Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes

Reboldi, Gianpaolo; Verdecchia, Paolo; Fiorucci, G; Beilin, Lawrence J.; Eguchi, Katsumi; Imai, Yutaka; Kario, Kazuomi; Ohkubo, Takayoshi; Pierdomenico, Sante D.; Schwartz, Joseph E.; Wing, Lindon; Saladini, Francesca; Palatini, Paolo

doi:10.1016/j.kint.2017.07.013

Cited by 74 publications

(104 citation statements)

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“…Park et al reported a higher risk of developing hypertension and CVD in subjects with hyperfiltration after adjusting for confounding factors . Similarly, another study showed that hyperfiltration was a predictor of CVEs, independent of BMI and albuminuria . After excluding patients with diabetes from the analysis, the relationship remained significant.…”

Section: Resultsmentioning

confidence: 92%

“…Most of these studies also assessed all‐cause mortality, as described above. Six of the studies revealed significant associations between RHF and CVEs, and three reported associations between RHF and CV mortality; only two reported no significant associations between these outcomes and RHF …”

Section: Resultsmentioning

confidence: 97%

“…The majority of these studies were performed in general cohorts, while three included patients with type 2 diabetes, five included patients with prior CVD, and one included patients without diabetes and prior CVD . The assessments used to study GFR were heterogeneous: one used eGFR/kidney length and kidney volume, one used measured GFR (mGFR) by iohexol clearance, one used GFR measured by creatinine clearance, while the others used eGFR calculated with either Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and/or Modification of Diet in Renal Disease (MDRD) Equations …”

Section: Resultsmentioning

confidence: 99%

“…The relationship between hyperfiltration and CVEs was assessed in eight studies; the odds ratios that were provided in the studies are given in Figure . Most of these studies also assessed all‐cause mortality, as described above.…”

Section: Resultsmentioning

confidence: 99%

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Renal hyperfiltration defined by high estimated glomerular filtration rate: A risk factor for cardiovascular disease and mortality

Kanbay

Ertuğlu

Afsar

et al. 2019

Diabetes Obesity Metabolism

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Renal hyperfiltration, defined as an increased glomerular filtration rate above normal values, is associated with early phases of kidney disease in the setting of various conditions such as obesity and diabetes. Although it is recognized that glomerular hyperfiltration, that is, increased filtration per nephron unit (usually studied at low glomerular filtration levels and often referred to as single nephron hyperfiltration), is a risk factor for the progression of chronic kidney disease, the implications of having renal hyperfiltration for cardiovascular disease and mortality risk are incompletely understood. Recent evidence from diverse populations, including healthy individuals and patients with diabetes or established cardiovascular disease, suggests that renal hyperfiltration is associated with a higher risk of cardiovascular disease and all‐cause mortality. In this review, we critically summarize the existing studies, discuss possible mechanisms, and describe the remaining gaps in our knowledge regarding the association of renal hyperfiltration with cardiovascular disease and mortality risk.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Renal hyperfiltration defined by high estimated glomerular filtration rate: A risk factor for cardiovascular disease and mortality

Kanbay

Ertuğlu

Afsar

et al. 2019

Diabetes Obesity Metabolism

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“…If the ideal GFR is maintained in patients with a solitary kidney, there may be less risk of glomerulosclerosis. In support of negative effects of hyperfiltration or hypertrophy, positive eGFR slopes or high eGFR values are associated with adverse outcomes in adults [18, 19]. …”

Section: Discussionmentioning

confidence: 99%

Trajectory of Estimated Glomerular Filtration Rate Predicts Renal Injury in Children with Multicystic Dysplastic Kidney

Matsumura¹,

Sugii²,

Awazu³

2018

Nephron

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Background/Aims: Children with a solitary functioning kidney have a risk of renal injury caused by hyperfiltration. Timely intervention with renin-angiotensin inhibitors may be beneficial. We examined whether trajectory of estimated glomerular filtration rate (eGFR) would predict renal injury, defined as microalbuminuria/proteinuria, hypertension, and/or a decline in eGFR. Methods: Seventeen patients (male 7, female 10) with multicystic dysplastic kidney (MCDK; median age 13 years, range 6–19 years) followed in our clinic were examined retrospectively. An eGFR decline was defined as a fall to < 90 mL/min/1.73 m² or a decline of > 5 mL/min/1.73 m²/year for those with baseline eGFR of ≥90 or < 90 mL/min/1.73 m² respectively. Results: Nine patients had renal injury at the time of investigation. Compared with 8 patients without renal injury, those with renal injury tended to be older (14.7 ± 4.2 vs. 11.4 ± 4.6 years) and the birth weight was smaller (2,538 ± 281 vs. 2,966 ± 361 g, p < 0.05). The frequency of contralateral congenital anomaly of kidney and urinary tract (cyst, hydronephrosis, or vesicoureteral reflux) were not different. The trajectory of eGFR in those without renal injury was either an increase (n = 3) or unidentifiable (n = 5), whereas that in the renal injury group was exclusively an increase followed by decline (p < 0.05). The average age of the onset of eGFR decline was 9.4 ± 4.2 years and that of the start of renal injury (albuminuria/proteinuria 5, eGFR decline 4, hypertension 1) was 12.5 ± 4.2 years. Conclusion: All the children with MCDK who developed renal injury had eGFR trajectory of increase followed by decline. Renal injury followed the peak eGFR by 3 years on average. This observation is in agreement with the hyperfiltration theory and underscores the importance of following eGFR trajectory closely.

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Association of Glomerular Hyperfiltration and Cardiovascular Risk in Middle-Aged Healthy Individuals

et al. 2020

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IMPORTANCE Glomerular hyperfiltration is associated with increased risk of cardiovascular disease in high-risk conditions, but its significance in low-risk individuals is uncertain. OBJECTIVE To determine whether glomerular hyperfiltration is associated with increased cardiovascular risk in healthy individuals. DESIGN, SETTING, AND PARTICIPANTS This was a prospective population-based cohort study, for which enrollment took place from August 2009 to October 2010, with follow-up available through March 31, 2016. Analysis of the data took place in October 2019. The cohort was composed of 9515 healthy individuals, defined as individuals without hypertension, diabetes, cardiovascular disease, estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m 2 , or statin and/or aspirin use, identified among 20 004 patients aged 40 to 69 years with health information accessed through the CARTaGENE research platform. EXPOSURES Individuals with glomerular hyperfiltration (eGFR >95th percentile after stratification for sex and age) were compared with individuals with normal filtration rate (eGFR 25th-75th percentiles). MAIN OUTCOMES AND MEASURES Adverse cardiovascular events were defined as a composite of cardiovascular mortality, myocardial infarction, unstable angina, heart failure, stroke, and transient ischemic attack. Risk of adverse cardiovascular events was assessed using Cox and fractional polynomial regressions and propensity score matching. RESULTS From the 20 004 CARTaGENE participants, 9515 healthy participants (4050 [42.6%] male; median [interquartile range] age, 50.4 [45.9-55.6] years) were identified. Among these, 473 had glomerular hyperfiltration (median [interquartile range] eGFR, 112 [107-115] mL/min/1.73 m 2) and 4761 had a normal filtration rate (median [interquartile range] eGFR, 92 [87-97] mL/min/1.73 m 2). Compared with the normal filtration rate, glomerular hyperfiltration was associated with an increased cardiovascular risk (hazard ratio, 1.88; 95% CI, 1.30-2.74; P = .001). Findings were similar with propensity score matching. The fractional polynomial regression showed that only the highest eGFR percentiles were associated with increased cardiovascular risk. The cardiovascular risk of individuals with glomerular hyperfiltration was similar to that of the 597 participants with an eGFR between 45 and 60 mL/min/1.73 m 2 (hazard ratio, 0.90; 95% CI, 0.56-1.42; P = .64). CONCLUSIONS AND RELEVANCE These findings suggest that glomerular hyperfiltration is independently associated with increased cardiovascular risk in middle-aged healthy individuals. This risk profile appears to be similar to stage 3a chronic kidney disease.

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Glomerular hyperfiltration is a predictor of adverse cardiovascular outcomes

Cited by 74 publications

References 50 publications

Renal hyperfiltration defined by high estimated glomerular filtration rate: A risk factor for cardiovascular disease and mortality

Renal hyperfiltration defined by high estimated glomerular filtration rate: A risk factor for cardiovascular disease and mortality

Trajectory of Estimated Glomerular Filtration Rate Predicts Renal Injury in Children with Multicystic Dysplastic Kidney

Association of Glomerular Hyperfiltration and Cardiovascular Risk in Middle-Aged Healthy Individuals

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