Notes

Fast and Clean: LCME Clinical Strategy Education With out a Instructing Research laboratory.
The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio 17.89; 95% confidence interval 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model.

The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.
Caregivers are essential for the health, safety, and independence of many patients and incur financial and personal cost in this role, including increased burden and lower quality of life (QOL) compared to the general population. Extended-hours hemodialysis may be the preference of some patients, but little is known about its effects on caregivers.

Forty caregivers of participants of the ACTIVE Dialysis trial, who were randomized to 12 months extended (median 24 hours/wk) or standard (12 hours/wk) hemodialysis, were included. Utility-based QOL was measured by EuroQOL-5 Dimension-3 Level (EQ-5D-3L) and Short Form-6 Dimensions (SF-6D) and health-related QOL (HRQOL) was measured by the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS) and the Personal Wellbeing Index (PWI) at enrolment and then every 3 months until the end of the study.

At baseline, utility-based QOL and HRQOL were similar in both groups. At follow-up, caregivers of people randomizossibility that mode of dialysis delivery negatively impacts on caregivers supports the prioritization of research on burden and impact of service delivery in this population.
Acute kidney injury (AKI) affects 30% of adults hospitalized with hematologic malignancy. Little is known about the long-term impact on kidney outcomes in this population despite the close relationship between kidney function and malignancy treatment eligibility. The purpose of this population-based cohort study was to determine the effect of AKI on kidney function in the year following a new diagnosis of acute leukemia or lymphoma.

Participants were adults hospitalized within 3 weeks of malignancy diagnosis. Baseline kidney function was determined and AKI diagnosed using standardized criteria. PF04691502 Cox proportional hazard modeling examined the relationship between AKI and a≥30% decline in estimated glomerular filtration rate (eGFR) from baseline in the 1 year following hospitalization as the primary endpoint.

AKI occurred in 33% of 1064 participants, with 70% of episodes occurring within 48 hours of hospitalization, and significantly increased risk for a≥ 30% decline in eGFR (hazard ratio [HR] 2.7, 95% confidence interval [CI] 2.2-3.5) and incident chronic kidney disease (HR 2.2, 95% CI 1.7-2.8). AKI remained a significant predictor of eGFR decline in subgroup and multivariable analyses (adjusted HR 1.9, 95% CI 1.4-2.7). A≥ 30% decline in eGFR increased the risk for death within 1 year in participants with AKI (HR 2.1, 95% CI 1.3-3.3).

Results aid in identifying individuals at highest risk for poor outcomes and highlight the need for research involving interventions that preserve kidney function from the time of initial hospitalization with a hematologic malignancy into the postdischarge period.
Results aid in identifying individuals at highest risk for poor outcomes and highlight the need for research involving interventions that preserve kidney function from the time of initial hospitalization with a hematologic malignancy into the postdischarge period.
The impact of posttransplant red blood cell transfusion (RBCT) and their potential immunomodulatory effects on kidney transplant recipients are unclear. We examined the risks for adverse graft outcomes associated with post-kidney transplant RBCT.

We conducted a retrospective cohort study of all adult kidney transplant recipients at The Ottawa Hospital from 2002 to 2018. The exposure of interest was receipt of an RBCT after transplant categorized as 1, 2, 3 to 5, and >5 RBC. Outcomes of interest were rejection and death-censored graft loss (DCGL). Cox proportional hazards models were used to calculate hazard ratios (HR) with RBCT as a time-varying, cumulative exposure.

Among 1258 kidney transplant recipients, 468 (37.2%) received 2373 total RBCTs, 197 (15.7%) had rejection and 114 (9.1%) DCGL. For the receipt of 1, 2, 3 to 5, and >5 RBCT, compared with individuals never transfused, the adjusted HRs (95% confidence interval [CI]) for rejection were 2.47 (1.62-3.77), 1.27 (0.77-2.11), 1.74 (1.00-3.05), and 2.23 (1.13-4.40), respectively; DCGL 2.32 (1.02-5.27), 3.03 (1.62-5.64), 7.50 (4.19-13.43), and 14.63 (8.32-25.72), respectively. Considering a time-lag for an RBCT to be considered an exposure before an outcome to limit reverse causation, RBCT was not associated with rejection; the HRs for DCGL attenuated but remained similar. RBCT was also associated with a negative control outcome, demonstrating possible unmeasured confounding.

RBCT after kidney transplant is not associated with rejection, but may carry an increased risk for DCGL.
RBCT after kidney transplant is not associated with rejection, but may carry an increased risk for DCGL.
In pivotal trials of patients with autosomal dominant polycystic kidney disease at risk of rapid progression, tolvaptan slowed estimated glomerular filtration rate (eGFR) decline in early-to-moderate (TEMPO 34 [NCT00428948]) and moderate- to late-stage (REPRISE [NCT02160145]) chronic kidney disease (CKD). Discontinuation was less frequent in REPRISE (15.0%) than TEMPO 34 (23.0%), given that in REPRISE, only subjects who tolerated tolvaptan 60/30 mg daily initiated the double-blind phase. We evaluated whether the greater treatment effect in REPRISE was attributable to different completion rates.

We conducted
analyses of TEMPO 34 and REPRISE completers, defined as subjects who took trial drug to the end of the treatment period in TEMPO 34 (3 years) or REPRISE (1 year). Efficacy (rate of change in eGFR for tolvaptan vs. placebo) was analyzed as in each trial. Subjects from TEMPO 34 and REPRISE were also matched by propensity score for age, gender, and baseline eGFR to explore potential additional determinants of treatment effect.

The annualized tolvaptan treatment effect in TEMPO 34 completers (difference vs. placebo of 0.98 ml/min per 1.73 m
/y) and REPRISE completers (difference of 1.23) was similar to that of the respective total trial populations (TEMPO 34 0.94; REPRISE 1.27). The treatment effect of tolvaptan was also similar between matched subjects.

Greater treatment completion rate did not drive greater treatment effect in REPRISE. The more advanced CKD of REPRISE subjects may be more relevant. More rapid decline in kidney function in later-stage CKD enabled the effects of tolvaptan to be more easily discerned.
Greater treatment completion rate did not drive greater treatment effect in REPRISE. The more advanced CKD of REPRISE subjects may be more relevant. More rapid decline in kidney function in later-stage CKD enabled the effects of tolvaptan to be more easily discerned.
Immune checkpoint inhibitors (ICIs) are effective in treating several cancers; however, acute kidney injury (AKI) can occur as part as an immune-related adverse event (iRAE). Biomarkers at the time of AKI diagnosis may help determine whether they are ICI- related and guide therapeutic strategies.

In this retrospective study, we reviewed patients with cancer treated with ICI therapy between 2014 and 2020 who developed AKI (defined as a≥1.5-fold increase in serum creatinine [SCr]) that was attributed to ICI (ICI-AKI) and compared them with an adjudicated non-ICI-AKI group. Clinical and laboratory features, including SCr, serum C-reactive protein (CRP), and urine retinol binding protein/urine creatinine (uRBP/Cr) levels at AKI event were evaluated.

There were 37 patients with ICI-AKI and 13 non-ICI-AKI referents in the cohort for analysis. At time of AKI, SCr, CRP, and uRBP/Cr were significantly higher in the ICI-AKI compared with the non-ICI-AKI patients (median [interquartile range (IQR)] SCr 2.0 [1.7, 2.9] vs. 1.5 [1.3, 1.6] mg/dl, serum CRP 54.0 [33.7, 90.0] vs. 3.5 [3.0, 7.9] mg/l, and uRBP/Cr 1927 [1174, 46,522] vs. 233 [127, 989] μg/g Cr, respectively,
< 0.05 for all). Compared with the referent group, time from ICI initiation to AKI was shorter in the ICI-AKI patients. Among the ICI-AKI group, complete renal recovery occurred in 39% of patients by 3 months; rechallenge occurred in 16 (43%) of patients, of whom 3 (19%) had recurrence of AKI.

Our findings suggest that serum CRP and uRBP/Cr may help to differentiate AKI due to ICI from other causes.
Our findings suggest that serum CRP and uRBP/Cr may help to differentiate AKI due to ICI from other causes.
Connective tissue diseases, including systemic sclerosis and idiopathic inflammatory myopathies (IIMs), are a very rare cause of thrombotic microangiopathies (TMAs). Whether dysregulation of the complement pathways underlies these secondary forms of TMA and may be targeted by complement blocking agents remains elusive.

Kidney pathology and outcomes of 18 critically ill patients with TMA related to inflammatory myopathy flare-up (IIM,
=7) or scleroderma renal crisis (SRC,
=11; biopsy
=9) are assessed.

IIM-TMA is characterized by acute thrombotic lesions only, whereas SRC-TMA patients also harbored chronic vascular lesions and more interstitial fibrosis. C5b9 deposits, a marker of complement component 5 (C5) cleavage, were observed in the 2 subgroups at the junction of media and intima of arterioles, colocalizing with subendothelial edema. Thus, kidney biopsy distinguished between acute and chronic renal phenotypes that may help to individualize treatment. Treatment of IIM-TMA patients with combined full-code organ support, corticosteroids, B-cell depletion, and complement C5 blocking led to 1-year survival of 72%, compared with 19% in historical cohorts. Treatment of SRC-TMA was more heterogenous and relied on conversion enzyme inhibitor only or with eculizumab (
=6) and immunosuppressor (
=5). One-year survival of SRC-TMA patients was 52%, a result similar to historical cohorts. Eculizumab was followed by a rapid dramatic improvement of TMA in all the treated patients.

C5 blocking may reverse hematologic abnormalities in IIM- and SRC-TMA, and adding an early and aggressive immunosuppressive regimen may improve the survival of IIM-TMA. Underlying chronic vascular and interstitial lesions mitigate renal response in SRC-TMA.
C5 blocking may reverse hematologic abnormalities in IIM- and SRC-TMA, and adding an early and aggressive immunosuppressive regimen may improve the survival of IIM-TMA. Underlying chronic vascular and interstitial lesions mitigate renal response in SRC-TMA.
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