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Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio

Background and Aims Kidney Biopsies (KB) performed in patients with Type-2 diabetes (T2D) usually aim at differentiating diabetic nephropathy (DN) from other kidney diseases. However, KB could also help refining patients’ prognosis, both in terms of renal survival, and in terms of patient survival. In 2010, the Renal Pathology Society developed a pathological classification of DN, but the prognostic value of the described items , is still imperfectly documented. We aimed to assess the prognostic performances of these items to predict renal and patient survival. Method Native KBs with diabetic and/or hypertensive nephropathy (DN/HN) performed in patients with T2D in four French centers were analyzed and scored according to the classification developed by the Renal Pathology Society. Clinical and biological data was collected from the patients’ records. Survival analyses were performed for renal survival (time to first dialysis or preemptive transplantation) and death after dichotomization of continuous data). For each of the analyses, we first established a model comprising clinical data only. We then assessed the benefit of adding each of the pathological item to the clinical model. Finally, we performed a backward stepwise analysis to identify items predictive of renal and/or patient survival. Results We analyzed 165 biopsies with DN/HN from patients with T2D and with at least 12 months of follow-up (unless they reached an endpoint during the first year). Among them, 73 (44%) were male, 155 (94%) had hypertension, 53 (34%) hematuria, 22 (15%) had proliferative diabetic retinopathy (DR), 33 (23%) had non-proliferative DR, 90 (62%) had no DR (20 had missing data). Mean (SD) age was 63 (11), median [IQR] eGFRCKD-EPI was 29 [18;45] ml/min/1.73m², urinary protein-to-creatinine ratio was 0.38 [0.14;0.83] g/mmol, HbA1c was 7 [6.2;8.2] % and diabetes duration before KB was 10 [5;19] years. The median [IQR] follow-up was 33 months[18;57]. During the follow-up, 43 (26%) patients died and 69 (42%) required renal replacement therapy (RRT). The percentage of ischemic glomeruli, and presence of more than one area of arteriolar hyalinosis (ah=2), were predictive of renal survival and improved the predictive value of the model when added to clinical parameters. Presence of at least one convincing Kimmelstiel–Wilson lesion (nodular glomerulosclerosis or Class III DN) was predictive of death and similarly improved the predictive model (See figure). Conclusion Pathological findings on KB, as classified by the Renal Pathology Society, carry significant prognostic value in patients with T2D and DN/HN. Vascular lesions (presence of arteriolar hyalinosis and less than 7% of ischemic glomeruli) predicted the need for RRT, while nodular glomerulosclerosis was predictive of death.

International audience; No abstract available

Background and Aims Despite decades of use of low protein diets (LPD) in the management of chronic kidney disease (CKD), the mechanisms through which it delays the progression to end-stage renal disease (ESRD) remain controversial. A reduced production of uremic toxins could contribute to the benefits of the LPD. Aromatic amino-acids are precursors of major uremic toxins such as p-cresyl sulfate (PCS), indoxyl sulfate (IS), indole-3-acetic acid or phenol. We investigated the hypothesis that a low aromatic amino acid diet (LAA, namely low intake of tyrosine, tryptophan and phenylalanine) while being normoproteic, could be as effective as a LPD, through the specific diminution of uremic toxins production. Method Renal failure was chemically induced in mice with a diet containing 0.25% (w/w) of adenine. Thereafter, they received 3 different diets for 6 weeks: normoproteic diet (NPD: 14.7% proteins, aromatics 0.019%), LPD (5% proteins, aromatics 0.007%) and LAA (14% proteins, aromatics 0.007%). Results LAA and LPD had no significant effect on body weight. Plasma creatinine was significantly lower in LPD and LAA groups compared to NPD group (72 ± 4 and 73 ± 4 µmol/L vs 127 ± 6 µmol/L, p Conclusion These results suggest that LAA confers similar benefits as compared with those of LPD to delay the progression of CKD through reduction of uremic toxins production, with lower risk of malnutrition. Renal function and urinary protein excretion in control and CKD mice Serum creatinine (A), blood urea nitrogen (B) and urinary proteins (C) in control and CKD mice fed with normoproteic diet (NPD), low protein diet (LPD) or low aromatic amino-acid diet (LAA). Data are expressed as mean ± SEM for n = 5-11 animals in each group. *p

Background and Aims Diabetic Nephropathy (DN) is usually a presumptive diagnosis based on clinical and biological evidences. However, Renal Biopsies (RB) may be performed when the suspicion of Non-Diabetic Renal Disease (NDRD) with potential specific treatment arises from atypical features mainly identified through studies focusing on the power of individual clinical and biological features to predict NDRD. We aimed to assess the actual value of RB indications (RBi) to discriminate NDRD from Type 2 Diabetes (T2D) Associated Renal Disease (T2D-ARD) such as DN and Hypertensive nephropathy which are frequently associated, seen in similar patients with high cardiovascular risk, lack for specific treatment and might be therefore be considered as “failure events” in the context of RB performed to diagnose NDRD with specific treatment. Method We conducted a retrospective multicenter study in four nephrology units and reviewed the charts of patients with T2D who underwent a first RB from 2006 to 2015. Clinical and biological characteristics, RBi and diagnoses were retrospectively collected from the patients’ medical charts. RBi were defined according to the sequence in Figure 1. As such, diabetic retinopathy may be absent in patients of all indication groups, conversely, patients in group 6 and 7 had stable proteinuria and renal function. Similarly, patients with monoclonal gammopathy were all included in group 1.We considered missing data regarding the absence/presence of Diabetic Retinopathy (DR) as meaningful, suggesting the data was unneeded to reach a decision of RBi. We performed univariate and multivariate logistic regression analyses to identify clinical or biological features associated with the diagnosis of NDRD. We also compared the number and percentage of actual NDRD diagnosed for each of the RBi. Results 464 first renal biopsies were performed in 464 patients during the study period. Two RB were excluded because the RBi could not be clearly identified through careful reviewing of the patients’ medical charts. Of the 462 remaining RB, 40% revealed NDRD. The most frequent were acute interstitial nephritis, IgA nephropathy and acute tubular necrosis (8.7%, 5.8% and 4.1% respectively). Patients with NDRD were more frequently >65yo (55 vs 44%), with serum creatinine (SCr) >250 µmol/l (52 vs 30%), hematuria (58 vs 36%), non-retrieved DR status (45 vs 17%), and less frequently with urinary-to-protein ratio (UPCR) >3g/g (33 vs 57%), HbA1c >7% (32 vs 50%) and duration of diabetes >5 years (52 vs 72%).Logistic regression analyses identified high SCr, UPCR, hematuria and low diabetes duration as predictive of NDRD. Surprisingly, missing RD status rather than absence of RD was predictive of NDRD. As expected NDRDs were frequent in patient with RBi 1 to 3 (53%, 40% and 21%), infrequent in patients with RBi 5 (7%) and totally absent from patients with RBi 6 and 7 despite their predictive value as regards with NDRD. Conclusion Our study confirms several well-known facts on the subject of renal biopsy in patients with T2D: 1) Renal biopsy is useful in selected patients with T2D and renal disease to diagnose NDRD with specific treatment. 2) Hematuria and short duration of diabetes are predictive of NDRD. On the other hand, our study suggests two novel and antidogmatic findings: 1) Assessing the presence of diabetic retinopathy is not required for RBi. 2) Hematuria is not indicative of NDRD in patients with otherwise typical diabetic kidney disease. Of course, our study is limited by its retrospective design precluding us of precisely defining what was considered rapid evolution of DFG or proteinuria emphasizing the need for prospective studies.

Introduction L’interet pronostique des lesions histologiques dans la nephropathie diabetique (ND) n’est pas bien determine. En 2010, la Renal Pathology Society a developpe une classification de la ND mais la valeur pronostique des items decrits n’est pas documentee. Nous avons evalue les performances pronostiques des items de cette classification sur la survie renale. Description Les biopsies de reins natifs avec une nephropathie diabetique et/ou hypertensives realisees chez des patients diabetiques de type 2 dans quatre centres francais ont ete analysees et scores (classe et items individuels) selon la classification developpee par la Renal Pathology Society (Tervaert JASN 2010). Methodes La survie renale (transplantation preemptive ou mise en dialyse) dans les trois ans suivant la biopsie a ete analysee par une regression de Cox. Le principe de proportionalite a ete verifie par le test des residus de Schoenfeld et par verification visuelle des courbes log(-log(Survie))∼log(temps). Une premiere etape a ete la realisation d’un modele avec les donnees cliniques et biologiques. A ce modele ont ete ajoutes individuellement chacun des items histologiques. Le modele final a ete construit par une regression retrograde etape par etape. La robustesse du modele a ete testee par un modele competitif prenant en compte le deces comme risque competitif. Resultats 164 biopsies ont ete analysees avec la repartition suivante des classes : 0-1 : 7,3 %, 2a : 21,3 %, 2b :11,6 %, 3 : 37,2 % et 4 : 22,6 %. Durant les 3 ans suivant la biopsie, 51 patients (31 %) ont necessite une technique de suppleance renale. Un DFGCKD-EPI > 30, un rapport proteine/creatinine urinaire > 0,2 g/mmol et la presence de capsular drop etaient predictifs du pronostic renal ( Fig. 1 ). Les autres items histologiques, dont la classification glomerulaire, n’etaient pas associes au pronostic renal. Conclusion La classification glomerulaire de la ND de la Renal Pathology Society semble depourvue d’interet pronostic. La presence d’une Capsular drop est en revanche un marqueur de mauvais pronostic renal.

Introduction L’interet des regimes pauvres en proteines au cours de la maladie renale chronique (MRC) est toujours discute car leur action reste mal comprise. Une diminution de la production de toxines uremiques pourrait expliquer le benefice de ces regimes. Les acides amines aromatiques etant les precurseurs de nombreuses toxines uremiques telles que le p-cresyl sulfate (PCS) et l’indoxyl-sulfate (IS), nous avons teste si un regime normoproteique mais appauvri en acides amines aromatiques (tyrosine, tryptophane, phenylalanine) pourrait s’averer aussi efficace qu’un regime pauvre en proteines, en limitant la production des toxines uremiques. Methodes La MRC a ete induite chez des souris C57Bl/6 JRj par nephrectomie chimique via un regime adenine (0,25 %, 4 semaines). Elles ont ensuite recu 3 differents regimes sur une periode de 6 semaines. Regime standard (normoproteique, NPD : 14,7 % de proteines, AA aromatiques 0,019 %), regime pauvre en proteine (LPD, proteines 5 %, AA aromatiques 0,007 %) ou regime pauvre en acides amines aromatiques (LAA : proteines 14 %, AA aromatiques 0,007 %). Resultats obtenus ou attendus La creatininemie etait significativement plus basse dans le groupe LPD et LAA que dans le groupe NPD (71,6 ± 4,2 et 73 ± 3,8 μmol/L vs. 127 ± 6,3 μmol/L, p Conclusion Un regime normoproteique appauvri en acides amines aromatiques est aussi nephroprotecteur qu’un regime pauvre en proteines au cours de la maladie renale chronique, sans exposer au risque de denutrition.

Introduction Le diagnostic de nephropathie diabetique (ND) est generalement porte sur des arguments cliniques. En effet, la frequence de la ND dans la population diabetique est telle que la biopsie renale (BR), geste invasif a risque de complications graves, n’est realisee qu’en cas d’atypie dans la presentation ou d’argument pour un autre diagnostic. Patients et methodes Nous avons separe les patients diabetiques ayant eu une BR pour syndrome glomerulaire entre 2006 et 2015 dans notre service selon l’indication de la BR. Le groupe 1 (G1) comprenait les BR motivees uniquement par la presence d’une ou plusieurs atypies (absence de retinopathie diabetique [RD], presence d’une hematurie [HU], evolution rapide de la maladie renale, augmentation rapide de la proteinurie, ou syndrome nephrotique brutal) et le groupe 2 (G2) par la presence d’un ou plusieurs arguments pour un maladie renale non diabetique (MRND). Nous avons ensuite compare les frequences de ND seule et de MRND seule ou en association avec la ND et des complications de la BR. Resultats Cent quarante-quatre patients ont ete identifies, 68 dans le groupe 1 et 76 dans le groupe 2. Il n’y avait pas de difference significative entre les 2 groupes pour le genre, l’âge, la presence d’une HTA, la creatininemie, le ratio proteine/creatinine urinaire, la presence d’une hematurie, la presence d’une retinopathie, le traitement par IEC/ARAII et la duree du diabete. Les HbA1c etaient differentes (7,8 ± 2,2 dans le G1 vs. 7,1 ± 1,4 dans le G2, p = 0,036). Une ND seule etait presente chez 90 % des patients du G1 et 50 % de ceux du G2 ( p p = 0,027). Discussion Il n’y a pas de consensus concernant l’indication de la BR chez les sujets diabetiques. L’association de certains elements cliniques et/ou biologique a la presence d’une ND a ete rapportee. A l’inverse, nous avons etudie la rentabilite diagnostique de la BR chez un patient diabetique pour le diagnostic d’une MRND selon l’indication. Il est particulierement notable qu’aucun des patients biopsies pour l’absence de RD ou la presence d’HU n’avait de MRND. De plus, le taux de complication etait plus eleve dans ce groupe. Conclusion L’absence de RD ou la presence d’HU ne constituent pas une indication pour la realisation d’une BR, ce d’autant plus qu’une complication est plus probable chez ces patients.