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Background COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. Methods We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. Results Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. Conclusions Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.

ObjectiveCommunity-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. The aim of this study is to investigate the links among kidney function, kidney function decline, and dementia incidence.MethodsWe analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed health care during 2006 to 2011, were ≥65 years of age, had no history of dementia, or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first year of observation and investigated its association with subsequent dementia risk.ResultsWe detected 18,983 cases of dementia (5.8% of participants) over a median follow-up of 5 years. Dementia incidence rates were progressively higher with lower eGFR: from 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR 2 mL/min/1.73 m2/y) within 1 year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer dementia. As many as 10% (95% CI 6%–14%) of dementia cases could be attributed to eGFR 2, a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.ConclusionsBoth lower kidney function and steeper kidney function decline are associated with the development of dementia.

BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes.METHODS: To assess whether eGFR declines RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect.CONCLUSIONS: Declines in eGFR CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.

BACKGROUND: The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%–10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. METHODS: Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. RESULTS: Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m(2) for class 2Ae, and from −1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m(2) for class 1. CONCLUSIONS: Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.

OBJECTIVES: To investigate pre- and post-operative renal global function and renal parenchymal volume (RPV) in both partial nephrectomy (PN) and radical nephrectomy (RN) utilizing film-based technology. PATIENTS AND METHODS: The patient cohort consisted of 81 and 82 cases with T1 tumors (≤ 7 cm) treated by PN and RN, respectively. Renal global function was assessed using the estimated glomerular filtration rate (eGFR), and RPV was measured using a Synapse Vincent volumetric analyzer which creates a reconstructed image from a computed tomography scan. Renal global function and RPV were evaluated pre-operatively and 6 months post-operatively. RESULTS: The percent eGFR decline of PN cases was significantly reduced compared with RN cases (p < 0.0001). Post-operative RPV of the contralateral side was significantly increased compared with pre-operative RPV (p < 0.0001) in RN cases. The percent change of the contralat-eral side RPV was slightly increased in RN compared with PN cases (p = 0.1881). A strong positive correlation was noted between post-operative eGFR and post-operative total RPV (r = 0.69, p < 0.0001), and a strong negative correlation was noted between percent eGFR decline and post-operative total RPV (r = −0.63, p < 0.0001). CONCLUSIONS: Prominent compensatory renal hypertrophy occurred within 6 months after RN. Post-operative renal functional outcome was closely correlated with the post-operative total RPV. In addition to RPV, further studies to unravel post-operative renal function from multifactorial aspects including surgical factors and intrinsic medical disease should be performed in the future.

Fibroblast growth factor 21 (FGF21) plays a role in kidney disease. Circulating FGF21 levels are associated with kidney function and progression in patients with type 2 diabetes (T2D). However, the association between FGF21 and kidney function in the general population is still lacking. The aim of this study was to determine the association between FGF21 and kidney function and its progression in a Chinese cohort. A total of 2425 participants from a population-based survey of diabetes and metabolic syndrome in Pinggu, Beijing, were included in the baseline analysis. After a median follow-up of 12 months, 2402 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 were analyzed in the longitudinal study. The progression of kidney function was defined as an eGFR decline exceeding 3.3% per year. Serum FGF21 levels were measured using an enzyme-linked immunosorbent assay at baseline. Male sex, body mass index (BMI), homeostasis model assessment of insulin resistance, higher levels of low-density lipoprotein cholesterol (LDL-c), uric acid, and FGF21 were associated with increased odds of a lower eGFR at baseline. The association of FGF21 with lower eGFR was independent of all the potential confounders in multivariable logistic regression (odds ratio, 1.005; 95% confidence interval 1.002–1.008). However, FGF21 was not associated with eGFR decline in the longitudinal analysis (odds ratio, 1.000; 95% confidence interval 0.998–1.001). Increased serum FGF21 levels were independently associated with lower eGFR in this nonmedicated general population. FGF21 could be a biomarker of kidney function in the general population.

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n =19; 14%) or low-risk (one or zero risk alleles; n =117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m 2 ; P =0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m 2 ; P =0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m 2 per year, P =0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline ( P =0.39) or any statistical interaction by APOL1 status ( P =0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

Approximately 7% to 9% of patients with donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) fail within 1 year post-DSA onset. However, little is known as to how this DSA-associated failure temporally progresses. This longitudinal study investigates DSA's temporal relationship to allograft dysfunction and identifies predictors of allograft function's progressive deterioration post-DSA.A cohort of 175 non-HLA identical patients receiving their first transplant between March 1999 and March 2006 were analyzed. Protocol testing for DSA via single antigen beads was done before transplantation and at 1, 3, 6, 9, and 12 months after transplantation then annually. Estimated glomerular filtration rate (eGFR) was analyzed before and after DSA onset.Forty-two patients developed DSA and had adequate eGFR information for analysis. Before DSA onset, the 42 patients had stable eGFR. By 1 year post-DSA, the cohort's eGFR was significantly lower (P0.001); however, 30 of 42 had stable function. Twelve patients had failure or early allograft dysfunction (eGFR decline25% from DSA onset). Those who failed early (by 1 year post-DSA) had more antibody-mediated rejection than stable patients (P=0.03). Late failures (after 1 year post-DSA) were predictable with evidence of early allograft dysfunction (eGFR decline25% by 1 year post-DSA; P0.001). Early allograft dysfunction preceded late failure by nearly 1 year.DSA is temporally related to allograft function deterioration. However, in many cases, late allograft failures are preceded by early allograft dysfunction. Therefore, monitoring for early allograft dysfunction provides treating physicians with a window of opportunity for treatment or continued monitoring.

RESULTS: 153 patients [23.5% (36 with >25% decline)/ 76.5% (117 with 25% decline); median follow up 48 months] were analyzed. More female (63.9% vs. 28.2%, p1⁄40.0001) and diabetic (41.7% vs. 26.2%, p1⁄40.021) patients had decrease of eGFR>25%. Median tumor size was significantly higher in the >25% eGFR decrease (2.8 vs. 2.4 cm, p1⁄40.005) as was median RENAL score (7 vs. 5, p 25% eGFR decline group. MVA demonstrated decreasing PPP (OR 1.4, p 25%. CONCLUSIONS: Absence of global renal ischemic insult does not protect the kidney from renal functional decline and a significant proportion of patients may yet go on to suffer significant decreases in GFR. Increasing tumor complexity and decreasing percentage parenchyma spared and female sex were independently associated with significant renal functional decline. Development of predictive computer modeling to aid in optimal patient selection and procedure planning may aid in optimizing renal functional outcomes.

Summary Background and objectives Sugar-sweetened soda is reported to be associated with increased risk for diabetes and albuminuria, but there are currently limited data on how sugar or artificially sweetened soda may be related to kidney function decline. Design, setting, participants, & measurements This study identified 3318 women participating in the Nurses’ Health Study with data on soda intake and albuminuria; of these, 3256 also had data on estimated GFR (eGFR) change between 1989 and 2000. Cumulative average beverage intake was derived from the 1984, 1986, 1990, 1994, and 1998 food frequency questionnaires. Serving categories included 1/mo (referent), 1 to 4/mo, 2 to 6/wk, 1 to 1.9/d, and 2/d. Microalbuminuria (MA) was considered a urinary albumin-tocreatinine ratio of 25 to 355 g/mg. For kidney function change, the primary outcome was a 30% decline in eGFR over 11 years; rapid eGFR decline defined as 3 ml/min per 1.73 m 2 per year was also examined. Results Consumption of 2 servings per day of artificially sweetened (diet) soda was independently associated with eGFR decline 30% (OR 2.02, 95% CI 1.36 to 3.01) and 3 ml/min per 1.73 m 2 per year (OR 2.20, 95% CI 1.36 to 3.55). No increased risk for eGFR decline was observed for 2 servings per day of diet soda. No associations were noted between diet soda and MA or sugar soda and MA or eGFR decline. Conclusions Consumption of 2 servings per day of artificially sweetened soda is associated with a 2-fold increased odds for kidney function decline in women. Clin J Am Soc Nephrol 6: 160–166, 2011. doi: 10.2215/CJN.03260410