Sandrine Lemoine

Validation of Renal Oxidative Metabolism Measurement by Positron-Emission Tomography

Either in research or in clinical practice, the exploration of renal oxidative metabolism is limited by the lack of noninvasive measurement. Positron-emission tomography using carbon-11 acetate may estimate tissue oxidative metabolism by measuring acetate turnover in the Krebs cycle. Although extensively studied in cardiology, this method has never been validated for renal oxidative metabolism measurement. The aim of this study is the validation of acetate turnover compared with the invasive renal oxygen consumption measurement. Renal oxygen consumption and tubular sodium reabsorption were measured invasively in 10 anesthetized pigs. Simultaneously, acetate turnover was estimated by the clearance of carbon-11 acetate in the renal cortex, after a 166-MBq injection of carbon-11 acetate. Renal oxidative metabolism was measured under various conditions induced by mechanical and pharmacological interventions. Renal oxygen consumption and acetate turnover varied on a wide range from 0.05 to 0.29 mmol min−1 (>5-fold) and from 0.025 to 0.188 minutes−1 (>7-fold), respectively. Acetate turnover was very significantly correlated with renal oxygen consumption (P<0.0001; R=0.82) and tubular sodium reabsorption (P=0.001; R=0.67). This study demonstrates that acetate turnover measures renal oxidative metabolism noninvasively and quantitatively, consistent with changes in tubular sodium reabsorption. This method may be applied to assess oxidative metabolism in animal models and in humans.

Estimated or Measured GFR in Living Kidney Donors Work-up?

The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web‐based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD‐EPI) and on MDRD‐eGFR. GFR was measured using 51Cr‐ ethylene‐diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 ± 11.6 years). The web‐based tool was used to predict those with mGFR < 80 mL/min/1.73 m2. Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web‐based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2. The positive predictive value was 0.19. A CKD‐EPI‐eGFR threshold of 104 mL/min/1.73 m2 and an MDRD‐eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2. We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web‐based application to identify potential donors who should benefit from GFR measurement.

Grossesse en insuffisance rénale terminale : épidémiologie, prise en charge et pronostic

Pregnancy in patients presenting end-stage renal disease is rare and there are currently no recommendations for the management of these patients. In hemodialysis patients, reduced fertility and medical reluctance limit the frequency of pregnancies. Although the prognosis has significantly improved, a significant risk for unfavorable maternal (pre-eclampsia, eclampsia) and fetal (pre-term birth, intrauterine growth restriction, still death) outcome still remains. Increasing dialysis dose with the initiation of daily dialysis sessions, early adaptation of medications to limit teratogenicity and management of chronic kidney disease complications (anemia, hypertension) are required. A tight coordination between nephrologists and obstetricians remains the central pillar of the care. In peritoneal dialysis, pregnancy is also possible with modification of the exchange protocol and reducing volumes.

Renal Involvement in Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) Syndrome: A Case Report

We report a case of a patient who had the mitochondrial cytopathy complex of neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome diagnosed at age 11 years with a biopsy-proven kidney involvement that progressed to end-stage renal disease at age 21 years. Mutations of mitochondrial DNA (mtDNA) are maternally inherited and lead to mitochondrial cytopathies with predominant neurologic manifestations: psychomotor retardation, epilepsy, ataxia, neuropathy, and myopathy. Given the ubiquitous nature of mitochondria, cellular dysfunction can also appear in tissues with high metabolic turnover; thus, there can be cardiac, digestive, ophthalmologic, and kidney complications. Mutations in the MT-ATP6 gene of mtDNA have been shown to cause NARP syndrome without renal involvement. We report a patient who had NARP syndrome diagnosed at age 11 years in whom glomerular proteinuria was present very early after diagnosis. Although neurologic manifestations were stable over time, he developed worsening proteinuria and kidney function. He started dialysis therapy at age 21 years. Kidney biopsy confirmed the mitochondrial cytopathy histologically, with abnormal mitochondria seen on electron microscopy. The MT-ATP6 gene mutation was detected in the kidney biopsy specimen.

Apport de la tomodensitométrie par rayons X dans l’évaluation de la performance rénale

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered.

Longitudinal assessment of renal function in native kidney after bariatric surgery

The epidemic of obesity parallels that of chronic kidney disease (CKD). Obesity worsens the course of CKD, mainly defined by an abnormal glomerular filtration rate (GFR). Patients with severe obesity stages (II and III with body mass index >35 kg/m2) are eligible for bariatric surgery (BS), which is the most efficient method of achieving durable weight loss. BS may reverse glomerular hyperfiltration and albuminuria, improve adipocytokine profile, and relieve diabetes and hypertension. Obesity remission after BS might prevent the progression of renal failure in populations with morbid obesity. However, evidence for the beneficial effect of BS on renal function is scant. This lack of knowledge is mainly due to methodologic reasons, which are addressed in this review. The reversibility of hyperfiltration due to the presence of functional renal reserve hampers the interpretation of changes in true GFR after BS. This true GFR is only obtained with the renal clearance of an exogenous filtration marker. Estimation of GFR is generally provided by prediction equations, namely by modification of diet in renal diseases or by chronic kidney disease-epidemiology collaborative group. These equations are not accurate because the serum levels of both creatinine and cystatin C depend on extrarenal factors, which are modified by BS. Comparing the slopes of measured GFR according to various durations of exposure with morbid obesity would be critical in providing reliable data. Herein, we review the current knowledge on the effects of BS on kidney function; we specify the methodologic issues and particularities of the dietary management of CKD patients to propose reliable directions for future clinical research.

Inflammation-linked adaptations in dermal microvascular reactivity accompany the development of obesity and type 2 diabetes

Background/ObjectivesThe increased prevalence of obesity has prompted great strides in our understanding of specific adipose depots and their involvement in cardio-metabolic health. However, the impact of obesity on dermal white adipose tissue (dWAT) and dermal microvascular functionality remains unclear. This study aimed to investigate the temporal changes that occur in dWAT and dermal microvascular functionality during the development of diet-induced obesity and type 2 diabetes in mice.MethodsMetabolic phenotyping of a murine model of hypercaloric diet (HCD)-induced obesity and type 2 diabetes was performed at three time points that reflected three distinct stages of disease development; 2 weeks of HCD-overweight-metabolically healthy, 4 weeks of HCD-obese-prediabetic and 12 weeks of HCD-obese-type 2 diabetic mice. Expansion of dWAT was characterized histologically, and changes in dermal microvascular reactivity were assessed in response to pressure and the vasodilators SNP and Ach.ResultsHCD resulted in a progressive expansion of dWAT and increased expression of pro-inflammatory markers (IL1β and COX-2). Impairments in pressure-induced (PIV) and Ach-induced (endothelium-dependent) vasodilation occurred early, in overweight-metabolically healthy mice. Residual vasodilatory responses were NOS-independent but sensitive to COX inhibition. These changes were associated with reductions in NO and adiponectin bioavailability, and rescued by exogenous adiponectin or hyperinsulinemia. Obese-prediabetic mice continued to exhibit impaired Ach-dependent vasodilation but PIV appeared normalized. This normalization coincided with elevated endogenous adiponectin and insulin levels, and was sensitive to NOS, COX and PI3K, inhibition. In obese-type 2 diabetic mice, both Ach-stimulated and pressure-induced vasodilatory responses were increased through enhanced COX-2-dependent prostaglandin response.ConclusionsWe demonstrate that the development of obesity, metabolic dysfunction and type 2 diabetes, in HCD-fed mice, is accompanied by increased dermal adiposity and associated metaflammation in dWAT. Importantly, these temporal changes are also linked to disease stage-specific dermal microvascular reactivity, which may reflect adaptive mechanisms driven by metaflammation.