COVID-19 and kidney: role of SARS-CoV-2 infection in the induction of renal damage.

OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.

Literature review on the cross-link between ocular and renal disease: renin angiotensin aldosterone system is a main actor.

OBJECTIVE: Chronic kidney disease (CKD) and ocular disease share several cardiovascular risk factors as well as pathogenetic mechanisms having Renin-Angiotensin-Aldosterone System (RAAS) as main actor. Moreover, kidney and eyes have common genetic and embryonic origin. In this literature review, we present main evidence supporting this association for early identifying diseases affecting both systems and evaluating potential multi-target therapeutic strategies. MATERIALS AND METHODS: We performed a literature review of the current peer-reviewed English-language randomized controlled studies (RCTs), reference lists of nephrology or ophthalmology textbooks, review articles and relevant studies with ocular or eye and kidney or renal diseases as keywords until March 2020. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. RESULTS: We evaluated a total of 683 records, finally selecting 119 articles related to ocular and renal diseases. Records were divided into two areas: chronic and acute kidney disease and ocular or eye diseases. Some of the examined studies were discarded for population biases/intervention or deemed unfit. CONCLUSIONS: Based on our results, we conclude that there is evidence of a clear association between kidney and eye diseases, being this cross-link mainly based on RAAS dysregulation. Our review suggests that it may be useful to screen CKD patients for associated ocular diseases, such as cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. A comprehensive study of CKD and proteinuric patients should include careful eye examination. Renal impairment in young patients should prompt a search for ocular disease, such as TUNA syndrome or oculo-renal syndrome, in particular if family history of concurrent ocular and renal disease is present. Anti-RAAS agents are mostly recommended in patients with renal and ocular impairment.

Screening of QTc interval and global autonomic activity in autosomal dominant polycystic kidney disease and atherosclerotic renal artery stenosis hypertensive patients.

OBJECTIVE: Arterial hypertension (AH) represents a major risk factor for cardiovascular disease and is associated to several complications, such as prolonged corrected QT (QTc) interval and impaired heart rate variability (HRV). Secondary causes of AH include autosomal dominant polycystic kidney disease (ADPKD) and atherosclerotic renal artery stenosis (ARAS), both known to be related to arrhythmic risk and autonomic imbalance. The aim of the study is to evaluate whether global autonomic activity and QTc interval differently affect ADPKD and ARAS hypertensive patients. PATIENTS AND METHODS: An observational study was performed on 59 patients: 16 ADPKD patients and 19 diagnosed with ARAS, compared to 24 healthy controls (HC). All patients underwent clinical evaluation, biochemical lab tests, 24-hour electrocardiogram (ECG) and renal Doppler ultrasound. HRV was assessed through the analysis of 24-hour ECG to detect standard deviation of normal-to-normal RR intervals (SDNN). QTc interval was defined as prolonged when > 440 msec. RESULTS: SDNN was significantly lower in ADPKD and ARAS patients than HC (p < 0.0001) and no significant differences were found between ADPKD and ARAS patients (p > 0.05). QTc was found significantly higher in ARAS patients than HC (p = 0.001) and in ARAS patients than ADPKD patients (p = 0.004). CONCLUSIONS: The pathogenesis of hypertension in ADPKD and ARAS patients is related to the activation of the renin angiotensin aldosterone system (RAAS). In ADPKD, cyst enlargement leads to kidney ischemia and renin release, associated to endothelial dysfunction, low nitric oxide and sympathetic tone activation. Differently, reduction in renal perfusion pressure activates RAAS and renal adrenergic nerves in ARAS patients. We can speculate that prolonged QTc interval is more present in ARAS vs. ADPKD hypertensive patients due to a greater activation of RAAS. We suggest adding 24-hour HRV evaluation in association with traditional risk factors in course of ADPKD and ARAS hypertension to better stratify cardiovascular risk in these groups of patients.

Increase of renal resistive index and mineral metabolism disorder in patients with acute coronary syndrome with preserved renal function.

OBJECTIVE: Coronary artery disease is one of the first causes of death in the Western world; for this reason, it is essential to identify new, systemic, non-invasive and low-cost cardiovascular risk markers. The acute coronary syndrome includes ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI), based on ECG findings. We aimed to evaluate Renal Resistive Index (RRI) as a marker of cardiovascular risk and assess the associations with other cardiovascular risk factors (metabolic indexes, mineral metabolism disorders and endothelial dysfunction and atherosclerosis markers) in STEMI and NSTEMI patients. PATIENTS AND METHODS: Clinical, laboratory and instrumental examinations as metabolic and inflammation indexes, markers of atherosclerosis and endothelial dysfunction (renal function, mineral metabolism disorders, inflammation indexes, Intima Media Thickness (IMT), Ankle Brachial Pressure Index, Left Ventricular Mass Index, Relative Wall Thickness) were performed. RESULTS: Eighty-one patients with STEMI and NSTEMI were enrolled. We showed a significant positive correlation between RRI and age (p<0.01), intact parathyroid hormone (p<0.01) and IMT (p<0.01), as well as a significant negative correlation between RRI and body surface area (BSA) (p=0.02), estimated Glomerular Filtration Rate (eGFR) (p<0.01), serum calcium (p<0.01) and 25-hydroxy-vitamin D (p=0.03). Moreover, we found a significant correlation between RRI and male patients (p<0.01), coronary artery disease history (CAD) (p=0.049), hypertension (p=0.025) and left ventricular eccentric hypertrophy (LVEH) (p=0.047). CONCLUSIONS: Our study showed an association between RRI and the main traditional and non-traditional cardiovascular risk factors involved in atherosclerosis pathogenesis, such as age, BSA, hypertension, male sex, CAD history, mineral metabolism disorders and LVEH, in patients with preserved renal function. Moreover, we found a significant correlation between RRI and eGFR, suggesting that RRI could be useful in the evaluation of both renal function and progression of renal damage, even in an early stage with a conserved or only slightly reduced kidney function. We also showed a significant correlation with some markers of systemic atherosclerosis such as IMT and LVEH. For a more precise assessment of prognosis and cardiovascular risk in patients with high cardiovascular mortality, we suggest performing a systematic RRI evaluation, considering the non-invasive nature of the procedure, its reproducibility, easy execution, and low costs.

Effects of non-invasive ventilation on renal and endothelial function in patients with respiratory failure.

OBJECTIVE: Non-invasive positive pressure ventilation (NIV) is now an indispensable safeguard in the management of many pathologies. However, sometimes the positive end-expiratory pressure (PEEP) showed harmful effects on renal function, although effects on renal hemodynamic are unclear. We aimed at evaluating the effects of NIV on renal and endothelial function, in patients with chronic or acute respiratory failure. PATIENTS AND METHODS: We performed a longitudinal, prospective, interventional study. We enrolled 17 hospitalized and non-hospitalized patients (11 males) with indication to NIV and stable hemodynamic parameters. Patients were treated with NIV and followed up at T0, at T1 (at the end of the NIV cycle) and at T2 (fifteen days after). RESULTS: 17 patients (11 males) with a mean age of 71.94 ± 14.89 years were enrolled. A significant increase in flow mediated dilation (FMD) was found (p = 0.004). We showed a significant improvement, after NIV, in the values of pH (p = 0.0002), pCO2 (p = 0.0001), pO2 (p = 0.04), lactates (p = 0.04), sO2 (p = 0.02) and in the P/F Ratio (p = 0.004). We also showed a significant reduction of serum glucose (p = 0.01) and a significant increase of serum chlorine (p = 0.047), while we did not report a significant increase of creatinine (p = 0.297) or a significant change in diuresis. CONCLUSIONS: In our study NIV has no significant effects on renal function in patients with respiratory failure. Probably these patients required low PEEP values, which were less harmful to lung parenchyma and not effective on systemic hemodynamic. Furthermore, NIV has improved endothelial function in the short term, likely by reducing oxidative stress, as improvements of the gas-analysis parameters showed. Therefore, NIV could help to reduce cardiovascular risk of patients improving endothelial function.

Autonomic dysfunction in kidney diseases.

Kidney diseases are associated with many cardiovascular risk factors, such as anaemia, inflammation and chronic volume overload. Changes in the sympathovagal balance are common findings in patients with end-stage renal disease (ESRD). In particular, sympathetic hyperactivity is linked with an increase in resting heart rate leading to myocardial hypertrophy and fibrosis. The latter increases the risk of sudden cardiac death from fatal arrythmias and therefore assessment of both sympathetic and parasympathetic tones could be clinically relevant in ESRD patients. Heart rate variability and other indices are currently used to evaluate the functionality of the autonomic nervous system. Some of these have emerged as potential diagnostic tools that can support clinical decision-making processes and therapeutic strategies in patients with renal disease, including those who are on dialysis replacement therapy. In this review, we summarize the impact and the relationships between sympathovagal disturbances and kidney diseases, replacement therapies and transplantation.