Changes in renal microcirculation in patients with nephrotic and nephritic syndrome: The role of resistive index.

BACKGROUND: Renal Resistive Index (RRI) is an important and non-invasive parameter of renal damage and it is associated with abnormal microcirculation or to a parenchymal injury. The aim of our study was to compare the RRI in a cohort of patients with renal diseases categorized in three groups: nephrotic syndrome (NS), acute nephritic syndrome (ANS) and patients with urinary abnormalities (UA). METHODS: Four hundred eighty-two patients with median age of 48 years (IQR 34-62) with indications for kidney disease were included in the study. Biochemical analyses, clinical assessment with detection of NS, ANS and UA and comorbidities were reported. Renal Doppler ultrasound with RRI was evaluated in all patients at the time of enrolment. RESULTS: NS was present in 81 (16.8 %) patients while ANS in 81 (16.8 %) and UA in 228 (47.3 %) patients. Patients with ANS showed significant higher RRI compared to both patients with NS [0.71 (IQR 0.67-0.78) vs 0.68 (0.63-0.73), p < 0.001] and UA [0.71 (0.67-0.78) vs 0.65 (0.61-0.71), p < 0.001]; RRI was higher in NS patients than in patients with UA [0.68 (0.63-0.73) vs 0.65 (0.61-0.71), p < 0.001]. Patients with ANS had significantly lower median estimated glomerular filtration rate (eGFR) compared respectively to NS and UA patients [19.7 ml/min vs 54.8 ml/min and vs 72.3 ml/min, p < 0.001], while renal length was significantly higher in patients with NS compared to both patients with ANS and UA [111.88 mm vs 101.98 mm and vs 106.15, p < 0.001]. Patients with ANS had more frequently hematuria and RRI ≥ 0.70 (p < 0.001) compared to both patients with NS and patients with UA. The multiple regression analysis, weighted for age, showed that RRI inversely correlates with eGFR (ß coefficient = -0.430, p < 0.001). CONCLUSIONS: Higher and pathological RRI were found in ANS than NS and UA. Renal resistive index in ANS reflects changes in intrarenal perfusion and microvascular dysfunction related to disease characteristics.

The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

Stem Cells in Kidney Ischemia: From Inflammation and Fibrosis to Renal Tissue Regeneration.

Ischemic nephropathy consists of progressive renal function loss due to renal hypoxia, inflammation, microvascular rarefaction, and fibrosis. We provide a literature review focused on kidney hypoperfusion-dependent inflammation and its influence on renal tissue's ability to self-regenerate. Moreover, an overview of the advances in regenerative therapy with mesenchymal stem cell (MSC) infusion is provided. Based on our search, we can point out the following conclusions: 1. endovascular reperfusion is the gold-standard therapy for RAS, but its success mostly depends on treatment timeliness and a preserved downstream vascular bed; 2. anti-RAAS drugs, SGLT2 inhibitors, and/or anti-endothelin agents are especially recommended for patients with renal ischemia who are not eligible for endovascular reperfusion for slowing renal damage progression; 3. TGF-ß, MCP-1, VEGF, and NGAL assays, along with BOLD MRI, should be extended in clinical practice and applied to a pre- and post-revascularization protocols; 4. MSC infusion appears effective in renal regeneration and could represent a revolutionary treatment for patients with fibrotic evolution of renal ischemia.

Assessment of renal microcirculation in biopsy-proven tubulointerstitial nephritis in patients with and without glomerular disease: the role of resistive index.

BACKGROUND: Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease. METHODS: 132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment. RESULTS: Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68-0.77) vs 0.64 (0.60-0.67), p < 0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68-0.77) vs 0.66 (0.60-0.71), p < 0.01]. Patients with isolated-TIN had mainly RRI ≥ 0.70 (n = 15, 65.2%) with the respect to patients with non-IgA-TIN (n = 7, 12.3%) and patients with IgAN (n = 17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r = 0.233, p < 0.01) and between RRI and eGFR (r = 0.537, p < 0.001). CONCLUSION: Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions.

Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project.

BACKGROUND AND AIM: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. METHODS AND RESULTS: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04-1.47) and CV mortality (HR:1.31, 95%CI:1.03-1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. CONCLUSIONS: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.

Renal resistive index in IgA nephropathy and renal scleroderma vasculopathy.

BACKGROUND: Renal Ultra-Sound (US) and Doppler US provide measurements which reflect changes in renal and systemic haemodynamic. The renal resistive index (RRI), obtained through the Doppler spectrum analysis of renal small arteries, is altered in several pathologic conditions. Glomerulonephritis cause minor RRI changes, while renal scleroderma vasculopathy (RSV) leads to significant RRI modifications. The aim of our study was to assess RRI in IgA nephropathy (IgAN) and RSV in a retrospective observational study and to investigate determinants of the RRI in these groups of patients. METHODS: We enrolled 61 IgAN patients [23 female, median age 41 (33-58) years] and 80 SSc patients [71 female, median age 52 (43-60) years]. RRI was evaluated in all patients at the time of enrolment. Laboratory tests and clinical assessment were evaluated in all patients. RESULTS: IgAN patients showed lower RRI values than RSV patients [0.70 (0.65-0.73) vs 0.66 (0.62-0.72), p < 0.01], while no significant difference in longitudinal length was observed. Median age was significantly lower in IgAN patients than in RSV patients [41 (33-58) vs 52 (43-60), p < 0.05] while IgAN patients showed a higher prevalence of high blood pressure than RSV patients (39.3% vs 13.8%, p < 0.01). The multiple regression analysis, weighted for age, showed that RRI inversely correlates with estimated glomerular filtration rate (ß coefficient = -0.524, p < 0.0001). CONCLUSION: Higher RRI were found in RSV patients than IgAN patients. IgAN is characterized mainly by glomerular injury, not leading to major RRI changes.

Ischemic Nephropaty: The Role of the Renal Artery Stenosis Revascularization on Renal Stem Cells.

We report the case of a 65-year-old man with acute GFR decline to 37 mL/min and uncontrolled high blood pressure. He was suspected for renovascular hypertension and underwent a renal color Doppler ultrasound scan that detected a bilateral atherosclerotic renal artery stenosis. A digital selective angiography by percutaneous transluminal angioplasty and stenting (PTRAs) was successfully performed. Blood pressure rapidly normalized, GFR increased within a few days, and proteinuria disappeared thereafter. These clinical goals were accompanied by a significant increase of circulating renal stem cells (RSC) and a slight increase of resistive index (RI) in both kidneys. This single observation suggests the need for extensive studies aimed at evaluating the predictive power of RI and RSC in detecting post-ischemic renal repair mechanisms.

Late Gadolinium Enhancement in Cardiac Magnetic Resonance Imaging Is Associated with High Renal Resistive Index in Patients with Systemic Sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. The major complications are lung fibrosis, pulmonary artery hypertension, scleroderma renal crisis, and cardiac involvement. OBJECTIVE: The aim of this study was to assess renal and cardiac involvement in asymptomatic SSc patients using renal Doppler ultrasound (RDU) and cardiac magnetic resonance (CMR). MATERIALS AND METHODS: We enrolled 26 consecutive SSc patients (21 female) according to 2013 ACR/EULAR criteria. Biochemical analysis, clinical evaluation, RDU with intrarenal hemodynamic parameters (renal resistive index [RRI], pulsatility index [PI], systolic/diastolic [S/D] ratio), and CMR with late gadolinium enhancement (LGE) were investigated at the time of enrollment. RESULTS: The median PI value was significantly (p = 0.007) higher in SSc patients with LGE than in SSc patients without LGE (1.37 [1.28-1.58] vs. 1.12 [1.06-1.26]). The median RRI value was significantly (p = 0.002) higher in SSc patients with LGE than in SSc patients without LGE (0.68 [0.65-0.73] vs. 0.64 [0.63-0.65]). The median S/D ratio was significantly (p = 0.02) higher in SSc patients with LGE than in SSc patients without LGE (3.12 [2.83-3.76] vs. 2.78 [2.64-2.84]). CONCLUSIONS: Our study, although performed on a small SSc population, showed RRI and LGE as markers of vascular and fibrotic damage. Early detection of cardiorenal involvement in SSc patients without symptoms is important to avoid further complications.

Reduction in Heart Rate Variability in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Cardiovascular disease is one of the main causes of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Autonomic dysfunction is associated with an increased risk for all cardiovascular events in the general population and can be evaluated with heart rate variability (HRV). OBJECTIVE: To evaluate HRV in ADPKD patients with mild hypertension versus hypertensive patients with organ damage and healthy controls (HC). MATERIALS AND METHODS: We have enrolled 65 patients: 21 ADPKD patients (10 males), 20 patients with hypertension (14 males), and 24 HC (10 males). Biochemical analysis, clinical evaluation, anthropometric data, intima-media thickness, 24-h ECG Holter recording, and echocardiography were investigated at the time of enrollment. RESULTS: No significant differences in HRV parameters were found between ADPKD with mild hypertension and hypertensive patients with organ damage. The median of HRV variables in time domain as SDNN (global autonomic activity) was significantly lower in ADPKD and hypertensive patients than HC (p < 0.05). In the frequency domain analysis, low frequency (LF), which mainly reflects the sympathetic component, showed higher values in ADPKD and hypertensive patients than HC during the night (p < 0.01). During the night, the sympathovagal balance, LF/high frequency (HF), showed higher values in ADPKD and hypertensive patients than HC (p < 0.0001). Conversely, LF day was lower in ADPKD and hypertensive patients than HC (p < 0.01). HF, which mainly reflects the parasympathetic component, was lower in ADPKD and hypertensive patients during the night than HC (p < 0.0001). CONCLUSIONS: HRV reduction is present in ADPKD patients with mild hypertension in the absence of organ damage. The evaluation of sympathovagal balance can provide novel information on the cardiovascular risk in ADPKD patients in addition to classical risk factors.

Prognostic Factors of Renal Involvement in Systemic Sclerosis.

BACKGROUND/AIMS: Renal involvement is common in systemic sclerosis (SSc), including asymptomatic reduction of glomerular filtration rate (GFR), increased renal resistance indices, scleroderma renal crisis (SRC) and ANCA-associated vasculitis. The aim was to evaluate type and evolution of renal involvement for a period of five years. METHODS: 121 SSc patients (100 F, 21 M) with mean age of 54.9 ± 13.8, disease duration of 9 ± 6 years, of which 62 had a diffused form and 59 limited form were enrolled. All patients were screened annually for renal function by laboratory examination, ultrasound and color Doppler ultrasound of renal arteries. RESULTS: Over the five-year observation period, 6 SRC (3 M, 3 F) occurred, four of which required dialysis. One patient developed ANCA-related proliferative glomerulonephritis and the other one acute tubular necrosis. The remaining 113 patients had a preserved renal function (serum creatinine 0.75 ± 0.24 mg/dl, GFR 93.8 ± 20 ml/min, 24h proteinuria 0.20 ± 0.15 g). Doppler indices of intrarenal arterial stiffness increased with progression of capillaroscopic damage and with presence of digital ulcers. A negative correlation was observed between estimated GFR and pulsatile index (p< 0,05, r=-0.198), resistive index(p< 0,01, r=0.267), S/D ratio (p< 0,01, r=-0.237). CONCLUSION: In SSc patients, renal function was normal for 4.1 years despite the presence of increased intrarenal arterial stiffness. SRC was observed in 4.9% of SSc patients. In SSc patients, a periodic follow-up based on clinical and laboratory evaluation, colorDoppler ultrasound and, in some cases, renal biopsy is required to evaluate renal involvement.

BMI, nephroangiosclerosis and glomerulonephritis: Is there any meeting point?

AIM: Overweight has been related to renal arteriolosclerosis and is able to modify intrarenal haemodynamics. Increasing evidence suggests an association between weight in excess and primary glomerulonephritis (GN). The aim of this study was to evaluate the relationship between nutritional status and intrarenal arterial stiffness in primary GN associated to arteriolosclerosis. We have considered the glomerular diameter (GD) as morphological parameter in overweight and obese patients. METHODS: Clinical, laboratory, anthropometric data and renal Doppler ultrasound were performed immediately before kidney biopsy. RESULTS: Primary GN was diagnosed in 92 patients. Mild arteriolosclerosis was found in 19.6% of patients, moderate in the 20.6%, severe in the 10.9% while nephroangiosclerosis was diagnosed in 8.7% of patients. A positive correlation was found between body mass index (BMI) and renal resistive index (RRI) (P < 0.01, r = 0.34). RRI were significantly higher in patients with severe arteriolosclerosis at kidney biopsy (P < 0.05). Furthermore, higher BMI (P < 0.01) was found in patients with renal arteriolosclerosis than patients without renal arteriolosclerosis (26.1 ± 4.4 kg/m2 vs. 24.4 ± 4.5 kg/m2 ). Finally, in overweight and obesity patients we found a positive correlation between maximal GD and BMI (P < 0.01) and maximal GD and RRI (P < 0.01). CONCLUSION: In overweight and obese patients affected by primary GN, it might be found not only glomerular but also renal vascular lesions. Finally, we believe that nephroangiosclerosis, in combination with weight in excess, is able to modify intrarenal haemodynamic parameters. Moreover, in response to these changes, the renal tissue morphologically promotes a GD increase regardless of the underlying GN.

Angiogenic and angiostatic factors in renal scleroderma-associated vasculopathy.

BACKGROUND: The angiogenesis in systemic sclerosis (SSc) is impaired. An imbalance of pro-angiogenic factors and angiogenesis inhibitors has been implicated in the progression of peripheral microvascular damage, defective vascular repair and fibrosis. Intrarenal resistance index are considered markers of renal vasculopathy. The aim of the study is to evaluate angiogenic and angiostatic factors (VEGF and endostatin) in SSc patients and to correlate with intrarenal hemodynamic parameters. METHODS: 91 SSc patients were enrolled in this study. Serum VEGF and endostatin levels were determined. All patients underwent a renal Doppler ultrasound RESULTS: A significant positive correlation was observed between endostatin and renal Doppler parameters (p<0.0001). A negative correlation was observed between serum levels of endostatin and eGFR (p<0.01). In SSc patients with high resistive index, serum levels of endostatin were significantly (p<0.01) higher than in SSc patients with normal resistive index. The serum levels of endostatin significantly increased with progression of nailfold videocapillaroscopy damage (p<0.01) and were significantly (p<0.05) higher in SSc patients with digital ulcers than in SSc patients without digital ulcers. CONCLUSION: This is the first study that assess in SSc patients intrarenal hemodynamic parameters and endostatin. In SSc patients, endostatin represents a marker of renal scleroderma-associated vasculopathy.

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients.

BACKGROUND: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. METHODS: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. RESULTS: The serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r=-0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA. CONCLUSIONS: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies.

Cardio-Renal Syndrome Type 4: The Correlation Between Cardiorenal Ultrasound Parameters.

Bakground/Aims: Cardiovascular diseases represent the leading causes of morbidity and mortality in patients with cronich kidney disease (CKD). The pathogenesis includes a complex, bidirectional interaction between heart and kidney termed cardiorenal syndrome type 4. The aim of study was to evaluate the association between renal and cardiovascular ultrasonographic parameters and identify early markers of cardiovascular risk. METHODS: A total of 35 patients with CKD and 25 healthy controls, were enrolled and we have evaluated inflammatory indexes, mineral metabolism, renal function, renal and cardiovascular ultrasonographic parameters. RESULTS: Tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (ePAPs) showed a statistically significant difference between CKD patients and healthy controls (p<0.001, p=0.05). Also 25 hydroxyvitaminD (25-OH-VitD), parathyroid hormone (iPTH), posphorus, serum uric acid, renal resistive index (RRI) and C-reactive protein (CRP) showed a significant difference between the two groups (p=0.002, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001). Moreover the TAPSE correlated positively with estimated glomerula filtration rate (eGFR) and negatively with RRI (p=0.05, p=0.008), while ePAPs correlated negatively with eGFR and positively with RRI (p=0.029, p<0.001). CONCLUSION: CKD can contribute to the development and progression of right ventricle dysfunction with endothelial dysfunction, inflammation and mineral metabolism disorders. Accurate assessment of right ventricular function is recommended in patients with CKD. RRI and echocardiographic parameters can be an important instrument for the diagnosis, prognosis and therapeutic assessment of cardio-renal syndrome in these patients.

Evaluation of estimated glomerular filtration rate and clinical variables in systemic sclerosis patients.

OBJECTIVES: The most important renal complication of systemic sclerosis (SSc) is scleroderma renal crisis (SRC). Many patients demonstrate less severe renal complications, most likely associated with reduced renal blood flow and a consequent reduction in glomerular filtration rate (GFR). The mechanism of this slowly progressive form of chronic renal disease is unclear. The aim of this study was to evaluate GFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the 7-variable Modification of Diet and Renal Disease (MDRD) equations in SSc patients and to correlate estimated GFR (eGFR) with clinical variables of the disease. METHODS: 105 unselected and consecutive patients with SSc were enrolled. Serum creatinine was measured in all patients and GFR was estimated by 7-variable MDRD and CKD-EPI equations. Nailfold videocapillaroscopy was performed in all patients. RESULTS: The mean value of eGFR evaluated by both 7-variable MDRD and CKD-EPI was significantly different (p < 0.0001) in the three capillaroscopic groups and correlated negatively with the severity of capillaroscopic damage (early: 95 ± 16 mL/min and 101 ± 12 mL/min, active: 86 ± 25 mL/min and 95 ± 17 mL/min, late: 76 ± 21 mL/min and 82 ± 21 mL/min). The mean value of eGFR evaluated by 7-variable MDRD (97 ± 23 mL/min vs. 74 ± 15 mL/min, p < 0.0001) and CKD-EPI< (0.83 ± 0.20 mL/min vs. 0.68 ± 0.10 mL/min, p < 0.0001) was significantly higher in SSc patients without history of digital ulcers than in those with. CONCLUSION: We can conclude that in SSc patients without renal involvement, eGFR decreases with the progression of digital vascular damage.

Iloprost infusion reduces serological cytokines and hormones of hypoxia and inflammation in systemic sclerosis patients.

INTRODUCTION: Systemic sclerosis (SSc) is characterized by microvascular damage of skin and internal organs with chronic hypoxia and release of cytokines and hormones such as neutrophil gelatinase-associated lipocalin (NGAL), fibroblast growth factor-23 (FGF-23) and Klotho. Aim of the study was to evaluate FGF-23, Klotho and NGAL serum levels in SSc patients and healthy controls (HC) and to evaluate serum levels changes of FGF-23, Klotho and NGAL after Iloprost. METHODS: Twenty-one SSc patients and 20 HC were enrolled. In SSc patients, peripheral venous blood samples were collected at the first day before the autumn Iloprost infusion (t0), 60 min (t1) and 14 days after Iloprost infusion (t2). RESULTS: SSc patients had higher serum level of FGF-23 [18.7 ± 6.4 pg/ml versus 3.6 ± 2.2 pg/ml, p < 0.001], Klotho [5.1 ± 0.8 pg/ml versus 2.3 ± 0.6 pg/ml, p < 0.001] and NGAL [20.9 ± 2.6 pg/ml versus 14.5 ± 1.7 pg/ml, p < 0.001] than HC. Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 10.4 ± 5.5 pg/ml, p < 0.001), Klotho (5.1 ± 0.8 pg/ml versus 2.5 ± 0.6 pg/ml, p < 0.001) and NGAL (20.9 ± 2.6 pg/ml versus 15.1 ± 2.3 pg/ml, p < 0.001) between t0 and t1. The Iloprost infusion reduces serum level of FGF-23 (18.7 ± 6.4 pg/ml versus 6.6 ± 5.1 pg/ml), Klotho (5.1 ± 0.8 pg/ml versus 2.3 ± 0.4 pg/ml) and NGAL (20.9 ± 2.6 pg/ml versus 15.5 ± 1.9 pg/ml) between t0 and t2. CONCLUSIONS: SSc patients had higher FGF-23, Klotho and NGAL than HC. Iloprost reduces serum levels of FGF-23, Klotho and NGAL.

Serum markers of microbial translocation and intestinal damage in assessment of gastrointestinal tract involvement in systemic sclerosis.

Gastrointestinal (GI) tract involvement affects up to 90% of Systemic sclerosis (SSc) patients. The presence of GI symptoms is assessed by the University of California, Los Angeles, and Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT 2.0). Microbial translocation (MT) is reported in SSc patients consequently to increased intestinal permeability due to intestinal damage (ID) and dysbiosis. Aim of this study was to assess circulating levels of LBP and EndoCab IgM (markers of MT), IL-6 (marker of inflammation), I-FABP and Zonulin (markers of ID) in a cohort of SSc patients and healthy controls (HC). Moreover, we aimed to correlate these parameters with severity of GI symptoms. UCLA SCTC GIT 2.0 questionnaire was administered to 60 consecutive SSc patients. Markers of MT, inflammation and ID were evaluated in SSc patients and HC. SSc patients had higher median value of markers of MT, inflammation and ID than HC. The logistic regression analysis showed LBP as the only variable associated with an UCLA total score "moderate-to-very severe" [OR 1.001 (CI 95%: 1.001-1.002), p < 0.001]. The logistic regression analysis showed LBP [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01] and disease duration [OR 1.242 (CI 95%: 1.023-1.506), p < 0.05] as variables associated with UCLA distension/bloating "moderate-to-very severe". The logistic regression analysis showed LBP as the only variable associated with UCLA diarrhea "moderate-to-very severe" [OR 1.002 (CI 95%: 1.001-1.003), p < 0.01]. SSc patients with dysregulation gut mucosal integrity expressed by high levels of MT and ID biomarkers had more severe GI symptoms.

COVID-19 Infection in Autosomal Dominant Polycystic Kidney Disease and Chronic Kidney Disease Patients: Progression of Kidney Disease.

INTRODUCTION: the COVID-19 pandemic has brought to light the intricate interplay between viral infections and preexisting health conditions. In the field of kidney diseases, patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and Chronic Kidney Disease (CKD) face unique challenges when exposed to the SARS-CoV-2 virus. This study aims to evaluate whether SARS-CoV-2 virus infection impacts renal function differently in patients suffering from ADPKD and CKD when compared to patients suffering only from CKD. MATERIALS AND METHODS: clinical data from 103 patients were collected and retrospectively analyzed. We compared the renal function of ADPKD and CKD patients at two distinct time points: before COVID-19 infection (T0) and 1 year after the infection (T1). We studied also a subpopulation of 37 patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min and affected by ADPKD and CKD. RESULTS: clinical data were obtained from 59 (57.3%) ADPKD patients and 44 (42.7%) CKD patients. At T1, ADPKD patients had significantly higher serum creatinine levels compared to CKD patients, and a significantly lower eGFR was observed only in ADPKD patients with eGFR < 60 mL/min compared to CKD patients (p < 0.01, p < 0.05; respectively). Following COVID-19 infection, ADPKD-CKD patients exhibited significantly higher variation in both median serum creatinine (p < 0.001) and median eGFR (p < 0.001) compared to CKD patients. CONCLUSION: the interplay between COVID-19 and kidney disease is complex. In CKD patients, the relationship between COVID-19 and kidney disease progression is more established, while limited studies exist on the specific impact of COVID-19 on ADPKD patients. Current evidence does not suggest that ADPKD patients are at a higher risk of SARS-CoV-2 infection; however, in our study we showed a significant worsening of the renal function among ADPKD patients, particularly those with an eGFR < 60 mL/min, in comparison to patients with only CKD after a one-year follow-up from COVID-19 infection.

Kidney Biopsy and Immuno-Rheumatological Diseases: A Retrospective and Observational Study.

Renal involvement is a common occurrence in patients with immuno-rheumatological diseases (IRDs). Several instances of glomerulonephritis (GN) occur in the setting of IRD and complicate the clinical course of an underlying condition. The aim of this study was to observe the spectrum of nephropathies according to age, kidney function, history of IRD at the time of biopsy, and histopathological kidney diagnosis. We evaluated data relating to 699 consecutive kidney native biopsies (female 52.1%) with a median age of 48 years (IQR 34-62) performed in adult patients collected over 15 years. The study population was divided into three groups: patients with kidney histological findings correlated to underlying IRD (Group 1), patients with kidney histological findings not correlated to underlying IRD (Group 2), and patients with kidney histological findings compatible with "de novo" IRD (absent in personal medical history) (Group 3). Kidney involvement related to IRD was found in 25.2% of patients. Group 1 was mostly represented by lupus nephritis (76.6%), with a younger age than Group 3 (p < 0.001) and by a higher percentage of females than other groups (p < 0.001). Group 3 was the most represented by microscopic polyangiitis (50.8%) when compared with the other two groups (p < 0.001). Acute nephritic syndrome (p < 0.001), acute kidney injury (AKI), and abnormal urinalysis (p < 0.001) were more represented in Group 3 than the other groups. In conclusion, IRDs are characterized by different clinical presentations and heterogeneous histological findings. Kidney biopsy remains fundamental to achieving the correct diagnosis and starting targeted therapy.