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Background Acute kidney injury (AKI) requiring renal replacement therapy (RRT) in the ICU portends a poor prognosis. We aimed to better characterize predictors of survival and the mechanism of kidney failure in these patients. Methods Retrospective observational study using clinical and radiological electronic health records, analysed by univariable and multivariable binary logistic regression. Histopathological examination of post-mortem renal tissue was performed. Results Among 157 patients with AKI requiring RRT, higher serum creatinine at RRT initiation associated with increased ICU-survival (OR 0.33, 95%CI 0.17–0.62, p = 0.001) however, muscle mass (a marker of frailty) interacted with creatinine (p = 0.02) and superseded creatinine as a predictor of survival (OR 0.26 95%CI 0.08–0.82; p = 0.02). Achieving lower cumulative fluid balance (mls/kg) predicted ICU-survival (OR 1.01 95%CI 1.00 -1.01, p 500mls/24 hours strongly predicted successful liberation from RRT (OR 0.125, 95%CI 0.05–0.35, p Conclusions Confounding of creatinine by muscle-mass undermines its use as a marker of AKI severity in clinical studies. Volume management and urine-output are key determinants of outcome. Loss of synaptopodin implicates glomerular injury in the pathogenesis of S-AKI.

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.

Background The coronavirus disease 2019 (COVID-19) may be associated with kidney injury, which may impact patient's prognosis. Methods We report a multicentric retrospective case series of patients with COVID-19 who developed acute kidney injury (AKI) and/or proteinuria and underwent a kidney biopsy in Paris and its metropolitan area. Results Forty-seven patients (80.9% men) with COVID-19 who underwent a kidney biopsy between 8 March and 19 May 2020 were included. The median age was 63 years (interquartile range 52–69). Comorbidities included hypertension (66.0%), diabetes mellitus (27.7%), obesity (27.7%), history of chronic kidney disease (25.5%), cardiac diseases (38.6%) and respiratory diseases (27.3%). Initial symptoms were fever (85.1%), cough (63.8%), shortness of breath (55.3%) and diarrhoea (23.4%). Almost all patients developed AKI (97.9%) and 63.8% required renal replacement therapy. Kidney biopsy showed two main histopathological patterns, including acute tubular injury in 20 (42.6%) patients, and glomerular injury consisting of collapsing glomerulopathy (CG) and focal segmental glomerulosclerosis in 17 (36.2%) patients. Two (4.3%) patients had acute vascular nephropathy, while 8 (17%) had an alternative diagnosis most likely unrelated to COVID-19. Acute tubular injury occurred almost invariably in the setting of severe forms of COVID-19, whereas patients with glomerular injury had various profiles of COVID-19 severity and CG was only observed in patients harbouring a combination of APOL1 risk variants. At the last follow-up, 16 of the 30 patients who initially required dialysis were still on dialysis, and 9 had died. Conclusions This study describes the spectrum of kidney lesions in patients with COVID-19. While acute tubular injury is correlated with COVID-19 severity, the pattern of glomerular injury is intimately associated with the expression of APOL1 risk variants.

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.

Acute kidney injury (AKI) is a major complication in patients with cancer, associated with significant morbidity and mortality. Only two cases of kidney lymphangitic carcinomatosis associated with AKI have been reported, in gastric and colorectal adenocarcinoma. Here, we report on a 53-year-old man with pancreatic adenocarcinoma who developed AKI as a result of kidney lymphangitic carcinomatosis. The patient rapidly became anuric and required haemodialysis. Kidney lymphangitic carcinomatosis should be considered as a cause of AKI in patients with cancer and may become a more frequent clinical finding as patients with metastatic carcinoma survive for longer.