P0279DIABETIC KIDNEY DISEASE VERSUS CHRONIC KIDNEY DISEASE IN ADULTS WITHOUT DIABETES MELLITUS: A RENAL SURVIVAL ANALYSIS

Abstract Background and Aims Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease, but the decline in kidney function varies considerably between chronic kidney diseases (CKD), and determinants of renal function loss, early in the course of the disease, are still a matter of debate. Method We retrospectively examined the renal outcome at 31 July 2017 of 309 CKD patients (age 59.1 (50.1-68.6) years; 60% male; eGFR 32.7 (21.7-44.8) mL/min) admitted in our hospital during January 2007-December 2012 with a median follow up time of 7.2 (95%CI, 6.8-7.6) years. Only patients who had at least 3 admissions and who were alive during the study period were included. CKD was defined as the presence of an eGFR <60ml/min/1.73m2 or the presence of albuminuria >30mg/g creatinine for more than 3 months. The primary endpoint was renal survival defined as renal replacement therapy (RRT) initiation. Factors affecting renal survival were evaluated in a Cox proportional hazard model. Results DKD (24%), glomerular (GN, 24%), tubulo-interstitial (TIN, 27%) and vascular nephropathies (VN, 25%) were the causes of CKD. Patients with DKD (66.8 (56.5-72.2) years) and VN (68.5 (59.7-76.2) years) were older than those with GN (50.3 (37.4-59.0) years) and TIN (55.6 (45.8-61.8) years). Moreover, the highest cardiovascular comorbidity score was found in patients with VN and DKD (p<0.001). Median eGFR decline was -1.23 ( -3.39 – 0.35) mL/min/year; 29% of the patients had CKD progression of >3mL/min/year and 14% had rapid progression (>5mL/min/year). Patients with GN had the lowest eGFR (26.8 (19.1-38.9) versus DKD 36.2 (23.4-47.7), VN 34.9 (22.4-51.0), TIN 32.4 (21.8-44.8) mL/min, p<0.001), the fastest eGFR decline (-3.1 versus DKD -1.9, VN -1, TIN -1,2 mL/min/year, p 0.5) and the highest proteinuria (2.7 versus DKD 1.4, VN 0.4, TIN 0.6 g/24h, p<0.001). During follow up, 29% of the studied patients started RRT; mean renal survival time for the entire cohort was 7.4 (95%CI, 7.0-7.8) years. CKD cause (versus DKD p=0.04, Figure 1), lower eGFR (HR 0.89 (95%CI, 0.85-0.93)), elevated albuminuria (HR 1.4 (95%CI, 1.2-1.7)), higher total serum cholesterol (HR 1.00 (95%CI, 1.00-1.01)) and elevated mean arterial blood pressure (HR 1.03 (95%CI, 1.00-1.06)) were associated with RRT initiation in the Cox regression model. Conclusion Patients with DKD and VN had similar poorer renal survival as compared with GN and TIN. Earlier referral to the diabetic renal clinic and intensive management of the modifiable risk factors (albuminuria, hypercholesterolemia, hypertention) are necessary to retard progression of CKD and, subsequently, prolong renal survival.

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A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

Scientific Reports ◽

10.1038/s41598-021-84715-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Li Tan ◽

Yi Tang ◽

Gaiqin Pei ◽

Zhengxia Zhong ◽

Jiaxing Tan ◽

...

Keyword(s):

Risk Factors ◽

Iga Nephropathy ◽

Cox Regression ◽

Renal Outcome ◽

Matched Cohort ◽

Negative Group ◽

Renal Survival ◽

Cox Regression Analysis ◽

Renal Outcomes

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

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Relationship between renal biopsy and renal survival in elderly patients with chronic kidney disease: A propensity score matching approach

10.21203/rs.3.rs-21517/v1 ◽

2020 ◽

Author(s):

Xiaowei Lou ◽

Shizhu Yuan ◽

Wei Shen ◽

Yueming Liu ◽

Juan Jin ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Elderly Patients ◽

Renal Biopsy ◽

Cox Regression ◽

Renal Survival ◽

Aged Patients ◽

Renal Outcomes ◽

Propensity Matching

Abstract Background The effect of renal biopsy on the prognosis of elderly patients with chronic kidney disease remains unclear. Thus, in this study, we aimed to evaluate the relationship between renal biopsy and renal survival in this population.Methods In this multi-centre retrospective study, the baseline characteristics among three groups were balanced by propensity matching. All patients were divided into three groups according to age and renal biopsy. The clinicopathological features at biopsy and renal outcomes during the follow-up were collected and analysed. Renal outcomes were defined as estimated glomerular filtration rate < 15 mL/min/1.73 m2, dialysis, renal transplantation, or death. The prognostic effects of renal biopsy were evaluated using Cox regression models. Results A total of 1313 patients were identified. After propensity matching, 390 patients were selected and divided into three groups. After a total follow-up period of 55 months, 20 (13.3%) patients (47.6% group 1 vs 7.41% group 2 vs 39.1% group 3) reached renal outcomes. No significant differences were found in renal outcomes among aged patients whether they underwent renal biopsy or not. Cox regression analysis revealed risk factors in aged patients including low albumin and high levels of proteinuria and serum creatinine (P < 0.05). Platelet count was significant only in aged patients who underwent renal biopsy (hazard ratio: 0.642, P < 0.05). Conclusion In conclusion, renal biopsy in the elderly has not shown benefits in terms of renal survival, conservative treatment appears to be a viable therapeutic option in the management of those people.

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FRI0181 ORGAN DAMAGE FREE SURVIVAL IN SOUTHERN CHINESE PATIENTS WITH ACTIVE LUPUS NEPHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2552 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 674.1-674

Author(s):

C. C. Mok ◽

C. S. Sin ◽

K. C. Hau ◽

T. H. Kwan

Keyword(s):

Lupus Nephritis ◽

Regression Model ◽

Cox Regression ◽

Organ Damage ◽

Renal Survival ◽

Cox Regression Model ◽

Free Survival ◽

Renal Response

Background:The goals of treatment of lupus nephritis (LN) are to induce remission, retard the progression of chronic kidney disease, prevent organ complications and ultimately reduce mortality. Previous cohort studies of LN have mainly focused on the risk of mortality and development of end stage renal failure (ESRF) (renal survival). The cumulative frequency of LN patients who survive without organ damage, which correlates better with the balance between treatment efficacy and toxicity, as well as quality of life, has not been well studied.Objectives:To study the organ damage free survival and its predictive factors in patients with active LN.Methods:Consecutive patients who fulfilled ≥4 ACR/SLICC criteria for SLE and with biopsy proven active LN between 2003 and 2018 were retrospectivey analyzed. Those with organ damage before LN onset were excluded. Data on renal parameters and treatment regimens were collected. Complete renal response (CR) was defined as normalization of serum creatinine (SCr), urine P/Cr (uPCR) <0.5 and inactive urinary sediments. Partial renal response (PR) was defined as ≥50% reduction in uPCR and <25% increase in SCr. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). The cumulative risk of having any organ damage or mortality since LN was studied by Kaplan-Meier’s analysis. Factors associated with a poor outcome were studied by a forward stepwise Cox regression model, with entry of covariates with p<0.05 and removal with p>0.10.Results:273 LN patients were identified but 64 were excluded (organ damage before LN onset). 211 LN patients were studied (92% women; age at SLE 30.4±13.5 years; SLE duration at LN 1.9±3.1years). 47 (22%) patients had nephrotic syndrome and 60 (29%) were hypertensive. Histological LN classes was: III/IV±V (75.1%), I/II (7.8%) and pure V (17.1%) (histologic activity and chronicity score 7.0±4.2 and 1.8±1.5, respectively). Induction regimens were: prednisolone (33.1±17.5mg/day) in combination with intravenous cyclophosphamide (CYC) (21.4%; 1.0±0.2g per pulse), oral CYC (8.6%; 96.4±37.8mg/day), azathioprine (AZA) (14.3%; 78.6±25.2mg/day), mycophenolate mofetil (MMF) (22.8%; 1.9±0.43g/day) and tacrolimus (TAC) (17.1%; 4.3±1.1mg/day). After a follow-up of 8.6±5.4 years, 94(45%) patient developed organ damage (SDI≥1) and 21(10%) patients died. The commonest organ damage was renal (36.3%) and musculoskeletal (17.9%), and the causes of death were: infection (38.1%), malignancy (19.0%), cardiovascular events (9.5%) and ESRF complications (9.5%). At last visit, 114 (55%) patients survived without any organ damage. The cumulative organ damage free survival at 5, 10 and 15 years after renal biopsy was 73.5%, 59.6% and 48.3%, respectively. The 5, 10 and 15-year renal survival rate were 95.2%, 92.0% and 84.1% respectively. In a Cox regression model, nephritic relapse (HR 3.72[1.78-7.77]), proteinuric relapse (HR 2.30[1.07-4.95]) and older age (HR 1.89[1.05-3.37]) were associated with either organ damage or mortality, whereas CR (HR 0.25[0.12-0.50]) at month 12 were associated with organ damage free survival. Baseline SCr, uPCR and histological LN classes were not significantly associated with a poor outcome. Among patients with class III/IV LN, the long-term organ damage free survival were not significantly different in users of MMF (reference) from CYC (IV/oral) (HR 1.45[0.76- 2.75]) or TAC (HR 1.03[0.26-1.62]) as induction therapy.Conclusion:Organ damage free survival is achieved in 55% of patients with active LN upon 9 years of follow-up. CYC/MMF/TAC based induction regimens did not differ for the long-term outcome of LN. Targeting complete renal response and preventing renal relapses remain important goals of LN treatment.Acknowledgments:NILDisclosure of Interests:None declared

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Association of Dyskalemias with Ischemic Stroke in Advanced Chronic Kidney Disease Patients Transitioning to Dialysis

American Journal of Nephrology ◽

10.1159/000516902 ◽

2021 ◽

pp. 1-9

Author(s):

Ankur A. Dashputre ◽

Keiichi Sumida ◽

Fridtjof Thomas ◽

Justin Gatwood ◽

Oguz Akbilgic ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Ischemic Stroke ◽

Kidney Disease ◽

Lower Risk ◽

Chronic Exposure ◽

Cox Regression ◽

Acute Exposure ◽

Continuous Exposure ◽

Advanced Chronic Kidney Disease

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates <30 mL/min/1.73 m2 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K <3.5 mEq/L] and hyperkalemia [K >5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q1–Q3) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. Discussion/Conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.

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Recovery of new-onset kidney disease in COVID-19 patients discharged from hospital

BMC Infectious Diseases ◽

10.1186/s12879-021-06105-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nan-Hui Zhang ◽

Yi-Chun Cheng ◽

Ran Luo ◽

Chun-Xiu Zhang ◽

Shu-Wang Ge ◽

...

Keyword(s):

Kidney Disease ◽

Kidney Diseases ◽

Descriptive Statistics ◽

Limited Information ◽

High Discharge ◽

Discharged Patients ◽

Recovery Group ◽

Abundant Data ◽

New Onset

Abstract Background Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge. Methods Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used. Results In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51–70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven’t recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group. Conclusions Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine.

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The Relationship Between Blood Pressure Variability And Renal Progression In Hypertensive Patients With Chronic Kidney Disease

Gevher Nesibe Journal, IESDR ◽

10.46648/gnj.270 ◽

2021 ◽

Vol 6 (14) ◽

pp. 80-88

Author(s):

Huseyin Duru ◽

Ekrem KARA

Keyword(s):

Blood Pressure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Blood Pressure Measurement ◽

Rapid Progression ◽

Night Time ◽

Hypertensive Patients ◽

Significant Difference ◽

Renal Progression

Objective: To evaluate the effect of 24 hour systolic blood pressure (SBP) and diastolic blood pressure (DBP) variability (BPV) on renal progression in hypertensive patients with chronic kidney disease (CKD) Methods: A total 59 hypertensive patients (mean age: 54.2±14.6 years, 50.8% male) with CKD who underwent 24 hours ambulatory blood pressure measurement (ABPM) were included. Data on SBP, DBP, BPV coefficients (VC) for SBP (SBP-CV) and DBP (DBP-CV) were recorded. A decrease in e-GFR of <5 ml/min/year was considered as normal renal progression and a decrease in ≥5 ml/min/year was considered as rapid renal progression. Results: Overall, 40.6% of the patients had uncontrolled HT, while 45.8% had non-dipper pattern. Mean±SD daytime and night-time SBP and SBP-VC values were 135.3±17.9 mmHg, 128.6±23.0 mmHg, 11.7±2.8 and 9.5±3.6, respectively. Mean±SD daytime and nigh-time DBP and DBP-VC values were 84.5±13.4 mmHg, 77.2±16.1 mmHg, 13.8±3.8 and 12.0±3.7, respectively. Rapid renal progression was detected in 25.4% of patients with no significant difference in daytime, night-time and total SBP, SBP-VC, DBP and DBP-VC values between patients with rapid vs. natural renal progression. The regression analysis adjusted for age, gender, presence of DM, baseline e-GFR and dipping status revealed no significant impact of SBP-VC and DBP-VC in predicting rapid progression (p> 0.05). Conclusion: In conclusion, our finding revealed no significant association between BPV and renal progression in hypertensive patients with CKD. Larger scale prospective, randomized controlled trials with longer follow-up are needed to clarify this issue.

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Recovery of kidney function in patients treated with maintenance dialysis—a report from the ERA-EDTA registry

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa368 ◽

2020 ◽

Author(s):

Lily Jakulj ◽

Anneke Kramer ◽

Anders Åsberg ◽

Johan de Meester ◽

Carmen Santiuste de Pablos ◽

...

Keyword(s):

Kidney Disease ◽

Kidney Function ◽

Cox Regression ◽

Kidney Diseases ◽

Early Event ◽

Tubular Necrosis ◽

Kidney Replacement Therapy ◽

Maintenance Dialysis ◽

One Year ◽

End Stage

Abstract Background Literature on recovery of kidney function (RKF) in patients with end-stage kidney disease treated with maintenance dialysis (i.e. over 90 days) is limited. We assessed the incidence of RKF and its associated characteristics in a European cohort of dialysis patients. Methods We included adult patients from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry who started maintenance dialysis in 1997-2016. Sustained RKF was defined as permanent discontinuation of dialysis. Temporary discontinuation of ≥ 30 days (non-sustained RKF) was also evaluated. Factors associated with RKF adjusted for potential confounders were studied using Cox-regression analyses. Results RKF occurred in 7,657 (1.8%) of 440,996 patients of whom 71% experienced sustained RKF. Approximately 90% of all recoveries occurred within the first two years after day 91 of dialysis. Of patients with non-sustained RKF, 39% restarted kidney replacement therapy within one year. Sustained RKF was strongly associated with the following underlying kidney diseases (as registered by the treating physician): tubular necrosis (irreversible) or cortical necrosis (adjusted Hazard Ratio [aHR]: 20.4, 95%CI: 17.9-23.1), systemic sclerosis (aHR: 18.5, 95%CI: 13.8-24.7) and hemolytic uremic syndrome (aHR: 17.3, 95%CI: 13.9-21.6). Weaker associations were found for hemodialysis as first dialysis-modality (aHR: 1.5, 95%CI: 1.4-1.6) and dialysis initiation at an older age (aHR: 1.8, 95%CI: 1.6-2.0) or in a more recent time-period (aHR: 2.4, 95%CI: 2.1-2.7). Conclusions Definitive discontinuation of maintenance dialysis is a rare and not necessarily an early event. Certain clinical characteristics, but mostly the type of underlying kidney disease, are associated with a higher likelihood of RKF.

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Pre-eclampsia and risk of later kidney disease: nationwide cohort study

BMJ ◽

10.1136/bmj.l1516 ◽

2019 ◽

pp. l1516 ◽

Cited By ~ 22

Author(s):

Jonas H Kristensen ◽

Saima Basit ◽

Jan Wohlfahrt ◽

Mette Brimnes Damholt ◽

Heather A Boyd

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Outcome Measure ◽

Cox Regression ◽

Hazard Ratio ◽

Hazard Ratios ◽

Gestational Age At Delivery ◽

History Of

ABSTRACTObjectiveTo investigate associations between pre-eclampsia and later risk of kidney disease.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.Main outcome measureHazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.ResultsThe cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.Conclusions Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.

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Hemoglobinuria Is a Risk Factor For Kidney Disease Progression In Sickle Cell Anemia

Blood ◽

10.1182/blood.v122.21.996.996 ◽

2013 ◽

Vol 122 (21) ◽

pp. 996-996

Author(s):

Santosh L. Saraf ◽

Xu Zhang ◽

Tamir Kanias ◽

James P. Lash ◽

Robert E. Molokie ◽

...

Keyword(s):

Steady State ◽

Kidney Disease ◽

Kidney Function ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Red Blood Cell Transfusion ◽

Free Hemoglobin ◽

Arterial Blood

Abstract Chronic kidney disease (CKD) is a frequent complication of sickle cell anemia (SCA) and is a predictor of early mortality. To determine the predictors of deteriorating kidney function in SCA, we followed 164 patients treated at the University of Illinois at Chicago for a median of 32 months (range 3-88 months). Steady-state estimated glomerular filtration (eGFR), albuminuria, and hemoglobinuria assessments were obtained at baseline and during the follow-up period. Steady-state was defined as greater than four weeks from a vaso-occlusive pain episode or a red blood cell transfusion. Hemoglobinuria was defined as positive for blood on dipstick and < 2 red blood cells on microscopy. Fifty-six (34%) of the patients had hemoglobinuria at baseline. We confirmed in a subset of 43 patients that dipstick positive hemoglobinuria (n=17) was associated with higher urine cell-free hemoglobin concentrations determined by ELISA than dipstick negative urine (n=26) (23.1 vs. 11.5 ng/mL, p<0.0001) (Figure 1). Age and mean arterial blood pressures were similar in patients with hemoglobinuria at baseline compared to those without but markers of hemolysis were higher (LDH, indirect bilirubin, AST, and reticulocyte percentage; p<0.0001). Sixty-one percent (95%CI: 48-73%) of patients with hemoglobinuria at baseline had hemoglobinuria at most recent follow up compared to 9% (95%CI: 5-18%) of patients without hemoglobinuria at baseline (p<0.0001). The proportion of patients with CKD progression defined by a 50% reduction in eGFR calculated by the CKD-EPI formula or requirement for hemodialysis or kidney transplant was higher in patients with baseline hemoglobinuria (13%, 7/56) versus without hemoglobinuria (1%, 1/108) (HR 14, 95%CI: 2-113; logrank p=0.001) (Figure 2). Progression of albuminuria category from normoalbuminuria (albuminuria < 30mg/g creatinine) to either microalbuminuria (albuminuria = 30-300 mg/g creatinine) or macroalbuminuria (albuminuria > 300mg/g creatinine) or microalbuminuria to macroalbuminuria was also higher in patients with baseline hemoglobinuria (42%, 11/26) versus without hemoglobinuria (13%, 9/67) (HR 3.1, 95%CI: 1.3-7.7; logrank p=0.004) (Figure 3). In conclusion, hemoglobinuria determined by urinalysis at steady-state is a valid assessment of increased urine cell-free hemoglobin concentration and is fairly consistent on repeat testing at steady-state visits. The presence of hemoglobinuria is significantly associated with a greater risk for progression of CKD and albuminuria. Our findings are consistent with the possibility that cell-free hemoglobin contributes to the progression of kidney disease in SCA. Further research including measures to decrease cell-free hemoglobin exposure to preserve kidney function are warranted.Figure 1Figure 1. Figure 2Figure 2. Figure 3Figure 3. Disclosures: No relevant conflicts of interest to declare.

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Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3465 ◽

2015 ◽

Vol 100 (4) ◽

pp. 1368-1375 ◽

Cited By ~ 48

Author(s):

C. H. Lee ◽

E. Y. L. Hui ◽

Y. C. Woo ◽

C. Y. Yeung ◽

W. S. Chow ◽

...

Keyword(s):

Regression Analysis ◽

Diabetic Nephropathy ◽

Cox Regression ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Baseline Serum ◽

Cox Regression Analysis ◽

Egfr Decline

Background: Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. Method: Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. Results: At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m2, serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01–1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥60 mL/min/1.73 m2 and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06–1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1–3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. Conclusions: Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.

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