test. Participants were measured at baseline and 6 weeks post-intervention. Clinical data (i.e., systolic and diastolic blood pressure, lipid panel, hemoglobin A1C, BMI [body mass index], and albumin to creatinine ratio) were collected. Targeted metabolomic quantitative analysis was performed followed by LC-MS/MS and FIA-MS/MS. Linear mixed models evaluated analyte expression and clinical data. RESULTS/ANTICIPATED RESULTS: AA participants (N=91) were aged 58 ± 10.2 years, 66% female, and 54% had incomes ≤$50,000. T-tests compared change scores (baseline to 6-weeks) between groups. The F&amp;V group demonstrated a significant reduction in BMI of -4.7 ± 10.5 kg/m² compared to a 1.9 ± 8.3 kg/m² increase in the WL group, p&lt;.01. Further, the F&amp;V group demonstrated a reduction in total cholesterol of -15.4 ± 58.8 mg/dL compared to a 17.7 ± 68.8 mg/dL increase in the WL group, p&lt;.05. Non-significant reductions in hemoglobin A1c were found in the F&amp;V versus the WL group. Metabolomic analysis indicated significant variation with an increase of suggestive key biomarkers for worse CKD in the WL versus F&amp;V groups at 6-weeks. DISCUSSION/SIGNIFICANCE: Consumption of only 2 cups of F&amp;V via a community-based intervention reduced CVD risk factors in AA adults with CKD and HTN and resulted in molecular/biochemical changes which may improve long-term kidney health. Further investigation may lead to development of cost-effective dietary intervention models to improve CKD outcomes in AA persons.

Association between urinary uric acid excretion and kidney outcome in patients with CKD

Inhibiting tubular urate reabsorption may protect the kidney from urate-induced tubular injury. However, this approach may promote intratubular uric acid crystallization, especially in acidified urine, which could be toxic to the kidney. To assess how tubular urate handling affects kidney outcomes, we conducted a retrospective cohort study including 1042 patients with estimated glomerular filtration rates (eGFR) of 15–60 mL/min/1.73 m2. The exposures were fractional excretion of uric acid (FEUA) and urinary uric acid-to-creatinine ratio (UUCR). The kidney outcome was defined as a halving of eGFR from baseline or initiating kidney replacement therapy. The median FEUA and UUCR were 7.2% and 0.33 g/gCre, respectively. During a median follow-up of 1.9 years, 314 kidney outcomes occurred. In a multivariate Cox model, the lowest FEUA quartile exhibited a 1.68-fold higher rate of kidney outcome than the highest FEUA quartile (95% confidence interval, 1.13–2.50; P = 0.01). Similarly, lower UUCR was associated with a higher rate of kidney outcome. Notably, patients in the highest quartile of FEUA and UUCR were at the lowest risk of kidney outcome even among those with aciduria. In conclusion, lower FEUA and UUCR were associated with a higher risk of kidney failure, suggesting that increased urate reabsorption is harmful to the kidney.

Variations in Incidence and Prognosis of Stage 4 CKD Among Adults Identified Using Different Algorithms: A Population-Based Cohort Study

Rationale & ObjectiveClinical guidelines define chronic kidney disease (CKD) as abnormalities of kidney structure or function for >3 months. Assessment of the duration criterion may be implemented in different ways, potentially impacting estimates of disease incidence or prevalence in the population, individual diagnosis, and treatment decisions, especially for more severe cases. We investigated differences in incidence and prognosis of CKD G4 identified by one of four algorithms. Study DesignPopulation-based cohort study in Alberta, Canada. Setting & ParticipantsResidents >18 years old with incident CKD G4 (eGFR 15-29 mL/min/1.73 m2) diagnosed between April 1, 2015 and March 31, 2018, based on administrative and laboratory data. ExposuresFour outpatient eGFR-based algorithms, increasing in stringency, for defining cohorts with CKD G4 were evaluated: (1) a single test, (2) first eGFR <30 mL/min/1.73 m2 and a second eGFR 15-29 mL/min/1.73 m2 >90 days apart (two tests), (3) ≥2 eGFR measurements <30 mL/min/1.73 m2 sustained for >90 days (qualifying period) and the last eGFR in the qualifying period of 15-29 mL/min/1.73 m2 (relaxed sustained), (4) ≥2 consecutive measurements 15-29 mL/min/1.73 m2 for >90 days (rigorous sustained). OutcomesTime to the earliest of death, eGFR improvement (a sustained increase in eGFR to ≥30 mL/min/1.73 m2 for >90 days and >25% increase from the index eGFR), or kidney failure. Analytical ApproachFor each of the 4 cohorts, incidence rates and event-specific cumulative incidence functions at 1 year from cohort entry were estimated. ResultsThe incidence rates of CKD G4 decreased as algorithms became more stringent, from 190.7 (single test) to 79.9 (rigorous sustained) per 100,000 person-years. The two cohorts based on sustained reductions in eGFR were of comparable size and 1-year event-specific probabilities. The two cohorts based on a single test and a two-test sequence were larger and experienced higher probabilities of eGFR improvement. LimitationsA short follow-up period of 1 year and a predominantly White population. ConclusionsThe use of more stringent algorithms for defining CKD G4 results in substantially lower estimates of disease incidence, the identification of a group with a lower probability of eGFR improvement, and a higher risk of kidney failure. These findings can inform implementation decisions of disease definitions in clinical reporting systems and research studies.

Targeting complement in IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Recent years have witnessed significant improvements in the understanding of the pathogenesis of IgAN and particularly, the pathogenic role of complement activation. The alternative complement pathway is the major complement cascade activator in IgAN, and glomerular C3 deposition has been shown to correlate with disease progression. In addition, several studies have provided insight into the pathogenic role of factor H-related proteins -1 and -5 in IgAN, as independent players in complement dysregulation. The lectin pathway has also been shown to be associated with the severity of IgAN. Glomerular deposition of C4d has been associated with increased histologic disease activity, faster decline in estimated glomerular filtration rate and higher risk of kidney failure. On the other hand, although overlooked in the Oxford classification, numerous studies have shown that the coexistence of thrombotic microangiopathy in IgAN is a significant indicator of a poorer prognosis. All the breakthroughs in the understanding of the contributing role of complement in IgAN have paved the way for the development of new complement-targeted therapies in this disease. Several ongoing trials are evaluating the efficacy of new agents against factor B (iptacopan, Ionis-FB-LRX), C3 (pegcetacoplan), factor D (vemircopan, pelecopan), C5 (ravulizumab, cemdisiran) and C5a receptor 1 (avacopan). In this study, we provide a comprehensive review of the role of complement in IgAN, including the emerging mechanisms of complement activation and the promising potential of complement inhibitors as a viable treatment option for IgAN.

Monoclonal Gammopathy and Its Association with Progression to Kidney Failure and Mortality in Patients with CKD.

Little is known about the prognostic significance of monoclonal gammopathy of undetermined and renal significance (MGUS and MGRS) in patients with CKD. The objective of this study was to determine the clinical and kidney outcomes of patients with CKD with either MGUS or MGRS compared with those with CKD without MGUS or MGRS. We conducted a retrospective cohort study from 2013 to 2018. Patients who had both CKD diagnosis and monoclonal testing were identified. Patients were divided into MGRS, MGUS, and no monoclonal gammopathy groups. Cumulative incidence functions and Cox proportional hazards regression were used to model time to event data and to evaluate the association between monoclonal gammopathy status and risk of kidney failure, with death treated as a competing risk. Among 1535 patients, 59 (4%) had MGRS, 648 (42%) had MGUS, and 828 (54%) had no monoclonal gammopathy. Unadjusted analysis showed that compared with no monoclonal gammopathy patients, patients with MGRS were at higher risk of kidney failure (hazard ratio [HR] [95% confidence interval]: 2.5 [1.5 to 4.2] but not patients with MGUS (HR [95% confidence interval]: 1.3 [0.97 to 1.6]), after taking death into account as a competing risk. However, in the multivariable analysis, after adjusting for age, sex, eGFR, proteinuria, and Charlson Comorbidity Index, the risk of progression to kidney failure (with death as competing risk) in the MGRS group was no longer statistically significant (HR: 0.9 [0.5 to 1.8]). The same was also true for the MGUS group compared with the group with no monoclonal gammopathy (HR: 1.3 [0.95 to 1.6]). When evaluating the association between MGUS/MGRS status and overall survival, MGRS was significantly associated with mortality in fully adjusted models compared with the group with no monoclonal gammopathy, while MGUS was not. After adjusting for traditional risk factors, MGUS/MGRS status was not associated with a greater risk of kidney failure, but MGRS was associated with a higher risk of mortality compared with patients with no monoclonal gammopathy.

Risk of kidney failure in patients with systemic sclerosis: a nationwide population-based study

ObjectiveData from a decade ago have shown that patients with systemic sclerosis (SSc) have a higher risk of kidney failure than the general population. However, as the incidence of kidney...

Differences in Outcomes by Place of Origin among Hispanic Patients with Kidney Failure.

Hispanic patients are known to have a higher risk of kidney failure and lower rates of home dialysis use and kidney transplantation than non-Hispanic White patients. However, it is unknown whether these outcomes differ within the Hispanic community, which is heterogeneous in its members' places of origins. Using United States Renal Data System data, the authors found similar adjusted rates of home dialysis use for patients originating from places outside the United States and US-born Hispanic patients, whereas the adjusted risk of mortality and likelihood of transplantation differed depending on place (country or territory) of origin. Understanding the heterogeneity in kidney disease outcomes and treatment within the Hispanic community is crucial in designing interventions and implementation strategies to ensure that Hispanic individuals with kidney failure have equitable access to care. Compared with non-Hispanic White groups, Hispanic individuals have a higher risk of kidney failure yet lower rates of living donor transplantation and home dialysis. However, how home dialysis, mortality, and transplantation vary within the Hispanic community depending on patients' place of origin is unclear. We identified adult Hispanic patients from the United States Renal Data System who initiated dialysis in 2009-2017. Primary exposure was country or territory of origin (the United States, Mexico, US-Puerto Rico, and other countries). We used logistic regression to estimate differences in odds of initiating home dialysis and competing risk models to estimate subdistribution hazard ratios (SHR) of mortality and kidney transplantation. Of 137,039 patients, 44.4% were US-born, 30.9% were from Mexico, 12.9% were from US-Puerto Rico, and 11.8% were from other countries. Home dialysis rates were higher among US-born patients, but not significantly different after adjusting for demographic, medical, socioeconomic, and facility-level factors. Adjusted mortality risk was higher for individuals from US-Puerto Rico (SHR, 1.04; 95% confidence interval [CI], 1.01 to 1.08) and lower for Mexico (SHR, 0.80; 95% CI, 0.78 to 0.81) and other countries (SHR, 0.83; 95% CI, 0.81 to 0.86) compared with US-born patients. The adjusted rate of transplantation for Mexican or US-Puerto Rican patients was similar to that of US-born patients but higher for those from other countries (SHR, 1.22; 95% CI, 1.15 to 1.30). Hispanic people from different places of origin have similar adjusted rates of home dialysis but different adjusted rates of mortality and kidney transplantation. Further research is needed to understand the mechanisms underlying these observed differences in outcomes.

Loss of Glomerular Permselectivity in Type 2 Diabetes Associates With Progression to Kidney Failure.

We examined whether defects in glomerular size selectivity in type 2 diabetes (T2D) associated with progressive kidney disease. Glomerular filtration rate (GFR) and fractional clearances of dextrans of graded sizes were measured in 185 Pima Indians. The permselectivity model that best fit the dextran sieving data represented the glomerular capillary as being perforated by small restrictive pores and a parallel population of larger non-restrictive pores characterized by ωo, the fraction of total filtrate volume passing through this shunt. Hazard ratio (HR) for kidney failure was expressed per 1 standard deviation (SD) increase of ωo by Cox regression after adjusting for age, sex, mean arterial pressure, HbA1c, GFR, and the urine albumin-to-creatinine ratio (ACR). Baseline mean age (±SD) was 43±10 years, HbA1c 8.9±2.5%, GFR 147±46 ml/min, and median (IQR) ACR 41 (11-230) mg/g. During a median follow-up of 17.7 years, 70 participants developed kidney failure. After adjustment, each 1 SD increment in ωo was associated with a higher risk of kidney failure (HR=1.49, 95% CI 1.13, 1.96). Enhanced transglomerular passage of test macromolecules associated with progression to kidney failure, independent of albuminuria and GFR, suggesting that mechanisms associated with impaired glomerular permselectivity are important determinants of progressive kidney disease.

Trends in the Incidence of End-Stage Kidney Disease in Type 1 and Type 2 Diabetes in Australia, 2010-2019

Trends in end-stage kidney disease (ESKD) among people with diabetes may inform clinical management and public health strategies. We estimated trends inthe incidence of ESKD among people with type 1 and type 2 diabetes in Australia from 2010-2019 and evaluated their associated factors. Cohort study. 71,700 people with type 1 and 1,112,690 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS). We estimated the incidence of kidney replacement therapy (KRT) via linkage to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) and the incidence of KRT or death from ESKD by linking the NDSS to the ANZDATA and the National Death Index for Australia. Calendar time, sex, age, and duration of diabetes. Incidence of KRT and KRT or death from ESKD. Incidence of ESKD, trendsover time, and associations with factors related to these trends were modeled using Poisson regression stratified by diabetes type and sex. The median duration of diabetes increased from 15.3 to 16.8 years in type 1 diabetes, and from 7.6 to 10.2 years in type 2 diabetes between 2010 and 2019. The incidence of KRT and KRT or death from ESKD did not significantly change over this time interval among people with type 1 diabetes. Conversely, the age-adjusted incidence of KRT and KRT or death from ESKD increased among males with type 2 diabetes (annual percent changes [APCs]: 2.52% [95% CI, 1.54 to -3.52] and 1.27% [95% CI, 0.53 2.03], respectively), with no significant change among females (0.67% [95% CI,-0.68 to 2.04] and 0.07% [95% CI,-0.81 to 0.96], respectively). After further adjustment for duration of diabetes, the incidence of ESKD fell between 2010 and 2019, with APCs of-0.09% (95% CI,-1.06 to 0.89) and-2.63% (95% CI,-3.96 to-1.27) for KRT and-0.97% (95% CI,-1.71 to-0.23) and-2.75% (95% CI,-3.62 to-1.87) for KRT or death from ESKD among males and females, respectively. NDSS only captures 80%-90% of people with diabetes; lack of clinical covariates limits understanding of trends. While the age-adjusted incidence of ESKD increased for males and was stable for females over the last decade, after adjusting for increases in duration of diabetes the risk of developing ESKD has decreased for both males and females. Previous studies showed an increase in new cases of kidney failure among people with type 2 diabetes, but more recent data have not been available. Here, we report trends in the rate of kidney failure for people with type 2 diabetes from 2010 to 2019 and showed that while more people with type 2 diabetes are developing kidney failure, accounting for the fact that they are also surviving longer (and therefore have a higher chance of kidney failure) the growth in this population is not caused by a higher risk of kidney failure. Nevertheless, more people are getting kidney failure than before, which will impact health care systems for years to come.

Facilitating Medical Care for Latinx Individuals at Risk for CKD: A Pilot Intervention

Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. The objective of this study was to determine the feasibility and acceptability of a community health worker (CHW) intervention that facilitated access to medical care for Latinx individuals. Single-arm prospective study. Latinx adults were found to have albuminuria or risk factors for kidney disease at community screening events in Austin, Texas. A 6-month CHW intervention that facilitated the following: (1) obtaining medical insurance; (2) medical care coordination with primary and nephrology care; (3) kidney disease education; and (4) connection with local resources to address health-related social needs. Recruitment, retention, medical care linkage, and participant and CHW-reported satisfaction with the intervention. Of the 173 individuals who attended the 2 community screening events, 49 agreed to participate in the study, of whom, 51% were men with a mean±standard deviation (SD) age of 45±14 years, and all self-identified as Mexican or Chicano. The mean±SD estimated glomerular filtration rate (eGFR) was 110±21mL/min/1.73m2 and 41% of the participants reported a urine albumin-creatinine ratio of≥30mg/g. Among those enrolled, 28 of the 49 (57%) completed at least 1 CHW visit, and 20 of 49 (41%) completed the intervention. 7 individuals who needed assistance with insurance obtained insurance, and 15 of 20 (75%) scheduled an appointment with a primary care physician within 180 days. Participants reported that the US health care previously seemed inaccessible but gained insurance, the ability to navigate the system, and the ability to help others in their community to access medical care because of the program. Small sample size and a single community may limit generalizability. We reported the acceptability of a CHW intervention. We encountered challenges with feasibility and identified strategies to overcome them. Studies are needed to test the effect of CHW interventions on outcomes and kidney health disparities. National Kidney Foundation young investigator research grant to Dr Novick. Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. We piloted a community health worker intervention that connected people with risk factors or showed evidence of kidney dysfunction at community screening events with medical care. Our findings indicate the acceptability of the intervention. We encountered challenges with feasibility and identified strategies to overcome them.

Renal Histopathology Associated With Kidney Failure and Mortality in Patients With Lupus Nephritis: A Long-Term Real-World Data Study.

Lupus nephritis (LN), a common manifestation of systemic lupus erythematosus, is associated with a higher risk of kidney failure and death. The renal pathology of LN helps elucidate the severity of inflammation and the extent of irreversible damage. We aimed to identify histologic variables that correlate with risks of kidney failure and mortality. Between 2006 and 2019, a total of 526 patients with LN were enrolled. Renal pathology was classified according to the International Society of Nephrology/Renal Pathology Society classification. Components of activity and chronicity indices were analyzed to determine which variables correlated with an increased risk of kidney failure and death, with the adjustment of potential confounders. During the follow-up period (median 7.5, IQR 3.5-10.7 years), 58 patients progressed to kidney failure and 64 died. In the multivariate Cox regression analysis, tubular atrophy (hazard ratio [HR] 2.28, 95% CI 1.66-3.14) and tubulointerstitial inflammation (HR 3.13, 95% CI 1.34-7.33) predicted kidney failure. The renal outcome was even worse if tubular atrophy and tubulointerstitial inflammation coexisted (10-year kidney survival rate: 63.22%). The presence of cellular crescents was associated with an increased risk of death in male patients with LN (HR 1.91, 95% CI 1.02-3.57), whereas the presence of fibrous crescents predicted death in female patients with LN (HR 5.70, 95% CI 1.61-20.25). Histologic variables of renal biopsy in LN could be regarded as prognostic indicators for kidney failure and mortality.

Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, graft versus host disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations, and outcomes. Material and Methods: Out of 2,930 patients who underwent HSCT at our center between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years, and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9–30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy (TMA, 12/19 [63%]) or nephrotic syndrome (NS, 7/19 [37%]) pattern. Glomerular tuft “mesangiolysis” was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the 7 patients with NS pattern, membranous nephropathy was seen in 4 (57%) and minimal change disease in 3 (43%) patients. Thirty-nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy, and were significantly at a higher risk of kidney failure (IS: 2/11, 18.1% vs. no IS: 2/6, 33.3%, p = 0.04). “Associated extra-renal GvHD” occurred in 11/19 (57.9%) allogenic recipients. Patients with “associated extra-renal GvHD” had significantly more deaths (6/11, 60% vs. 0, p = 0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without “associated extra-renal GvHD” after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of IS.

Complex Interventions Across Primary and Secondary Care to Optimize Population Kidney Health: A Systematic Review and Realist Synthesis to Understand Contexts, Mechanisms, and Outcomes.

CKD affects 850 million people worldwide and is associated with high risk of kidney failure and death. Existing, evidence-based treatments are not implemented in at least a third of eligible patients, and there is socioeconomic inequity in access to care. While interventions aiming to improve delivery of evidence-based care exist, these are often complex, with intervention mechanisms acting and interacting in specific contexts to achieve desired outcomes. We undertook realist synthesis to develop a model of these context-mechanism-outcome interactions. We included references from two existing systematic reviews and from database searches. Six reviewers produced a long list of study context-mechanism-outcome configurations based on review of individual studies. During group sessions, these were synthesized to produce an integrated model of intervention mechanisms, how they act and interact to deliver desired outcomes, and in which contexts these mechanisms work. Searches identified 3371 relevant studies, of which 60 were included, most from North America and Europe. Key intervention components included automated detection of higher-risk cases in primary care with management advice to general practitioners, educational support, and non-patient-facing nephrologist review. Where successful, these components promote clinician learning during the process of managing patients with CKD, promote clinician motivation to take steps toward evidence-based CKD management, and integrate dynamically with existing workflows. These mechanisms have the potential to result in improved population kidney disease outcomes and cardiovascular outcomes in supportive contexts (organizational buy-in, compatibility of interventions, geographical considerations). However, patient perspectives were unavailable and therefore did not contribute to our findings. This systematic review and realist synthesis describes how complex interventions work to improve delivery of CKD care, providing a framework within which future interventions can be developed. Included studies provided insight into the functioning of these interventions, but patient perspectives were lacking in available literature. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_05_08_CJN0000000000000136.mp3.

IgA Nephropathy Patient Baseline Characteristics in the Sparsentan PROTECT Study

Sparsentan is a novel single-molecule dual endothelin angiotensin receptor antagonist with hemodynamic and anti-inflammatory properties and is not an immunosuppressant. The ongoing phase 3 PROTECT trial examines sparsentan in adults with IgA nephropathy (IgAN). The PROTECT trial (NCT03762850) is a multicenter, international, randomized, double-blind, parallel-group, active-controlled study. The efficacy and safety of sparsentan versus the active control irbesartan is being evaluated in adults with biopsy-proven IgAN and proteinuria≥1.0 g/d despite maximized treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) for at least 12 weeks. Blinded and aggregated baseline characteristics are reported descriptively and compared to contemporary phase 3 trials with patients with IgAN. The primary analysis population includes 404 patients who were randomized and received study drug (median age, 46 years). Enrolled patients were from Europe (53%), Asia Pacific (27%), and North America (20%). Baseline median urinary protein excretion was 1.8 g/d. The range of estimated glomerular filtration rate (eGFR) was broad with the largest proportion of patients (35%) in chronic kidney disease (CKD) stage 3B. Before transitioning to study medication, mean systolic/diastolic blood pressure was 129/82 mmHg, with the majority of patients (63.4%) receiving the maximum labeled ACEi or ARB dose. Patients in Asian versus non-Asian regions included a higher percentage of females, had lower blood pressures, and included lower proportions of patients with a history of hypertension and baseline antihypertensive treatment. Patient enrollment in PROTECT, with differing racial backgrounds and across CKD stages, will allow for important characterization of the treatment effect of sparsentan in patients with IgAN with proteinuria at high risk of kidney failure.

Clinical and Genetic Characteristics of CKD Patients with High-Risk APOL1 Genotypes.

APOL1 high-risk genotypes confer a significant risk of kidney disease, but variability in patient outcomes suggests the presence of modifiers of the APOL1 effect. We show that a diverse population of CKD patients with high-risk APOL1 genotypes have an increased lifetime risk of kidney failure and higher eGFR decline rates, with a graded risk among specific high-risk genotypes. CKD patients with high-risk APOL1 genotypes have a lower diagnostic yield for monogenic kidney disease. Exome sequencing revealed enrichment of rare missense variants within the inflammasome pathway modifying the effect of APOL1 risk genotypes, which may explain some clinical heterogeneity. APOL1 genotype has significant effects on kidney disease development and progression that vary among specific causes of kidney disease, suggesting the presence of effect modifiers. We assessed the risk of kidney failure and the eGFR decline rate in patients with CKD carrying high-risk ( N =239) and genetically matched low-risk ( N =1187) APOL1 genotypes. Exome sequencing revealed monogenic kidney diseases. Exome-wide association studies and gene-based and gene set-based collapsing analyses evaluated genetic modifiers of the effect of APOL1 genotype on CKD. Compared with genetic ancestry-matched patients with CKD with low-risk APOL1 genotypes, those with high-risk APOL1 genotypes had a higher risk of kidney failure (Hazard Ratio [HR]=1.58), a higher decline in eGFR (6.55 versus 3.63 ml/min/1.73 m 2 /yr), and were younger at time of kidney failure (45.1 versus 53.6 years), with the G1/G1 genotype demonstrating the highest risk. The rate for monogenic kidney disorders was lower among patients with CKD with high-risk APOL1 genotypes (2.5%) compared with those with low-risk genotypes (6.7%). Gene set analysis identified an enrichment of rare missense variants in the inflammasome pathway in individuals with high-risk APOL1 genotypes and CKD (odds ratio=1.90). In this genetically matched cohort, high-risk APOL1 genotypes were associated with an increased risk of kidney failure and eGFR decline rate, with a graded risk between specific high-risk genotypes and a lower rate of monogenic kidney disease. Rare missense variants in the inflammasome pathway may act as genetic modifiers of APOL1 effect on kidney disease.

Homeopathy as a saviour for urolithiasis: A narrative review shading light on pathophysiology of renal stones and homeopathy drugs

Kidney stone disease is a crystal concretion formed generally within the kidneys. It is an accumulative urological disorder of human health, affecting about 12% of the world population. Higher risk of kidney failure which has been associated with end stage renal failure. Calcium oxalate, which forms at Randall's plaque on the renal papillary surfaces, is the most common type of kidney stone. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone incident. The formation of the stone is a complex process which results from numerous physiochemical events such as, super saturation, nucleation, growth, aggregation, and retention of urinary stone constituents within tubular cells. Several therapies are being performed for kidney stone treatment, including thiazide diuretics, allopurinol, painkillers, dietary changes, shock-wave treatment, ureterenooscopic and percutaneous nephrolithotomy, and ureterenooscopic and percutaneous nephrolithotomy in severe cases. However, the side effects that these treatments possess and reoccurrence of the disease have motivated researchers to search for better and safer options. Homeopathic drugs as well as several medicinal plants display antiurolithiatic activity and thus perform an important role in treatment of kidney stone disease. Therefore, the present review thereby wants to bring to the attention the wonderful results that homeopathy is offering in cases of urolithiasis in a very non-invasive and economical way which is not yet popularized.

Progression of Kidney Disease in Kidney Transplant Recipients With a Failing Graft: A Matched Cohort Study.

Few studies have assessed outcomes in transplant recipients with failing grafts as most studies have focused on outcomes after graft loss. To determine whether renal function declines faster in kidney transplant recipients with a failing graft than in people with chronic kidney disease of their native kidneys. Retrospective cohort study. Alberta, Canada (2002-2019). We identified kidney transplant recipients with a failing graft (2 estimated glomerular filtration rate [eGFR] measurements 15-30 mL/min/1.73 m2 ≥90 days apart). We compared the change in eGFR over time (eGFR with 95% confidence limits, LCLeGFRUCL) and the competing risks of kidney failure and death (cause-specific hazard ratios [HRs], LCLHRUCL). Recipients (n = 575) were compared with propensity-score-matched, nontransplant controls (n = 575) with a similar degree of kidney dysfunction. The median potential follow-up time was 7.8 years (interquartile range, 3.6-12.1). The hazards for kidney failure (HR1.101.331.60) and death (HR1.211.592.07) were significantly higher for recipients, while the eGFR decline over time was similar (recipients vs controls: -2.60-2.27-1.94 vs -2.52-2.21-1.90 mL/min/1.73 m2 per year). The rate of eGFR decline was associated with kidney failure but not death. This was a retrospective, observational study, and there is a risk of bias due to residual confounding. Although eGFR declines at a similar rate in transplant recipients as in nontransplant controls, recipients have a higher risk of kidney failure and death. Studies are needed to identify preventive measures to improve outcomes in transplant recipients with a failing graft.