Rapid Decline In Renal Function Research Articles

Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan

ObjectiveGlomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred...

Mitophagy in Acute Kidney Injury and Kidney Repair.

Acute kidney injury (AKI) is a major kidney disease characterized by rapid decline of renal function. Besides its acute consequence of high mortality, AKI has recently been recognized as an independent risk factor for chronic kidney disease (CKD). Maladaptive or incomplete repair of renal tubules after severe or episodic AKI leads to renal fibrosis and, eventually, CKD. Recent studies highlight a key role of mitochondrial pathology in AKI development and abnormal kidney repair after AKI. As such, timely elimination of damaged mitochondria in renal tubular cells represents an important quality control mechanism for cell homeostasis and survival during kidney injury and repair. Mitophagy is a selective form of autophagy that selectively removes redundant or damaged mitochondria. Here, we summarize our recent understanding on the molecular mechanisms of mitophagy, discuss the role of mitophagy in AKI development and kidney repair after AKI, and present future research directions and therapeutic potential.

The crosstalk between hypoxia-inducible factor-1α and microRNAs in acute kidney injury.

Acute kidney injury (AKI) is a common critical clinical disease that is characterized by a rapid decline in renal function and reduced urine output. Ischemia and hypoxia are dominant pathophysiological changes in AKI that are induced by many factors, and the role of the “master” regulator hypoxia-inducible factor-1α (HIF-1α) is well recognized in AKI-related studies. MicroRNAs have been found to act as critical regulators of AKI pathophysiological process. More studies now have reported mutual interactions between HIF-1α and microRNAs in AKI. Therefore, in this brief review, we look into the mutual regulatory mechanisms between HIF-1α and microRNAs and discuss their function in the process of AKI. Recent studies demonstrated that HIF-1α is involved in the regulation of multiple functional microRNAs in AKI, and in turn, the level of HIF-1α is regulated by specific microRNAs. However, the role of the interactions between HIF-1α and microRNAs in AKI are controversial, and whether interventions targeting relevant mechanisms could achieve clinical benefits is not clear. Much work remains to further explore the value of targeting the HIF-1α-microRNA pathway in AKI treatment. Impact statement At first, we have discussed the role of hypoxia-inducible factor-1α (HIF-1α) and microRNAs in the acute kidney injury (AKI) pathophysiology. Then we have summarized the interactions between HIF-1α and microRNAs reported by AKI-related studies and concluded their regulatory effects in AKI process. Finally, we have made a vision of HIF-1α/microRNAs pathway’s potential as the intervention target in AKI. The mini review provides a systematic understanding of the crosstalk between HIF-1α and microRNAs in AKI and their effects on AKI pathophysiology and treatment.

Serum Ferritin Independently Predicts the Incidence of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

AimThis study aimed to determine whether serum ferritin (SF) is an independent risk factor of the incidence of chronic kidney disease (CKD) and rapid renal function decline (RFD) in male Tibetan patients with type 2 diabetes mellitus (T2DM).MethodsWe performed a retrospective cohort study that included 191 male Tibetan patients with T2DM without CKD. Patients were divided into three groups according to the level of SF. The following outcomes were measured: cumulative incidence of chronic kidney disease [i.e. estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 and/or urinary albumin/creatine ratio (ACR) ≥30 mg/g] and RFD (i.e. decrease in eGFR of ≥25% from baseline or a decline rate of ≥3 mL/min per 1.73 m2 annually).ResultsIn total, over a median follow-up period of 23 months, 30 (15.7%) and 89 patients (46.6%) developed CKD and RFD. In multivariable Cox models, a 100 ng/mL increment in SF was associated with a 1.12-fold (95% CI: 1.02–1.24) higher adjusted risk for incidence of CKD. The adjusted-HR of CKD was 1.31 (95% CI: 0.38–4.53) and 2.92 (95% CI: 0.87–9.77) for those in tertile 2 and tertile 3, respectively, compared with the patients in tertile 1. However, SF was not significantly associated with RFD (adjusted-HR: 1.06, 95% CI: 0.99–1.14).ConclusionSerum ferritin independently predicts the incidence of CKD in male Tibetan patients with T2DM. High levels of serum ferritin may play a role in the pathogenesis leading to the development of CKD in T2DM.

MiR-124/IRE-1α affects renal ischemia/reperfusion injury by regulating endoplasmic reticulum stress in renal tubular epithelial cells.

Acute kidney injury (AKI) refers to a clinical syndrome that occurs as a result of a rapid decline in renal function caused by multiple factors. Renal ischemia/reperfusion (I/R) injury is one of the main causes of AKI and has a high incidence and mortality. However, the specific pathogenesis of renal I/R injury is still unclear. In recent years, a major breakthrough has been made in the study of endoplasmic reticulum stress (ERS)-mediated apoptosis in I/R injury. It has been reported that miRNAs play protective roles in ischemic/reperfused organs, but the molecular mechanisms have not been investigated deeply. In this study, the renal I/R mouse model was used to explore the roles of miR-124 in ERS and in renal I/R injury. The western blot results showed that the expression levels of ERS-related proteins IRE-1α, XBP-1, and glucose-regulated protein 78 (GRP78) were significantly increased in the I/R model group when compared with those in the control group. Meanwhile, qPCR results showed that miR-124 expression was decreased in the I/R injury model, and overexpression of miR-124 using miR-124 mimics effectively reduced the expression of ERS-related proteins and alleviated renal I/R injury. In addition, luciferase reporter assay was performed, and the results showed that IRE-1α and miR-124 may have direct interaction. In conclusion, our data indicated that miR-124 was a negative regulator of ERS via binding to IRE-1α, ultimately conferring its protective effect on the kidney, which demonstrates the regulatory mechanism of miR-124 in renal I/R injury and provides new ideas and methods for the prevention and treatment of renal I/R injury.

Modifiable factors related to 7-year renal outcomes in subjects with type 2 diabetes and chronic kidney disease stage 3.

Background and Aims:Subjects with diabetes are prone to a rapid decline in renal function and major adverse cardiovascular events when they reach chronic kidney disease (CKD) stage 3. This study aimed to identify modifiable risk factors associated with the progression of CKD in this population.Settings and Design:An observational cohort study.Methods and Materials:A total of 320 type 2 diabetic patients with CKD stage 3 registered in the shared-care-system in our hospital in 2010 were regularly followed up for 7 years. Demographic, laboratory, medication, and fundus examination data of these subjects were collected and analyzed.Statistical Analysis Used:Cox regression was used to identify factors associated with changes in CKD stage.Results:During the 7-year follow-up period, 204 cases (63.7%) remained at CKD stage 3 while 79 cases (24.7%) progressed to stage 4 or 5 and 37 cases (11.6%) improved to stage 1 or 2. The change in estimated glomerular filtration rate (eGFR) in the first 2 years and variations in glycated hemoglobin (HbA1c) over 7 years were independent factors of both progression (hazard ratio (HR) 1.098 and 1.710, respectively) and improvement (HR 0.919 and 0.231, respectively) of CKD stage. Variations in systolic blood pressure (SBP) was also found as an independent factor for progression of renal function (HR 1.052).Conclusions:Our results demonstrated that fluctuations in HbA1c and SBP, and changes in eGFR during the first 2 years of treatment were associated with the long-term renal outcomes in type 2 diabetic patients with CKD stage 3.

Response: Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function (Diabetes Metab J 2019;43:840–53)

Response: Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function (<i>Diabetes Metab J</i> 2019;43:840–53)

Evaluation of Aetiology and Outcome of Acute Kidney Injury in a Tertiary Care Hospital of India- A Prospective Observational Study

Introduction: The Acute Kidney Injury (AKI) is a rapid decline in renal filtration function. The aetiological spectrum, prevalence of AKI and outcome is highly variable. This variation exists due to the difference in the criteria used, study population and demographic features. Huge differences are noted when AKI is compared in developing and developed countries. Hence, it is important to analyse the spectrum of AKI to facilitate earlier diagnosis and treatment which shall help in improving the outcome. Aim: To study the prevalence, aetiology and outcome of AKI in the medical intensive care. Materials and Methods: This was a prospective observational study conducted in a medical intensive care for 18 months where 1490 patients were screened and 403 patients were included as AKI by KDIGO criteria. History, examination, appropriate investigations and treatment details including dialysis were noted. The serum creatinine levels were obtained every day, to know the time of onset of AKI, at the time of death or discharge, and after one month for patients who turned up for follow-up. Patients were categorised based on outcome as survivors and nonsurvivors. Survivors were divided into as fully recovered and partially recovered and those who left the Intensive Care Unit (ICU) against medical advice were termed as lost to follow-up. Results: A total of 403 patients (27.04% of 1490) of medical intensive care admissions were found to have AKI. Sepsis was the most common cause of AKI. At the end of the month, 78.4% of AKI patients fully recovered, 1.2% partially recovered and the mortality was 14.9%. Mortality was higher in AKI associated with chronic medical conditions like cardiac failure, chronic liver disease and stroke. Conclusion: If treated early, AKI is mostly reversible. Regional differences in AKI should be studied extensively and local guidelines should be formulated by experts for prevention and early treatment, to improve the disease outcome.

Crescentic poststreptococcal acute glomerulonephritis accompanied by small vessel vasculitis: case report of an elderly male

BackgroundPoststreptococcal acute glomerulonephritis (PSAGN) in the elderly tends to have a severe clinical course and often presents with crescentic necrotizing glomerulonephritis in the renal biopsy. However, vasculitis lesions are unusual.Case presentationWe present a 71-year-old man who was admitted to our hospital for a recurrent gout attack with a rapid decline of renal function. Low C3 levels and a high anti-streptolysin O titer were observed, while myeloperoxidase- and proteinase 3- antineutrophil cytoplasmic antibody (ANCA) were negative. In addition to cellular crescent and necrosis lesions, diffuse peritubular capillaritis and venulitis as well as small arteriole vasculitis in the glomerular hilus were also apparent. Although granular C3c deposits in the capillary wall and hump lesions were not found, immunofluorescent staining for nephritis-associated plasmin receptor (NAPlr) and in situ zymography for plasmin activity were both positive. We thus diagnosed PSAGN accompanied by small vessel vasculitis. Steroid therapy gradually improved the patient’s renal function, and hemodialysis was discontinued after 1 month.ConclusionsIn our case, streptococcus infection might have concurrently provoked vasculitis, and NAPlr staining was useful for confirming diagnosis.

Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus.

Background SGLT-2 (sodium-glucose cotransporter-2) inhibitors are a novel class of oral hypoglycemic agents for the management of type 2 diabetes mellitus (T2DM). Herein, we aimed to assess the long-term effectiveness and safety of SGLT-2 inhibitors in a Southern Italy population of subjects affected by T2DM. Patients and Methods 408 diabetic patients treated with one of the three SGLT-2 inhibitors currently available in Italy (dapagliflozin, empagliflozin, and canagliflozin), either alone or in combination with other antidiabetic drugs, were retrospectively assessed at baseline, during, and after 18 months of continuous therapy. Results Treatment with SGLT-2 inhibitors resulted in a median decrease in HbA1c of 0.9%, with a percentage of decrement of 12 in relation to the baseline value, followed by a significant reduction (P < 0.001) in fasting plasma glucose. Variations in HbA1c occurred independently of the baseline clinical or biochemical characteristics. In addition, treatment with SGLT-2 inhibitors reduced body weight (P < 0.008) and decreased diastolic blood pressure (P = 0.004). With regard to safety outcomes, 66 patients out of 91 stopped SGLT-2 inhibitors during follow-up because of chronic or recurring genital infections, while the rest experienced other adverse events, such as urinary tract infections, polyuria, nausea, hypotension, dizziness, acute coronary event, worsening of glycemic control status, and rapid deterioration of renal function. Conclusion In our patients' population, the glycometabolic effects of SGLT-2 inhibitors were durable and comparable to those observed in multicenter randomized controlled trials. This notwithstanding safety concerns must be raised regarding the frequent occurrence of genitourinary infections and the risk of a rapid decline of renal function in patients with evidence of volume depletion and/or receiving other medications which can adversely affect kidney function.

Eleutheroside B Protects against Acute Kidney Injury by Activating IGF Pathway.

Acute kidney injury (AKI) is a common, complex, and severe clinical syndrome characterized by rapid decline in renal function, combined with tissue damage. Currently, the prevention and treatment of AKI are focused on symptomatic treatment, rather than treating the underlying causes. Therefore, there is no specific treatment to prevent renal injury except for renal dialysis. In this study, we used cisplatin-induced AKI mouse and human kidney-2 (HK-2) cell models to evaluate the renal protective effect of eleutheroside B, an active compound in traditional Chinese medicines. MTT assay was used to detect the effect of eleutheroside B on proliferation of human HK-2 cells in presence and in absence of cisplatin. Western blot and immunostaining were used to detect the protein level of kidney injury molecule-1 (KIM-1), cleaved caspase-3, receptor-interacting protein kinase (RIPK)-1, and RIPK-3. Real-time PCR was used to detect the mRNA levels of chemokines (like monocyte chemotactic protein 1, MCP-1) and pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). Flow cytometry assay was used to detect apoptosis of HK-2 cells. In vivo results showed that eleutheroside B reduced the increase in serum creatinine and blood urea nitrogen (BUN) levels in the AKI model. Periodic acid-Schiff staining and Western blot analysis of KIM-1 showed that eleutheroside B alleviated tubular cell injury. Further, eleutheroside B reduced macrophage infiltration and production of inflammatory cytokines, inhibited the activation of nuclear factor (NF)-κB, and inhibited apoptosis and programmed necrosis. The mechanism may be that eleutheroside B can activate the insulin-like growth factor (IGF) pathway and its downstream pathway by downregulating the expression of IGFBP-7, thus promoting cell proliferation. Therefore, our results suggest that eleutheroside B is a potential drug for AKI treatment.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions

ObjectiveTo assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DesignA prospective observational cohort study. ParticipantsAll inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. Main outcomesWe prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. ResultsOf 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18–1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20–1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03–1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01–1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05–1·18;p < 0·001). ConclusionsIn patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Arterial Stiffness Modulates the Association of Resting Heart Rate With Rapid Renal Function Decline in Individuals With Type 2 Diabetes Mellitus.

Resting heart rate (RHR) has been associated with cardiovascular risk, but data on renal outcomes are still scarce. We aimed to study the association of RHR with rapid renal function decline (RRFD) and to explore whether the association of RHR with RRFD is modulated by arterial stiffness in individuals with type 2 diabetes mellitus. Approach and Results: One thousand one hundred forty-two Asian people with type 2 diabetes mellitus were followed for 3.9±0.9 years in a regional hospital and a primary care facility. RRFD was defined as eGFR decline of 5 mL/min per 1.73 m2 or greater per year. Arterial stiffness was assessed by carotid-femoral pulse wave velocity. One hundred sixty-eight participants (15%) were classified as having RRFD. Participants with elevated RHR were younger, had higher levels of HbA1c, albuminuria, C-reactive protein, and pulse wave velocity. Compared with the lowest quartile, participants in quartile 4 had a higher risk for RRFD after adjustment for known risk factors (adjusted odds ratio 1.91 [1.11-3.28]). RHR improved discrimination and net reclassification for prediction of RRFD above traditional risk factors. Remarkably, arterial stiffness modulated the association of RHR with RRFD (P for interaction =0.03). RHR was significantly associated with risk of RRFD only in those with increased arterial stiffness (pulse wave velocity above age-reference value 7.7 m/s). RHR independently predicts RRFD, and the association is modulated by arterial stiffness. An elevated heart rate may be one factor in the spectrum of cardiovascular risk factors associated with renal functional impairment, especially in those with type 2 diabetes mellitus and an increased arterial stiffness.

Association of functional and structural social support with chronic kidney disease among African Americans: the Jackson Heart Study

BackgroundThere is limited evidence on the relationship between social support and renal outcomes in African Americans. We sought to determine the association of social support with prevalent chronic kidney disease (CKD) and kidney function decline in an African American cohort. We also examined whether age modifies the association between social support and kidney function decline.MethodsWe identified Jackson Heart Study (JHS) participants with baseline (Exam in 2000–2004) functional and structural social support data via the Interpersonal Support Evaluation List (ISEL) and social network size questions, respectively. With ISEL as our primary exposure variable, we performed multivariable regression models to evaluate the association between social support and prevalent CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin-creatinine ratio (ACR) ≥30 mg/g], eGFR decline, and rapid renal function decline (RRFD) (> 30% decrease in eGFR over approximately 10 years). All models were adjusted for baseline sociodemographics, diabetes, hypertension, smoking status, and body mass index; models for eGFR decline and RRFD were additionally adjusted for eGFR and ACR. In models for eGFR decline, we assessed for interaction between age and social support. For secondary analyses, we replaced ISEL with its individual domains (appraisal, belonging, self-esteem, and tangible) and social network size in separate models as exposure variables.ResultsOf 5301 JHS participants, 4015 (76%) completed the ISEL at baseline. 843 (21%) had low functional social support (ISEL score < 32). Participants with low (vs. higher) functional social support were more likely to have lower income (47% vs. 28%), be current or former tobacco users (39% vs. 30%), have diabetes (25% vs. 21%) or CKD (14% vs. 12%). After multivariable adjustment, neither ISEL or social network size were independently associated with prevalent CKD, eGFR decline, or RRFD. Of the ISEL domains, only higher self-esteem was associated with lower odds of prevalent CKD [OR 0.94 (95% CI 0.89–0.99)]. The associations between social support measures and eGFR decline were not modified by age.ConclusionsIn this African-American cohort, social support was not associated with prevalent CKD or kidney function decline. Further inquiry of self-esteem’s role in CKD self-management and renal outcomes is warranted.

SAT-285 DIABETES AND HIGHER HbA1c LEVELS ARE INDEPENDENTLY ASSOCIATED WITH ADVERSE RENAL OUTCOMES OVERTIME IN INPATIENTS WITH MULTIPLE HOSPITAL ADMISSIONS

Patients with diabetes commonly have multiple hospital admissions which potentially increases the risk of developing diabetes related complications in the future. The association between glycaemic status prior to the first hospital presentation and developing adverse renal outcomes overtime in patients with multiple hospital re-admissions is unclear but likely important. We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013-16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; (b) rapid decline in renal function (eGFR decline >5mL/min/1·73m²/year) and (c) final eGFR<30ml/min/1·73m². We used logistic regression analysis to assess the relationship between baseline glycaemic state and these outcomes. Of 4,126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR=1·42;95% CI:1·18-1·70;p<0·0001); (b) rapid decline in renal function (OR=1·40;95%CI:1·20-1·63;p<0·0001), and (c) reaching eGFR<30ml/min/1·73m² (OR=1·25;95%CI:1·03-1·53;p=0·024). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR=1·07;95% CI:1·01-1·4;p=0·029) and (b) rapid decline in renal function (OR=1·11;95% CI:1·05-1·18;p<0·0001).View Large Image Figure ViewerDownload Hi-res image Download (PPT) In patients with ≥ two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

MON-047 Monoclonal antibodies: Saviour of the gut vs an agent of kidney injury!

We present an interesting and unique case where a monoclonal antibody given to treat Crohn's disease, has been linked with fibrillary glomerulonephritis. A 39 year old caucasian British woman was referred for her deteriorating renal function in August 2016. She had a rise in creatinine from 109µmol/L (reference range 45-84µmol/L) to 188µmol/L in six months. Patient had a past medical history of Crohn’s disease diagnosed six years previously. Her treatment included courses of Mesalazine, Azathioprine (on and off for two years), Mercaptopurine, and corticosteroids (on and off during flare ups of crohn's). She was started on Adalimumab in April 2016 and a rapid decline in renal function was noted over the following four months. This is a retrospective case study and was picked up by the author when he followed up the patient in the renal outpatient clinic. The case was found unique and interesting as there is not much literature about Adalimumab as a cause for kidney injury and fibrillary glomerulonephritis. Patient's clinical notes, local electronic clinical data and slides/reports from histopathology department were requested and used to write this case report. Systemic examination of the patient was unremarkable and blood pressure was normal (120/70 mmHg). Peripheral pulses were intact with no bruits. Urinalysis showed 3+ blood with no protein (urine Albumin: Creatinine ratio 1.4mg/mmol, reference range <3mg/mmol). C3, C4 and immunoglobulins were in the normal range. Autoimmune screen including anti-nuclear antibodies (ANA) and anti-neutrophilic cytoplasmic antibodies (ANCA) were negative. There was no paraprotein band on serum electrophoresis, and urine free light chains were negative. A renal ultrasound showed normal sized kidneys with no obstruction or scarring. In the absence of a clear cause for her declining renal function, a renal biopsy was performed. This revealed significant interstitial fibrosis (Figure 1A). On electron microscopy there was evidence of fibrillary casts (Figure 1B) with ischaemic collapse of glomeruli and some foot process fusion.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The biopsy findings were compatible with tubulointerstitial nephritis with fibrillary glomerulonephritis (GN). This was though to be secondary to Adalimumab as kidney function declined four months after starting it and got better after discontinuation of Adalimumab. This is evident from the improvement of her serum creatinine value as depicted in the graph below (Figure 2). Fibrillary GN occurs in 1% of renal biopsies and pathogenesis of fibrillary GN remains unknown; no clinical findings are specific.

High-protein diet with renal hyperfiltration is associated with rapid decline rate of renal function: a community-based prospective cohort study.

The effect of a high-protein diet with renal hyperfiltration (RHF) on decline of kidney function has rarely been explored. We investigated the association between a high-protein diet, RHF and declining kidney function. A total of 9226 subjects from the Korean Genome and Epidemiology Study, a community-based prospective study (2001-14), were enrolled and classified into quartiles according to daily amount of protein intake based on food frequency questionnaires. RHF was defined as estimated glomerular filtration rate (eGFR) with residuals of >95th percentile after adjustment for age, sex, history of hypertension or diabetes, height and weight. Rapid decline of renal function was defined as decline rate of eGFR >3 mL/min/1.73m2/year. The relative risk of RHF was 3.48-fold higher in the highest than in the lowest protein intake quartile after adjustment for confounding factors [95% confidence interval (CI) 1.39-8.71]. The mean eGFR decline rate was faster as quartiles of protein intake increased. Furthermore, the highest quartile was associated with 1.32-fold increased risk of rapid eGFR decline (95% CI 1.02-1.73). When subjects were divided into two groups with or without RHF, the highest quartile was associated with a rapid decline in renal function only in RHF subjects (odds ratio 3.35; 95% CI 1.07-10.51). The sensitivity analysis using the Korean National Health and Nutrition Examination Survey (2008-15) data with 40113 subjects showed that higher quartile was associated with increased risk for RHF. A high-protein diet increases the risk of RHF and a rapid renal function decline in the general population. These findings suggest that a high-protein diet has a deleterious effect on renal function in the general population.

FP359Skin Autofluorescence Is Associated With Rapid Renal Function Decline In Subjects At Increased Risk Of Coronary Artery Disease

FP359Skin Autofluorescence Is Associated With Rapid Renal Function Decline In Subjects At Increased Risk Of Coronary Artery Disease

Skin autofluorescence is associated with rapid renal function decline in subjects at increased risk of coronary artery disease

Skin autofluorescence (AF) has been validated as a tool for estimating tissue advanced glycation end products (AGEs) accumulation and predicting long-term cardiovascular outcomes. However, whether measurements of skin AF could predict renal function decline remains controversial. From April, 2014 to April, 2015, we enrolled 245 subjects with at least two conventional risk factors for coronary artery disease (CAD). All were measured for body height and weight, blood pressure, plasma creatinine level, and skin AF at the start of the study. Baseline demographics and laboratory tests data were obtained by chart reviews and patient interviews. Serial plasma creatinine levels were followed regularly every 6–12 months for 2 years. In a stepwise multivariate linear regression analysis, skin AF, was an independent factor for predicting the relative renal function decline rate after adjustment of multiple covariates (ß = -0.036±0.016; p = 0.03). Subgroups analysis revealed that skin AF was a significant factor for relative renal function decline rate in subgroups of age < 65 years (ß = -0.068±0.024; p = 0.02), male sex (ß = -0.053±0.016; p< 0.01), body mass index≧25 Kg/m2(ß = -0.042±0.021; p = 0.04), and estimated glomerular filtration rate ≥ 60 ml/min/1.73m2(ß = -0.043±0.020; p = 0.04). However, only an interaction between skin AF and age attained significance (p for interaction = 0.04). Skin AF is a useful predictor for renal function decline in patients at increased risk of CAD.

Protective effect of sodium-glucose cotransporter2 inhibitors in patients with rapid renal function decline, stage G3 or G4 chronic kidney disease and type2 diabetes.

Aims/IntroductionThe risk of end‐stage kidney disease increases in proportion to the decline in the estimated glomerular filtration rate (eGFR). Although protective effects of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on the eGFR decline were shown in several large‐scale clinical trials, there are no studies investigating patients with a high risk of end‐stage kidney disease. We investigated the efficacy and safety of SGLT2i in advanced renal dysfunction patients (stage G3 or G4 of chronic kidney disease) with a rapid decline in eGFR.Materials and MethodsThis retrospective, longitudinal study enrolled patients with type 2 diabetes who were treated with SGLT2i, and whose eGFR was <60 mL/min/1.73 m2 and had declined >20% over 2 years (%ΔeGFR−2y) before initiating SGLT2i. The primary end‐point was the change in eGFR 2 years after initiation (%ΔeGFR+2y) compared with %ΔeGFR−2y.ResultsA total of 17 patients among 553 patients treated with SGLT2i for ≥2 years were included in the study. The average age, glycated hemoglobin and eGFR at SGLT2i initiation were 68.5 years, 7.3% and 38.3 mL/min/1.73 m2, respectively. %ΔeGFR+2y in patients who were treated with SGLT2i was significantly increased compared with the patients not treated with SGLT2i (2.3 and −21.7%, respectively; P < 0.0001). A multiple regression analysis showed that only the proportion of the rate of eGFR decline was the independent factor associated with improvement of %ΔeGFR+2y. There was no increase in serious adverse events including acute kidney injury.ConclusionsSGLT2i was safe, and prevented further eGFR decline in patients with type 2 diabetes and advanced renal dysfunction.