CARDIORENAL SYNDROME AND COVID-19.

The purpose of this paper is to analyses the cases with cardiorenal syndrome, and the ratio of cardiovascular disease and COVID-19. Prospective methods were used to conduct this research, including the period (January 2020-December 2021). Cases of patients treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK) have been studied. The categorical variables were analyzed with the X² test and the Fisher exact test. The study included 120 patients with acute renal disease treated at the Nephrology Clinic at the University Clinical Center of Kosovo (UCCK), of which 46 (38.3%) female and 74 (61.6%) male. Of the 120 patients included in the study 4 were 18-34 years old, 8 were 35-49 years old, 30 were 50-64 years old, and 78 were > 65 years old. There is a strong link between cardiorenal syndrome and age. Regarding cardiorenal syndrome and its association with other diseases in this prospective study were found these concomitant diseases such as: diabetes mellitus type 2, secondary anemia, hypothyroidism, hyperparathyroidism, pneumonia, sepsis, ascites, mesenteric tumor, hyperkalemia, and Covid-19 Infection. There is a strong link between cardiorenal syndrome and COVID-19 Infection. In recent decades various studies have been done against the definition of cardiorenal syndrome, the understanding of pathophysiology, the use of new biomarkers that represent a new dimension in the diagnostic algorithm, and the difficulties in treating this syndrome.

Prognosis of Patients with Acute Kidney Injury due to Type 1 Cardiorenal Syndrome Receiving Continuous Renal Replacement Therapy.

INTRODUCTION: The prognosis of patients with acute kidney injury (AKI) caused by type 1 cardiorenal syndrome (CRS) requiring continuous renal replacement therapy (CRRT) is unclear. We investigated the in-hospital mortality and prognostic factors in these patients. METHODS: We retrospectively identified 154 consecutive adult patients who received CRRT for AKI caused by type 1 CRS between January 1, 2013, and December 31, 2019. We excluded patients who underwent cardiovascular surgery and those with stage 5 chronic kidney disease. The primary outcome was in-hospital mortality. Cox proportional hazards analysis was performed to analyze independent predictors of in-hospital mortality. RESULTS: The median age of patients at admission was 74.0 years (interquartile range: 63.0-80.0); 70.8% were male. The in-hospital mortality rate was 68.2%. Age ≥80 years (hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.21-2.87; p = 0.004), previous hospitalization for acute heart failure (HR, 1.67; 95% CI, 1.13-2.46; p = 0.01), vasopressor or inotrope use (HR, 5.88; 95% CI, 1.43-24.1; p = 0.014), and mechanical ventilation at CRRT initiation (HR, 2.24; 95% CI, 1.46-3.45; p < 0.001) were associated with in-hospital mortality. CONCLUSION: In our single-center study, the use of CRRT for AKI due to type 1 CRS was associated with high in-hospital mortality.

Apela inhibits systemic and renal inflammatory reactions in mice with type I cardiorenal syndrome.

This study investigated the effect of apela on renal function and anti-inflammatory effect on whole body and kidney tissue in mice with type I cardiorenal syndrome (CRS). The murine type I CRS model was established and apela was subcutaneously infused for two weeks. Cardiac and renal functions were evaluated by echocardiography and blood biochemistry, respectively. The systemic and renal inflammatory responses were examined with molecular biological and histological methods. Human renal glomerular endothelial cells (RGECs) were used to evaluate the adhesion effect of monocytes in vitro. Compared to mice from the control group (CRS + vehicle), the plasma levels of N-terminal pro-brain natriuretic peptide, blood urea nitrogen and creatinine were significantly decreased, while the mean left ventricular ejection fraction was increased in apela-treated CRS mice at the 4th week. The expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the circulation and kidney was decreased in apela-treated mice compared with control mice, and apela improved cardio-renal pathology in mice with type I CRS. Additionally, Apela significantly suppressed the expression of MCP-1, TNF-α, intercellular adhesion molecule-1 and vascular intercellular adhesion molecule-1 in RGECs induced by angiotensin II (Ang II), and inhibited the promoting effect of Ang II on the adhesion of THP-1 cells to RGECs. Western blot results showed that the expression of phosphorylated nuclear factor kappa B (phospho-NFκB) in CRS mice was increased, but the expression of phospho-NFκB was down-regulated after apela treatment. Furthermore, apela significantly inhibited the Ang II-mediated increase in phospho-NFκB expression in RGECs in vitro, but the administration of an apelin peptide jejunum receptor (APJ) inhibitor blocked the inhibitory effect of apela. This study revealed that apela improves cardiorenal function and reduces systemic and renal inflammatory response in type I CRS mice and the apela/APJ system may alleviate renal inflammatory responses by inhibiting the NFκB signalling pathway.

Catalytic iron mediated renal stress responses during experimental cardiorenal syndrome 1 ("CRS-1").

Cardiorenal syndrome I (CRS-1) denotes a state in which acute kidney injury occurs in the setting of acute heart failure (AHF). Isoproterenol (Iso) administration is widly used as an AHF model by transiently inducing extreme tachycardia, hypotension, and myocyte apoptosis and/or necrosis. To gain potential insights into renal manifestations of CRS-1, mice were subjected to the Iso-AHF model (50 mg Iso/kg), followed by renal functional and renal cortical assessments over 4 hours Iso induced acute azotemia (doubling of BUN, plasma creatinine) and significantly reduced renal plasma flow (prolonged plasma para-amino-hippurate clearance). Although no morphologic tubular injury was identified, marked increases in renal cortical 'stress markers' (NGAL, HO-1, IL-6, MCP-1 mRNAs) and oxidant stress (decreased glutathione, increased malondialdehyde) were observed. These changes were catalytic Fe dependent, given that the iron chelator desferrioxamine (DFO) significantly blunted, or completely reversed, these renal cortical abnormalities. Despite these acute changes, no lasting renal injury was observed (assessed over 3 days). To determine whether Iso directly impacts tubular cell integrity, cultured proximal tubule (HK-2) cells were exposed to Iso. Substantial Fe dependent cell injury (decreased MTT uptake), and Fe independent increases in HO-1/IL-6 mRNA expression were observed. We conclude that Iso-induced AHF is a useful reversible model of CRS-1. Despite its largely hemodynamic ('pre-renal') nature, Fe-mediated oxidative stress and pro-inflammatory reactions are induced. These arise, at least in part, from direct Iso- induced tubular cell toxicity, rather than simply being secondary to Iso-mediated hemodynamic events. Finally, Iso-triggered renal cytokine production can potentially contribute to 'organ cross talk' and a systemic pro-inflammatory state.

Exploring the Complexity of Death-Censored Kidney Allograft Failure.

BACKGROUND: Few studies have thoroughly investigated the causes of kidney graft loss (GL), despite its importance. METHODS: A novel approach assigns each persistent and relevant decline in renal function over the lifetime of a renal allograft to a standardized category, hypothesizing that singular or multiple events finally lead to GL. An adjudication committee of three physicians retrospectively evaluated indication biopsies, laboratory testing, and medical history of all 303 GLs among all 1642 recipients of transplants between January 1, 1997 and December 31, 2017 at a large university hospital to assign primary and/or secondary causes of GL. RESULTS: In 51.2% of the patients, more than one cause contributed to GL. The most frequent primary or secondary causes leading to graft failure were intercurrent medical events in 36.3% of graft failures followed by T cell-mediated rejection (TCMR) in 34% and antibody-mediated rejection (ABMR) in 30.7%. In 77.9%, a primary cause could be attributed to GL, of which ABMR was most frequent (21.5%). Many causes for GL were identified, and predominant causes for GL varied over time. CONCLUSIONS: GL is often multifactorial and more complex than previously thought.

Sacubitril-Valsartan Improves Anemia of Cardiorenal Syndrome (CRS).

BACKGROUND AND AIMS: Anemia is a common complication of heart failure and Chronic Kidney Disease (CKD). Sacubitril-valsartan is a novel therapy for the treatment of chronic Heart Failure with a reduced Ejection Fraction (HFrEF). We have evaluated the short-term effects of sacubitril- valsartan on the anemia of CRS. METHODS: The study group comprised 39 patients with HFrEF, who were followed-up for three months. The study is a retrospective analysis of clinical data. Data of 3 months' and baseline visits were recorded including plasmatic creatinine, glomerular filtration rate, cystatin C, kaliemia, haemoglobin, pro-BNP, and albuminuria. RESULTS: In all, 34 patients ended the follow-up. Mean sacubitril-valsartan dosage at baseline was 101 ± 62 mg/day and 126 ± 59 mg/day at end. Mean hemoglobin increased from 12.2 ± 1.1 g/dl at baseline to 12.9 ± 1.0 g/dl (p = 0.001,). Prevalence of anemia was 64.7% (95%CI, 47.9-78.5%) at baseline and 38.4 (95%CI, 23.9-55.0%) after the follow-up (p = 0.016). Serum cystatin C levels decreased from 2.71 ± 1.0 to 2.48 ± 1.0 mg/l (p = 0.028). Serum K levels remained unchanged (baseline 4.94 ± 0.60, three months visit 4.94 ± 0.61 mmol/l, p = 0.998). CONCLUSION: Sacubitril-valsartan improves anemia in CRS patients. An improvement in serum cystatin levels was observed. Few untoward effects were detected. These findings should be confirmed in wider clinical trials.

Role of GILZ in the Kidney and the Cardiovascular System: Relevance to Cardiorenal Complications of COVID-19.

Glucocorticoids are extensively used for a variety of conditions, including those associated with dysregulation of immune and inflammatory responses as primary etiopathogenic factors. Indeed, the proinflammatory cytokine storm of coronavirus disease 2019 (COVID-19) is the latest condition for which the use of a glucocorticoid has been advocated. Recognition of serious adverse effects of glucocorticoids has led to research aimed at unraveling molecular basis by which they impact immune and inflammatory events with the ultimate objective of devising novel therapies to circumvent glucocorticoids-related adverse outcomes. Consequently, glucocorticoid-induced leucine zipper (GILZ) protein was discovered and is increasingly recognized as the pivotal regulator of the effects of glucocorticoids on immune and inflammatory responses. Importantly, the advent of GILZ-based options raises the prospect of their eventual therapeutic use for a variety of conditions accompanied with dysregulation of immune and inflammatory responses and associated target organ complications. Thus, the objective of this minireview is to describe our current understanding of the role of GILZ in the cardiovascular system and the kidney along with outcome of GILZ-based interventions on associated disorders. This information is also of relevance for emerging complications of COVID-19. SIGNIFICANCE STATEMENT: Glucocorticoid-induced leucine zipper (GILZ) was initially discovered as the pivotal mediator of immune regulatory/suppressive effects of glucocorticoids. Since the use of glucocorticoids is associated with serious adverse effects, GILZ-based formulations could offer therapeutic advantages. Thus, this minireview will describe our current understanding of the role of GILZ in the kidney and the cardiovascular system, which is of relevance and significance for pathologies affecting them, including the multiorgan complications of coronavirus disease 2019.

Acute Cardiorenal Syndrome: Models and Heart-Kidney Connectors.

Cardiorenal syndrome type 1 (CRS-1) is an acute kidney injury (AKI) due to acute worsening of cardiac function. More than 20% of patients with acute heart failure develop AKI, and AKI predicts poor outcome. Although a number of potential pathways have been suggested as heart-kidney connectors which might drive the syndrome, there are significant barriers to investigation, such as a paucity of animal models, a lack of specific biomarkers, and an inconsistent temporal and causal relationship between changes in cardiac flow and development of renal dysfunction. Thus, mechanisms of heart-kidney interaction are still unclear, and there is no specific or effective therapy for CRS-1. This review, therefore, focuses on mitigating these challenges in the investigation of CRS-1. We review the available models and focus on mechanistic insights gained from those models. In particular, we focus on non-flow and endocrine mediators of CRS-1 such as heart-derived messengers which alter renal function and which may represent targetable pathways in this syndrome. As precise connectors of heart-kidney interaction remain unclear, the establishment of animal and relevant cell-culture models and further investigation are required.

Plasma Lipopolysaccharide Concentrations in Cardiorenal Syndrome Type 1.

BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1. METHODS: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers. RESULTS: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission. CONCLUSION: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1.

Lipopolysaccharide in systemic circulation induces activation of inflammatory response and oxidative stress in cardiorenal syndrome type 1.

BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury. In this study, we evaluate the role of lipopolysaccharide (LPS) and various inflammatory markers in the developing acute kidney injury (AKI) in acute heart failure (AHF) patients. METHODS: We enrolled 31 AHF patients and 20 CRS type 1 (the cause of AKI was presumed to be related to cardiac dysfunction) and 17 healthy volunteers without AHF, AKI or CKD, as control group (CTR). We assessed levels of LPS, proinflammatory cytokines (TNF-α, IL-6, IL-18), and oxidative stress marker (myeloperoxidase, MPO). RESULTS: We observed a significant increase in LPS, TNF-α, IL-6, IL-18 and MPO levels in CRS type 1 and AHF group compared to CTR. LPS levels resulted significantly higher in CRS type 1 patients compared with AHF (118.2 pg/mL, IQR 77.8-217.6 versus 13.5 pg/mL, IQR 12.0-17.0, p = 0.008). We found a cytokines and oxidative stress dysregulation in CRS type 1 patients compared with AHF. Furthermore, we observed a strong positive significant correlation between LPS levels and IL-6 (Spearman's rho = 0.79, p < 0.001), and IL-18 (Spearman's rho = 0.77, p < 0.001) and MPO (Spearman's rho = 0.80, p < 0.001), all confirm by simple linear regression analysis. CONCLUSION: CRS type 1 patients presented an increased level of LPS, pro-inflammatory cytokines, and MPO. Furthermore, there is a direct correlation between LPS and pro-inflammatory cytokines and stress oxidative marker. LPS may play a role in the pathophysiology of CRS type 1 inducing inflammation, oxidative stress and finally kidney damage.

Levels of Proinflammatory Cytokines, Oxidative Stress, and Tissue Damage Markers in Patients with Acute Heart Failure with and without Cardiorenal Syndrome Type 1.

BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Inflammation and oxidative stress seem to play a pivotal role in its pathophysiology. In this in vivo study, we examined the putative role of inflammation and humoral markers in the pathogenesis of the CRS type 1. METHODS: We enrolled 53 patients with acute heart failure (AHF); 17 of them developed AKI (CRS type 1). The cause of AKI was presumed to be related to cardiac dysfunction after having excluded other causes. We assessed the plasma levels of proinflammatory cytokines (TNF-α, IL-6, IL-18, sICAM, RANTES, GMCSF), oxidative stress marker (myeloperoxidase, MPO), brain natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in AHF and CRS type 1 patients. RESULTS: We observed a significant increase in IL-6, IL-18, and MPO levels in CRS type 1 group compared to AHF (p < 0.001). We found higher NGAL at admission in the CRS type 1 group compared to the AHF group (p = 0.008) and a positive correlation between NGAL and IL-6 (Spearman's rho = 0.45, p = 0.003) and between IL-6 and BNP (Spearman's rho = 0.43, p = 0.004). We observed lower hemoglobin levels in CRS type 1 patients compared to AHF patients (p < 0.05) and inverse correlation between hemoglobin and cytokines (IL-6: Spearman's rho = -0.38, p = 0.005; IL-18: Spearman's rho = -0.32, p = 0.02). CONCLUSION: Patients affected by CRS type 1 present increased levels of proinflammatory cytokines and oxidative stress markers, increased levels of tissue damage markers, and lower hemoglobin levels. All these factors may be implicated in the pathophysiology of CRS type 1 syndrome.

Malnutrition is prevalent in patients with cardiorenal syndrome and negatively influences clinical outcome.

Cardiorenal syndrome (CRS) describes the concurrent failure of cardiac and renal function, each influencing the other. Malnutrition and cachexia frequently develop in patients with heart failure or kidney failure. However, no information is currently available on the prevalence of malnutrition in CRS patients. We studied CRS patients admitted to an internal medicine ward during a 5-month period and evaluated their clinical characteristics and nutritional status. Malnutrition risk was assessed by using the validated screening tool NRS-2002 whilst body composition was assessed by bioimpedance analysis and muscle function was measured by handgrip (HG) strength. Cardiac mass was also recorded. Length of stay, hospital readmission and 6-month mortality were registered. During the study period, 22 CRS patients were studied. Twenty patients were diagnosed with either CRS type 1 or CRS type 5. In CRS patients, fat-free mass showed a trend toward representing a protective factor for 6-month mortality (OR=0.904; p=0.06). Also, fat-free mass correlated with HG strength and cardiac ejection fraction. Malnutrition risk was diagnosed in 45% of the patients, whereas 8 patients met the definition of cachexia. Even without statistical significance, CRS patients with malnutrition had lower BMI (Body Mass Index) (p=0.038) and fat-free mass (p= n.s.). However, CRS malnutrition was associated to higher 6-month mortality (p= 0.05), and appears to negatively influence the outcome in CRS (OR= 9; p= 0.06). Our results show that malnutrition is prevalent in CRS patients and influences the clinical outcome. The assessment of nutritional status, and particularly body composition, should be implemented in daily practice of patients with CRS.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-ß and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-ß1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Anesthesia for Patients with Concomitant Cardiac and Renal Dysfunction.

Renal disease and cardiovascular disease are commonly encountered in the same patient. The dynamic interactions between renal disease and cardiovascular disease have an impact on perioperative management. Renal failure is an independent risk factor for cardiovascular disease and the link between the two disease states remains to be fully elucidated.

Identifying evidence of cardio-renal syndrome in patients with Duchenne muscular dystrophy using cystatin C.

Patients with Duchenne muscular dystrophy (DMD) develop dilated cardiomyopathy and are at risk for kidney injury. Creatinine based estimated glomerular filtration rate (eGFR) is limited by low muscle mass with low serum creatinine levels in DMD. We assessed the relationship between cardiac function, modified Schwartz eGFR and cystatin C eGFR in patients with DMD. Ninety-three patients with DMD were screened for renal dysfunction in an outpatient neuromuscular clinic. Patients with new nephrotoxic medications, recent hospitalization or decompensated heart failure were excluded from the analysis. Eleven (12%) patients had evidence of renal dysfunction identified by cystatin C eGFR, while no patients had renal dysfunction by Schwartz eGFR. There was no significant correlation between cystatin C eGFR and age (r = -0.2, p = 0.11), prednisone dose (r = 0.06, p = 0.89) or deflazacort dose (r = -0.01, p = 0.63). There was a significant correlation between left ventricular ejection fraction and cystatin C GFR among patients with chronic left ventricular dysfunction (r = 0.46, p < 0.01), but not normal function (r = -0.07, p = 0.77). There was no significant correlation between left ventricular ejection fraction and Schwartz eGFR among patients with (r = 0.07, p = 0.59) or without (r = -0.27, p = 0.07) chronic left ventricular dysfunction. Cystatin C eGFR correlates with cardiac dysfunction in patients with DMD, thus providing novel evidence of cardio-renal syndrome in this population. Routine monitoring of renal function is recommended in patients with DMD.

Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome.

BACKGROUND AND OBJECTIVES: A major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: In this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients). RESULTS: After multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P<0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation. CONCLUSIONS: uAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.

Cardiorenal syndrome type 5: in vitro cytotoxicity effects on renal tubular cells and inflammatory profile.

Background. Cardiorenal Syndrome Type 5 (CRS Type 5) reflects concomitant cardiac and renal dysfunctions in the setting of a wide spectrum of systemic disorders. Our aim was to study in vitro effects of CRS Type 5 plasma on renal tubular cells (RTCs), in terms of cellular death and the characterization of inflammatory plasma profile in these patients. Material and Methods. We enrolled 11 CRS Type 5 patients from ICU and 16 healthy controls. Plasma from patients and controls was incubated with renal tubular cells (RTCs) and cell death was evaluated. Plasma cytokines were detected. Results. RTCs incubated with CRS Type 5 plasma showed significantly higher apoptosis and necrosis with respect to controls. Plasma cytokine profile of CRS Type 5 patients was significantly different from controls: we observed the production of pro- and anti-inflammatory mediators in these patients. Caspase-3, caspase-8, and caspase-9 were activated in cells treated with CRS Type 5 plasma compared to controls. Conclusions. Our results underline the cytotoxic effect of CRS Type 5 mediators on RTC viability, probably due to the activation of both intrinsic and extrinsic pathways of apoptosis and to the deregulation of cytokine release. The consequence may be the damage of distant organs which lead to the worsening of condition of patients.

Acute renal failure in diabetes mellitus.

OBJECTIVE: To study the causes and outcome of Acute renal failure (ARF) in diabetes mellitus. METHODS: This prospective study was conducted at nephrology unit of SIUT Karachi, Pakistan from November 2012 to May 2013. All adult patients with known underlying diabetes presenting with suspected ARF were included in the study. The treatment options were conservative and dialysis. Renal biopsy was performed in selected patients. All patients were followed for a period of six weeks for outcome of renal failure i.e. recovery, dialysis dependency and death. RESULTS: A total of 95 patients with suspected ARF were enrolled during this period. We found sepsis as the single most common factor causing ARF in 66 (69.5%) patients and the most common focus of infection was found to be urinary tract in 47 (71.2%) patients. Other factors leading to ARF included volume depletion in 19 (20%), cardio renal in 13 (13.7%), acute glomerulonephritis in 3 (3.15%) and contrast exposure in 2 (2.1%) patients. In all 72 (75.8%) patients required dialysis, while 23 (24.2%) were managed conservatively. Eventually 62 (67.39%) patients recovered, 14 (15.21%) became dialysis dependent, and 16 (17.39%) died. Among those who expired, all underwent dialysis and sepsis was the leading cause of death in 13 (81.25%) patients. CONCLUSION: Infection, especially of urinary tract is the leading cause of ARF in Diabetics. Outcome is favourable in those who dot require dialysis.

Oxidative stress: dual pathway induction in cardiorenal syndrome type 1 pathogenesis.

Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P < 0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis.