Rate Of Kidney Function Decline Research Articles

The Gut Microbial Metabolite Trimethylamine N -oxide, Incident CKD, and Kidney Function Decline.

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes kidney injury and tubulointerstitial fibrosis. Little is known about prospective associations between TMAO and kidney outcomes, especially incident CKD. We hypothesized that higher plasma TMAO levels would be associated with higher risk of incident CKD and greater rate of kidney function decline. We included 10,564 participants from two community-based, prospective cohorts with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 to assess incident CKD. TMAO was measured using targeted mass spectrometry at baseline and one follow-up visit. Creatinine and Cystatin C were measured up to 4 times during follow-up and used to compute eGFR. Incident CKD was defined as an eGFR decline ≥ 30% from baseline and a resulting eGFR<60 ml/min/1.73 m2. Time-varying Cox models assessed the association of serial TMAO measures with incident CKD, adjusting for sociodemographic, lifestyle, diet, and cardiovascular disease risk factors. Linear mixed models assessed the association with annualized eGFR change in 10,009 participants with at least one follow-up eGFR measure without exclusions for baseline eGFR levels. During a median follow-up of 9.4 years (interquartile range: 9.1-11.6 years), 979 incident CKD events occurred. Higher TMAO levels associated with higher risk of incident CKD (2nd to 5th vs. 1st quintile HR[95%CI]= 1.65 [1.22-2.23], 1.68 [1.26-2.25], 2.28 [1.72-3.02], and 2.24[1.68-2.98], respectively) and greater annualized eGFR decline ( 2nd to 5th vs. 1st quintile annualized eGFR change= -0.21 [-0.32, -0.09], -0.17 [-0.29, -0.05], -0.35 [-0.47, -0.22], and -0.43[-0.56, -0.30], respectively) with monotonic dose-response relationships. These associations were consistent across different racial/ethnic groups examined. The association with eGFR decline was similar to or larger than that seen for established CKD risk factors including diabetes, per 10 mmHg of higher systolic blood pressure, per 10 years of older age, and Black race. In community-based US adults, higher serial measures of plasma TMAO were associated with higher risk of incident CKD and greater annualized kidney function decline.

Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria.

To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting. We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m2, who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization. We assessed the effects of SGLT2 inhibitors on renal function (changes in eGFR slope/time). Index date was defined as the date of the first dispensing of SGLT2 inhibitors. Annual baseline slope was calculated using all eGFR measurements during the 2 years prior to index date (median = 7 measurements), while annual follow-up slope was calculated from all evaluations during 90-900 days post index date, along with baseline measurement at index date (median = 6 measurements). Paired t tests were used to compare differences between baseline and follow-up annual slopes. Of a total of 354 participants with CKD, without diabetes, who received SGLT2 inhibitors and were followed for a median of 527 days, the mean age was 72.8 ± 11.8 years, 26% were female, and 91% used renin-angiotensin system blockade. The mean eGFR was 45.4 ± 9.5 mL/min/1.73 m2. The mean body mass index was 29.1 ± 5.4 kg/m2. During the year before index date, 146 participants (41%) had a urinary albumin to creatinine ratio (UACR) <30 mg/g, 81 (23%) had a UACR of 30-300 mg/g, 74 (21%) had a UACR >300 mg/g, and 53 (15%) had no UACR evaluation. The mean eGFR slope over time was -5.6 ± 7.7 mL/min/1.73 m2 per year at baseline, which improved to -1.7 ± 6.8 mL/min/1.73 m2 per year after SGLT2 inhibitor administration (p <0.001). This effect was independent of UACR. In a real-world study of primarily older non-diabetic adults with CKD, SGLT2 inhibition was associated with a slower rate of kidney function decline, regardless of baseline UACR level.

HYDROchlorothiazide versus placebo to PROTECT polycystic kidney disease patients and improve their quality of life: study protocol and rationale for the HYDRO-PROTECT randomized controlled trial

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) leads to progressive renal cyst formation and loss of kidney function in most patients. Vasopressin 2 receptor antagonists (V2RA) like tolvaptan are currently the only available renoprotective agents for rapidly progressive ADPKD. However, aquaretic side effects substantially limit their tolerability and therapeutic potential. In a preliminary clinical study, the addition of hydrochlorothiazide (HCT) to tolvaptan decreased 24-h urinary volume and appeared to increase renoprotective efficacy. The HYDRO-PROTECT study will investigate the long-term effect of co-treatment with HCT on tolvaptan efficacy (rate of kidney function decline) and tolerability (aquaresis and quality of life) in patients with ADPKD.MethodsThe HYDRO-PROTECT study is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized clinical trial. The study is powered to enroll 300 rapidly progressive patients with ADPKD aged ≥ 18 years, with an eGFR of > 25 mL/min/1.73 m2, and on stable treatment with the highest tolerated dose of tolvaptan in routine clinical care. Patients will be randomly assigned (1:1) to daily oral HCT 25 mg or matching placebo treatment for 156 weeks, in addition to standard care.OutcomesThe primary study outcome is the rate of kidney function decline (expressed as eGFR slope, in mL/min/1.73 m2 per year) in HCT versus placebo-treated patients, calculated by linear mixed model analysis using all available creatinine values from week 12 until the end of treatment. Secondary outcomes include changes in quality-of-life questionnaire scores (TIPS, ADPKD-UIS, EQ-5D-5L, SF-12) and changes in 24-h urine volume.ConclusionThe HYDRO-PROTECT study will demonstrate whether co-treatment with HCT can improve the renoprotective efficacy and tolerability of tolvaptan in patients with ADPKD.

Poor glycemic control is associated with more rapid kidney function decline after the onset of diabetic kidney disease.

The role of glycemic control and its variability on the rate of kidney function decline after the onset of diabetic kidney disease (DKD) remains unclear. The association between baseline HbA1c and rates of estimated GFR (eGFR) loss during follow-up was examined by mixed-effects linear regression in 530 individuals with type 1 diabetes and early-to-moderate DKD from the Preventing Early Renal Loss (PERL) trial, and 2,378 individuals with type 2 diabetes and established DKD from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. The benefit of intensive vs. standard glycemic control in slowing eGFR decline was examined in ACCORD. The associations between continuous glucose monitoring-derived short-term glycemic variability indices and rate of GFR decline were also evaluated in PERL. A higher baseline HbA1c was associated with a more negative eGFR slope in both PERL and ACCORD (-0.87 and -0.27 ml/min/1.73m2/year per Hba1c unit increment, p<0.0001 and p=0.0002, respectively). In both studies, the strength of this association progressively increased with increasing levels of albuminuria (p for interaction <0.05). Consistent with this, the benefit of intensive glycemic control on eGFR decline was greater in ACCORD participants with severe than in those with moderate albuminuria (+1.13 vs. +0.26 ml/min/1.73 m2/year, p=0.01). No independent associations were found in PERL between short-term glycemic variability indices and rate of eGFR decline. In both type 1 and type 2 diabetes, poor glycemic control is associated with a more rapid rate of GFR decline after DKD onset, especially in persons with severe albuminuria.

Higher beta-hydroxybutyrate ketone levels associated with a slower kidney function decline in ADPKD.

Dysregulated energy metabolism is a recently discovered key feature of autosomal dominant polycystic kidney disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate (BHB) concentrations are associated with reduced disease progression in patients with ADPKD. We analyzed data from 670 patients with ADPKD participating in the Developing Intervention Strategies to Halt Progression of ADPKD (DIPAK) cohort, a multi-center prospective observational cohort study. BHB was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting or had missing BHB levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. Of the participants, 61% were female, with an age of 47.3±11.8 years, a height-adjusted total kidney volume (htTKV) of 834 [interquartile range (IQR) 495-1327] mL/m and an estimated glomerular filtration rate (eGFR) of 63.3±28.9mL/min/1.73 m2. The median concentration of BHB was 94 (IQR 68-147) µmol/L. Cross-sectionally, BHB was associated neither with eGFR nor with htTKV. Longitudinally, BHB was positively associated with eGFR slope {B=0.35mL/min/1.73 m2 [95% confidence interval (CI) 0.09 to 0.61], P=.007}, but not with kidney growth. After adjustment for potential confounders, every doubling in BHB concentration was associated with an improvement in the annual rate of eGFR by 0.33mL/min/1.73 m2 (95% CI 0.09 to 0.57, P=.008). These observational analyses support the hypothesis that interventions that raise BHB concentration could reduce the rate of kidney function decline in patients with ADPKD.

Postpartum progression of chronic kidney disease in patients with chronic glomerulonephritis

Background: In the recent years, pregnancy outcomes in women with primary chronic glomerulonephritis (CGN) have been encouraging despite increased incidence of complications and preterm birth. However, the impact of pregnancy on CKD progression in glomerulonephritis remains understudied.&#x0D; Aim: To evaluate the effect of pregnancy on CKD progression in the postpartum period in patients with primary CGN.&#x0D; Materials and methods: This was an observational longitudinal study. The study group included 40 patients with CGN and CKD G1G3b, who had 40 deliveries from January 2009 to November 2022. The control group included 35 patients with CGN who had no pregnancies after CKD was diagnosed. Serum creatinine and estimated glomerular filtration rate (GFR) were assessed during the follow up, recording the development of CKD G5.&#x0D; Results: The annual rate of GFR decline in the study group was -4.6 [-8.0; -2.5] ml/min/1.73 m2, and in the control group -1.8 [-5.8; +1.5] ml/min/1.73 m2 (p = 0.056). After complicated pregnancy (preeclampsia, placental insufficiency, increase in proteinuria, worsening of arterial hypertension, acute kidney injury), the annual rate of GFR decline was -6.4 [-13.4; -3.5] ml/min/1.73 m2, which was higher than in the controls (p = 0.042). There were no significant differences in survival without GFR decrease by 30%, 50% and without CKD G5 between the study and the control groups. However, CKD G5-free survival in the patients with complicated pregnancy was lower than that in the controls (p = 0.022) and in those with uncomplicated pregnancies (p = 0.009).&#x0D; Eleven (11) of 40 patients in the main group and 3/35 in the control group reached CKD G5. The time from delivery to CKD G5 was 4.83 [2.08; 7.07] years. Among women who reached end-stage renal failure after childbirth, there were significantly more patients with CKD G3, proteinuria 1 g/day during pregnancy, arterial hypertension at baseline and during pregnancy, preeclampsia, acute kidney injury, delivery at less than 37 weeks of gestation, with neonates requiring treatment at intensive care unit, and unfavorable pregnancy outcomes.&#x0D; Conclusion: Renal survival in the women with primary CGN who had been pregnant was not significantly different from that in the women who did not have pregnancies; however, complicated pregnancy increased the rate of kidney function decline.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20ml/min/1.73 m2 after 1year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

Trajectories of kidney function and risk of mortality.

We aimed to identify patterns within the rate of kidney function decline, determinants of these patterns and their association with all-cause mortality risk in the general population. Participants aged ≥ 45 years with at least one assessment of creatinine-based estimated glomerular filtration rate (eGFR) taken between 1997 and 2018 were selected from a population-based cohort study. Analyses were performed using several distinct latent class trajectory modelling methods. Cumulative incidences were calculated with 45 years of age as the starting point. In 12062 participants (85922 eGFR assessments, mean age 67.0 years, 58.7% women, median follow-up 9.6 years), four trajectories of eGFR change with age were identified: slow eGFR decline [rate of change in mL/min/1.73m2 per year (RC), -0.9; 95% CI, -0.9 to -0.9; reference group], intermediate eGFR decline (RC, -2.5; 95% CI, -2.7 to -2.5) and fast eGFR decline (RC, -4.3; 95% CI, -4.4 to -4.1), and an increase/stable eGFR (RC, 0.3; 95% CI, 0.3 to 0.4). Women were more likely to have an increase/stable eGFR [odds ratio (OR), 1.94; 95% CI, 1.53 to 2.46] whereas men were more likely to have a fast eGFR decline (OR, 1.86; 95% CI, 1.33 to 2.60). Participants with diabetes, cardiovascular disease (CVD) or hypertension were more likely to have an intermediate or fast eGFR decline. All-cause mortality risks (cumulative incidence at age of 70 years) were 32.3% (95% CI, 21.4 to 47.9, slow eGFR decline), 6.7% (95% CI, 3.5 to 12.4, intermediate eGFR decline), 68.8% (95% CI, 44.4 to 87.8, fast eGFR decline) and 9.5% (95% CI, 5.5 to 15.7, increase/stable eGFR). Sex, hypertension, diabetes and CVD were identified as trajectory membership determinants. Having fast eGFR decline was associated with the highest risk of all-cause mortality, highlighting the need for extensive monitoring and prevention of kidney function decline in individuals at risk of having fast eGFR decline.

Rate of Kidney Function Decline is Associated With Kidney and Heart Failure in Individuals With Type 1 Diabetes

Diabetes is the most common cause of chronic kidney disease (CKD). Urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) are commonly used to monitor the onset and progression of diabetic kidney disease (DKD). We studied if the preceding rate of kidney function decline, that is, the eGFR slope, is independently associated with incident clinical cardiorenal events. This study included longitudinal data for 2498 Finnish individuals with type 1 diabetes (T1D). The eGFR slope was calculated from 5 years preceding the study visit. Data on kidney failure, coronary heart disease (CHD), stroke, 3-point major adverse cardiovascular events (MACE), heart failure, and death were obtained from national registries. The associations between the eGFR slope and incident events were assessed with multivariable competing risk models during the average follow-up of 9.2 years. The eGFR slopes were associated (P≤ 0.001) with all outcomes when adjusted for age, sex, and HbA1c. However, eGFR slope remained associated only with the composite outcome of kidney failure or death when the albuminuria group and eGFR at the study visit were included in the model (P= 0.041). In addition, eGFR slope was independently associated with kidney failure in individuals without CKD (eGFR > 60 ml/min per 1.73 m2; P= 0.044), and with heart failure in those with CKD (P= 0.033). However, eGFR slope did not markedly improve the model C-index. The eGFR slope was independently associated with kidney failure in those without CKD, and with heart failure in those with CKD. However, it is unlikely to have major relevance for clinical practice when the current eGFR and albuminuria status are known.

1226-P: A Rapid Rate of Kidney Function Decline Is Associated with Increased Risk of Heart Failure in Patients with Type 2 Diabetes—Results from ACCORD Study

Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D. We further assessed whether accounting for the rate of estimated glomerular filtration rate (eGFR) decline over time improved prediction of HF risk as compared to standard clinical predictors. Included in the study were 9,192 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with available baseline urinary albumin-to-creatinine ratio (UACR) data and ≥3 eGFR measurements during follow-up. The association between rapid kidney function decline (eGFR loss ≥5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during follow-up was estimated by logistic regression. We calculated integrated discrimination improvement (IDI) by adding rapid kidney function decline to HF predictors. Over a median follow-up of 5.0 years (interquartile range 4.1-5.7), 1,432 participants (15.6%) experienced rapid kidney function decline and 355 (3.9%) experienced a HF event. Rapid kidney function decline was associated with a 3.57-fold increase in HF odds (odds ratio [OR] 3.57; 95% confidence interval [CI] 2.86-4.45). This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline and censoring (OR 4.47; 95% CI 3.7-6.11). Adding rapid kidney function decline during follow-up to other predictors (WATCH-DM score, eGFR, and UACR) significantly improved HF risk classification (relative IDI=+49%, p&amp;lt;0.0001). In patients with T2D, rapid kidney function decline was associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF prediction in patients with T2D. Disclosure A.Bano: None. C.Bueno junior: None. Y.Tang: None. X.Sun: None. E.Hall: None. J.Mitri: Other Relationship; Novo Nordisk, Research Support; Kowa Company, Ltd. M.Morieri: Advisory Panel; Merck Sharp &amp; Dohme Corp., Amarin Corporation, Servier Laboratories, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. H.Shah: None. A.Doria: None. Funding National Heart, Lung, and Blood Institute (N01HC95178, N01HC95179, N01HC95180, N01HC95181, N01HC95182, N01HC95183, N01HC95184, IAAY1HC-9035, IAAY1HC1010); National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; Centers for Disease Control and Prevention; General Clinical Research Centers

12-LB: Clinical Impact of Risk Profiling with KidneyIntelX on DKD Progression in a Large Integrated Health Care System

KidneyIntelXTM combines 3 plasma biomarkers with clinical variables to categorize adults with DKD stages 1-3b for risk of a progressive decline in kidney function over 5 years. We previously demonstrated that using KidneyIntelX to assess risk and guide treatment does lead to optimized medication use, lifestyle changes, and specialist referrals. We now report the one-year pre and posttest clinical impact on eGFR slope and hemoglobin A1C (HbA1c) in the Mount Sinai Health System. Among the 1087 patients with follow-up data, the median age was 69 years, 52% were women, 32% self-identified Black, baseline eGFR 59 ml/min/1.73m2, baseline HbA1c was 7.2%, and 146 (13%), 439 (40%), and 502 (46%) were scored as high, intermediate, and low risk by KidneyIntelX. In high-risk patients, median eGFR slope slowed from -5.7 ml/min/year pre-test to -2.1 ml/min/year post-test (p&amp;lt;0.001), and from -1.8 ml/min/year to -1.0 ml/min/year in intermediate-risk (p=0.005) (Table). The median HbA1c decreased from 8.4 to 7.7% (p&amp;lt;0.001) in high risk, and from 7.5 to 7.2% (p&amp;lt;0.001) in intermediate risk. In conclusion, deployment and risk stratification by KidneyIntelX was associated with reduced rate of kidney function decline and improved glycemic control, particularly in those scored as high risk. Disclosure J. Tokita: Other Relationship; Renalytix. C. Sinfield: None. M. J. Donovan: Employee; Renalytix. T. McNicholas: Employee; Renalytix. M. Kattan: Research Support; Novo Nordisk. Consultant; Renalytix, Verici. Research Support; Bayer Inc. D. W. Lam: None.

#3682 THE KETONE BODY BETA-HYDROXYBUTYRATE IS ASSOCIATED WITH BETTER KIDNEY FUNCTION OUTCOME IN PATIENTS WITH ADPKD: RESULTS OF THE DIPAK COHORT

Abstract Background and Aims A dysregulated energy metabolism is a key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD), characterized by cystic cells being dependent on glucose and poorly able to use other energy sources such as ketone bodies. Besides providing energy, ketone bodies, especially beta-hydroxybutyrate, can act as signaling metabolites and reduce inflammation and oxidative stress. In experimental studies, raising ketone body concentration reduced disease progression. Therefore, we hypothesized that higher endogenous serum beta-hydroxybutyrate concentration reduces disease progression in patients with ADPKD. Method We analyzed data from the DIPAK cohort, a prospective observational cohort study that included 670 patients with ADPKD. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. We excluded participants with type 2 diabetes, who used disease-modifying drugs (e.g., tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. Results The median concentration of beta-hydroxybutyrate was 94 (IQR 68–147) μmol/L. Of the participants, 61% were female, the mean age was 47.3 ± 11.8 years, and the mean estimated glomerular filtration rate (eGFR) was 63.3 ± 28.9 mL/min/1.73 m2. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with kidney volume. Longitudinally, beta-hydroxybutyrate was positively associated with the eGFR slope (B = 0.37 (95% CI 0.11 to 0.62), p = 0.005) but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration reduced the annual rate of eGFR loss by 0.34 (95% CI 0.10 to 0.58, p = 0.005) ml/min/1.73 m2. Conclusion These analyses support the hypothesis that raising the beta-hydroxybutyrate concentration, one of the ketone bodies, reduces the rate of kidney function decline in patients with ADPKD.

Describing Natural History and Exploring Risk Factors for Kidney Function Decline in Persons With CKD of Uncertain Etiology in Sri Lanka

Chronic kidney disease of uncertain etiology (CKDu) is a leading cause of death of adults in Sri Lanka's dry region. We initiated the Kidney Progression Project (KiPP) to prospectively follow 292 persons with Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (eGFR) 20 to 60 ml/min per 1.73 m2 living in a CKDu endemic area. Using data from 3-year follow-up, we assessed kidney function decline (>30% from baseline eGFR), and the composite outcome of >30% eGFR decline, eGFR<15 ml/min or death, and explored the association of the 2 outcomes with baseline demographic, residential, and clinical parameters accounting for baseline eGFR. Median eGFR at enrollment was 28 ml/min among 71 women; 30 ml/min among 221 men; 91% to 99% had trace or no proteinuria during follow-up. At enrollment, median serum sodium, uric acid, and potassium were 143 mmol/l, 6.3 mg/dl, 4.5 meq/l, respectively among women; and 143 mmol/l, 6.9 mg/dl, 4.3 meq/l among men. Mean slope of eGFR decline was-0.5 (SD 4.9) ml/min/yr. In exploratory analyses, men with greater years of education and those living in northern region of the study area experienced lower likelihood of disease progression (hazard ratios [HR] 0.87 [0.77-0.98] per additional year and 0.33 [0.12-0.89] for northern versus other subregions, respectively). There was a suggestion that men drinking well water had higher likelihood and men living further away from reservoirs had lower likelihood of >30% decline in eGFR (HR 2.07 [0.95-4.49] for drinking well water versus not, and HR 0.58 [0.32-1.05] per kilometer distance, respectively). The overall rate of kidney function decline was slow in this CKDu cohort, similar to other nonalbuminuric CKD, and event rates were similar among men and women. Further etiologic investigations could focus on specific residence locale and water use.

Risk factors associated with the discordance in kidney function decline rate in identical twins.

The rate of kidney function decline is different for each individual regardless of any difference in the medical histories. This study set out to identify the risk factors for high discordance in kidney function decline in an identical twin cohort. This study included 333 identical twins from the Korean Genome and Epidemiology Study who were categorized into two groups according to the estimated glomerular filtration rate (eGFR) decline: the slow and rapid progressor groups. The mean differences of variables were compared between the two groups. We calculated the difference in the annual eGFR change between twins and analyzed the risk factors associated with high discordance in twins who had > 5 mL/min/1.73 m2 /yr of the intra-twin difference in the annual eGFR decline. Identical twins with diabetes and baseline eGFR < 60 mL/min/1.73 m2 were excluded. The high discordance twins showed significant differences in body mass index; waist-to-hip ratio; total body fat percentage; and levels of blood hemoglobin, serum fasting glucose, albumin, triglyceride, and uric acid; however, there were no differences in low discordance twins. Multivariable logistic regression showed that blood hemoglobin level is the only significant factor associated with high discordance of eGFR decline in twins. Blood hemoglobin level may play a role in the individual differences in kidney function decline.

Risk factors for progression of chronic kidney disease: An investigation in prepubertal children.

Previous studies on progression of chronic kidney disease (CKD) in children have included older post-pubertal subjects. This study attempted to evaluate risk factors for progression of CKD in pre-pubertal children. An observational study of children aged 2-10 years with an eGFR within the limits of >30 and<75 mL/min/1.73 m2 was performed. Presenting clinical and biochemical risk factors, as well as diagnosis, were analysed for their association with progression to kidney failure, time to kidney failure and for the rate of decline of kidney function. One hundred and twenty-five children were studied of whom 42 (34%) had progressed to CKD stage 5 during the median period of follow up of 3.1 (IQR=1.8-6) years. Hypertension, anaemia and acidosis at entry were associated with progression but they did not predict reaching the end point. Only glomerular disease, proteinuria and stage 4 kidney disease were independent predictors of kidney failure and the time to kidney failure. The rate of kidney function decline was greater in patients with glomerular than non-glomerular disease. Common modifiable risk factors, when present at initial evaluation, were not independently associated with CKD progression to kidney failure in prepubertal children. Only non-modifiable risk factors and proteinuria predicted eventual stage 5 disease. The physiological changes of puberty may be the major precipitator of kidney failure during adolescence.

Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy Study

Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. Observational cohort. 118 consecutive patientswith biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls. Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting. Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months. Correlation and time to event analysis. Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level(r=0.562, P<0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P=0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P=0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline (r=0.238, P=0.01) but did not predict dialysis-free survival. Small sample size; lack of serial measurement. Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use.

Clinical and Pathological Features of Chinese Patients with Type 2 Diabetes, Biopsy-Proven Diabetic Kidney Disease, and Rapid eGFR Decline.

ObjectiveThe rate of kidney function decline in patients with diabetic kidney disease (DKD) is known to differ. This study analyzed the clinicopathologic features and related risk factors affecting long-term renal survival in Chinese type 2 diabetic patients with rapid estimated glomerular filtration rate (eGFR) decline.MethodsIn this retrospective descriptive study, 191 DKD patients were first classified as rapid eGFR decliners and slow eGFR decliners on the basis of the median eGFR slope value (−8.0 mL/min/1.73 m2/year). In total, 96 patients with rapid eGFR decline were included in the analyses and subsequently allocated to end-stage renal disease (ESRD) and non-ESRD groups. Baseline clinicopathological data of rapid eGFR decliners were collected. Cox proportional hazard analysis was performed to calculate the hazard ratios (HRs) for progression to ESRD.ResultsDuring a median follow-up of 25 months, 52 (54.2%) rapid eGFR decliners progressed to ESRD. These 52 rapid eGFR decliners had poorer renal function, lower hemoglobin and albumin concentrations, higher total cholesterol and baseline proteinuria levels, and more severe interstitial inflammation than those who did not progress to ESRD. After adjustment for age, gender, baseline eGFR, proteinuria, hemoglobin level, serum albumin concentration, and histopathologic parameters, multivariate Cox proportional hazard analysis revealed that eGFR (HR 0.973, 95% CI 0.956–0.989) and proteinuria (HR 1.125, 95% CI 1.030–1.228) were associated with the increased risk of progression to ESRD.ConclusionHigher proteinuria and lower eGFR were independent risk factors for renal progression in Chinese patients with type 2 diabetes and rapid eGFR decline.

The Role of Exercise Training in Delaying Kidney Function Decline in Non-Dialysis-Dependent Chronic Kidney Disease

Chronic Kidney Disease (CKD) is a progressive condition characterised by declining eGFR and associated, particularly in advanced stages, with increased morbidity and cardiovascular mortality. Current treatment options for delaying disease progression are limited to a small number of pharmacological agents. Considering that rates of kidney function decline are greater in patients with lower levels of habitual physical activity, there is interest in the potential benefits of structured exercise training in delaying CKD progression. This discursive review summarises the current state-of-play in this field of research by critically analysing the published systematic reviews of randomised controlled trials of structured exercise training in the non-dialysis CKD population. Several issues are highlighted that hamper definite conclusions as to the therapeutic effectiveness of exercise training for this purpose. However, following an overview of the pathophysiology and risk factors for kidney function decline, several potential mechanisms explaining how exercise training may benefit CKD progression are offered. Finally, suggestions for future research in this area are made. The review concludes that there is a need for further research on the effectiveness of exercise before it can be recommended as part of routine care for the purpose of delaying CKD progression. Exercise can be recommended, however, to individual patients because of a potential benefit to kidney function, and definite benefits to other outcomes such as quality of life, with no apparent evidence of harm.

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study

Introduction: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. Methods: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0–25%], moderate [26–50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. Results: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m²] of 1.34 [95% CI: −2.56 to 5.23], 3.50 [95% CI: −0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10–3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52–5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. Conclusion: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

Urinary Monocyte Chemoattractant Protein-1 in Patients With Alport Syndrome

In patients with Alport syndrome, the rate of kidney function decline varies with genotype, chromosomal sex, and possibly other factors.1 We hypothesized that certain urinary biomarkers can predict the rate of kidney function decline in patients with Alport syndrome. We collected urine samples from 76 patients with Alport syndrome (39 male, 37 female) recruited through the Alport Syndrome Treatments and Outcomes Registry (ClinicalTrials.gov identifiers NCT00481130 and NCT01602835) and from 40 healthy adult and 11 healthy pediatric volunteers.