Background Cardiorenal syndromes (CRS) are reputed to result in worse prognosis than isolated heart failure (HF) and chronic kidney disease (CKD). Whether it is true for all major outcomes over the long-term regardless of CRS chronology (simultaneous, cardiorenal and renocardiac CRS) is unknown. Methods The 5-year adjusted risk of major outcomes was assessed in this nationwide retrospective cohort study in all 385 687 with either CKD or HF (out of 5123 193 patients who were admitted in a French hospital in 2012). Results Overall, 84.0% patients had HF and 8.9% had CKD (they had similar age, sex ratio, diabetes and hypertension prevalence) while 7.1% had CRS (cardiorenal: 44.6%, renocardiac: 14.5%, simultaneous CRS: 40.8%). The incidence of major outcomes was 57.3%; 53.0%; 79.2% for death, 18.8%; 10.9%; 27.5% cardiovascular death, 52.6%; 34.7%; 64.3% for HF, 6.2%; 5.5%; 5.6% for myocardial infarction (MI), 6.1%; 5.8%; 5.3% for ischemic stroke, and 23.1%; 4.8%; 16.1% for end-stage kidney disease (ESKD) for isolated CKD, isolated HF and CRS, respectively. As compared to isolated CKD or HF, the risk of death, cardiovascular death and HF was markedly increased in CRS, the worse phenotype being cardiorenal CRS, while the increased risk of MI and ischemic stroke associated with CRS subtypes was statistically but not clinically significant. As compared to isolated CKD, the risk of ESKD was similar for cardiorenal syndrome only and marginally increased for renocardiac and simultaneous CRS. We could not find a synergy between HF and CKD on major clinical outcomes in the whole population (n = 5123 193 patients). Conclusions The additional impact of CRS vs isolated HF or CKD on long-term kidney and cardiovascular risk is highly heterogenous, depending of the event considered and CRS chronology. No synergy between HF and CKD could be demonstrated.

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<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 eGFR_CKD-EPI &#x3e;15 mL/min/1.73 m², urinary protein-to-Cr ratio &#x3c;0.3 g/mmol, hematuria, HbA1c &#x3c;7%, and diabetes duration &#x3c;5 years as predictors of NDHKD, independently from the indication group. <b><i>Conclusion:</i></b> NDHKD is frequent in T2D. Despite the association of hematuria with NDHKD, our results suggest that presence of hematuria and absence of DR are insufficient to indicate KB in the absence of concurrent atypical features. Conversely, rapid progression of proteinuria and rapid deterioration of eGFR are major signals of NDHKD.

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