Urinary C3 levels associated with sepsis and acute kidney injury—A pilot study

Acute kidney injury (AKI) is an abrupt deterioration of renal function often caused by severe clinical disease such as sepsis, and patients require intensive care. Acute-phase parameters for systemic inflammation are well established and used in routine clinical diagnosis, but no such parameters are known for AKI and inflammation at the local site of tissue damage, namely the nephron. Therefore, we sought to investigate complement factors C3a/C3 in urine and urinary sediment cells. After the development of a C3a/C3-specific mouse monoclonal antibody (3F7E2), urine excretion from ICU sepsis patients was examined by dot blot and immunoblotting. This C3a/C3 ELISA and a C3a ELISA were used to obtain quantitative data over 24 hours for 6 consecutive days. Urine sediment cells were analyzed for topology of expression. Patients with severe infections (n = 85) showed peak levels of C3a/C3 on the second day of ICU treatment. The majority (n = 59) showed C3a/C3 levels above 20 μg/ml at least once in the first 6 days after admission. C3a was detectable on all 6 days. Peak C3a/C3 levels correlated negatively with peak C-reactive protein (CRP) levels. No relationship was found between peak C3a/C3 with peak leukocyte count, age, or AKI stage. Analysis of urine sediment cells identified C3a/C3-producing epithelial cells with reticular staining patterns and cells with large-granular staining. Opsonized bacteria were detected in patients with urinary tract infections. In critically ill sepsis patients with AKI, urinary C3a/C3 inversely correlated with serum CRP. Whether urinary C3a/C3 has a protective function through autophagy, as previously shown for cisplatin exposure, or is a by-product of sepsis caused by pathogenic stimuli to the kidney must remain open in this study. However, our data suggest that C3a/C3 may function as an inverse acute-phase parameter that originates in the kidney and is detectable in urine.

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Cytomegalovirus in urinary sediment in patients with acute kidney injury

BMC Nephrology ◽

10.1186/s12882-021-02377-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sahra Pajenda ◽

Sebastian Kapps ◽

Daniela Gerges ◽

Gregor Hoermann ◽

Ludwig Wagner ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Allograft ◽

Quantitative Polymerase Chain Reaction ◽

Rna Extraction ◽

Kidney Injury ◽

Solid Organ ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Urine Sediment ◽

Urinary Sediment

Abstract Background Immunosuppression in solid organ transplantation is associated with frequent infections. Renal allograft recipients are susceptible to opportunistic infections and can acquire human cytomegalovirus (HCMV) infections even within the allograft. There, HCMV can be found in both the glomerulus and tubular cells, but is mostly restricted to specific and circumscribed sites. Therefore, not all organ infections are identifiable by immunohistology for HCMV proteins in fine needle core biopsies. Thus, we performed a urinalysis study to search for HCMV-specific RNA transcripts in the urine sediment of patients with acute kidney injury. Methods Urinary sediment of 90 patients with acute kidney injury (AKI), including 48 renal transplant recipients (RTX) and 42 non-transplant recipients (nRTX), was collected from morning urine for RNA extraction and reverse transcription. The copy number of HCMV transcripts was evaluated using a UL132 HCMV-specific probe set and by real-time quantitative polymerase chain reaction (RT-qPCR). Results Of the 48 RTX patients, ten showed HCMV copies in their urine sediment cells. Within this group, three recipients had negative HCMV serology and received an allograft from an HCMV-seropositive donor. In addition, all three RTX patients on a belatacept-based immunosuppressive regimen had HCMV transcripts in their urine. Of the 42 nRTX patients, only two had detectable HCMV transcripts in urine sediment cells and both were under immunosuppression. Conclusions Ten immunosuppressed renal allograft recipients and two immunosuppressed non-transplant patients with AKI showed HCMV copies in urine sediment. Thus, HCMV positivity in urinary sediment appears to be associated with immunosuppression. This study describes a novel noninvasive method for detection of HCMV in urinary sediment. Whether all HCMV infections can be detected or only those with viral replication warrants further investigation.

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Preoperative hemoglobin and uric acid levels as risk factors for acute kidney injury in cardiac surgery patients

Medicinski pregled ◽

10.2298/mpns2002005g ◽

2020 ◽

Vol 73 (1-2) ◽

pp. 5-12

Author(s):

Miodrag Golubovic ◽

Andrej Preveden ◽

Ranko Zdravkovic ◽

Jelena Vidovic ◽

Bojan Mihajlovic ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Uric Acid ◽

Cardiac Surgery ◽

Kidney Injury ◽

C Reactive Protein ◽

Reactive Protein ◽

Preoperative Hemoglobin ◽

Significant Difference ◽

Acute Kidney Injury Development

Introduction. Acute kidney injury associated with cardiac surgery is a common and significant postoperative complication. With a frequency of 9 - 39% according to different studies, it is the second most common cause of acute kidney injury in intensive care units, and an independent predictor of mortality. This study aimed to investigate the importance of preoperative hemoglobin and uric acid levels as risk factors for acute kidney injury in the postoperative period in cardiac surgery patients. Material and Methods. The study included a total of 118 patients who were divided into two groups. Each group included 59 patients; the fist group included patients who developed acute kidney injury and required renal replacement therapy, and the second included patients without acute kidney injury. Types of cardiac surgery included coronary, valvular, combined, aortic dissection, and others. All necessary data were collected from patient medical records and the electronic database. Results. A statistically significant difference was found between the groups in preoperative hemoglobin levels (108.0 vs. 143.0 g/l, p = 0.0005); postoperative urea (26.4 vs. 5.8 mmol/l, p = 0.0005) and creatinine (371.0 vs. 95.0 ?mol/l, p = 0.0005), acute phase inflammatory reactants C-reactive protein (119.4 vs. 78.9 mg/l, p = 0.002) and procalcitonin (7.0 vs. 0.2 ng/ml, p = 0.0005), creatine kinase myocardial band isoenzyme (1045.0 vs. 647.0 mg/l, p = 0.014); duration of extracorporeal circulation (103.5 vs. 76.0 min, p = 0.0005) and ascending aortic clamp during cardiac surgery (89.0 vs. 67.0 min, p = 0.0005). The exception was the preoperative uric acid level, where there was no statistically significant difference (382.0 vs. 364.0 ?mol/l, p = 0.068). There was a statistically significant correlation between the use of inotropic agents and acute kidney injury development. Conclusion. There is a correlation between the preoperative low hemoglobin levels and postoperative acute kidney injury. There is no statistically significant correlation between the preoperative levels of uric acid and postoperative acute kidney injury.

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High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm8122192 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2192 ◽

Cited By ~ 2

Author(s):

Nicola Cosentino ◽

Stefano Genovese ◽

Jeness Campodonico ◽

Alice Bonomi ◽

Claudia Lucci ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Acute Kidney Injury ◽

Kidney Injury ◽

High Sensitivity ◽

Future Research ◽

Hospital Death ◽

C Reactive Protein ◽

Reactive Protein ◽

Hs Crp

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 ± 87 vs. 16 ± 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome.

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Inflammation as a predictor of acute kidney injury and mediator of higher mortality after acute kidney injury in non-cardiac surgery

Scientific Reports ◽

10.1038/s41598-019-56615-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Miho Murashima ◽

Masatoshi Nishimoto ◽

Maiko Kokubu ◽

Takayuki Hamano ◽

Masaru Matsui ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Cox Regression ◽

Kidney Injury ◽

Mediation Effects ◽

Loss To Follow Up ◽

Mediation Analyses ◽

Reactive Protein ◽

Markers Of Inflammation

AbstractThis retrospective cohort study examined the roles of inflammation in acute kidney injury (AKI). Serum albumin and C-reactive protein (CRP) were used as markers of inflammation. Adults who underwent non–cardiac surgery from 2007 to 2011 were included. Exclusion criteria were urological surgery, obstetric surgery, missing data, and pre-operative dialysis. Subjects were followed until the end of 2015 or loss to follow-up. Associations between pre–operative albumin or CRP and post-operative AKI or association between AKI and mortality were examined by logistic or Cox regression, respectively. Mediation analyses were performed using albumin and CRP as mediators. Among 4,538 subjects, 272 developed AKI. Pre-operative albumin was independently associated with AKI (odds ratio [95% confidence interval (CI)]: 0.63 [0.48–0.83]). During a median follow-up of 4.5 years, 649 died. AKI was significantly associated with mortality (hazard ratio [HR] [95% CI]: 1.58 [1.22–2.04]). Further adjustment for pre-operative albumin and CRP attenuated the association (HR [95% CI]: 1.28 [0.99–1.67]). The proportions explained by mediating effects of lnCRP and albumin were 29.3% and 39.2% and mediation effects were statistically significant. In conclusion, inflammation is a predictor of AKI and a mediator of mortality after AKI. Interventions targeting inflammation might improve outcomes of AKI.

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Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Pathogens ◽

10.3390/pathogens9080615 ◽

2020 ◽

Vol 9 (8) ◽

pp. 615

Author(s):

Paula Mantula ◽

Johanna Tietäväinen ◽

Jan Clement ◽

Onni Niemelä ◽

Ilkka Pörsti ◽

...

Keyword(s):

Acute Kidney Injury ◽

Acute Phase ◽

Kidney Injury ◽

University Hospital ◽

Hantavirus Infection ◽

Puumala Virus ◽

Disappearance Rate ◽

Time Points ◽

Albumin Excretion ◽

Fever Onset

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon.

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HIGH-SENSITIVITY C-REACTIVE PROTEIN AND ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(20)30790-7 ◽

2020 ◽

Vol 75 (11) ◽

pp. 163

Author(s):

Giancarlo Silvio Marenzi ◽

Jeness Campodonico ◽

Nicola Cosentino ◽

Claudia Lucci ◽

Valentina Milazzo ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Acute Kidney Injury ◽

Kidney Injury ◽

High Sensitivity ◽

C Reactive Protein ◽

Reactive Protein

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The Association between Platelet Count and Acute Phase Response in Chronic Spontaneous Urticaria

BioMed Research International ◽

10.1155/2014/650913 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Alicja Kasperska-Zając ◽

Alicja Grzanka ◽

Jerzy Jarzab ◽

Maciej Misiołek ◽

Magdalena Wyszyńska-Chłap ◽

...

Keyword(s):

Platelet Count ◽

Acute Phase ◽

Acute Phase Response ◽

Healthy Subjects ◽

Phase Response ◽

Chronic Spontaneous Urticaria ◽

Distribution Width ◽

Reactive Protein ◽

Serum Crp

Background. The platelet parameters and C-reactive protein (CRP) are markers reflecting a systemic inflammatory response. Among those, CRP is one of the major proteins helpful in determination of severity/activity of chronic spontaneous urticaria (CSU).Aim. To determine relationships between platelet activation indices and serum concentration of CRP, the best marker of acute phase response, and their potential clinical use in CSU patients.Methods. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet count as well as serum CRP concentration were measured in CSU patients, showing different degrees of urticarial severity, and in the healthy subjects.Results. No significant differences were found in MPV and PDW between CSU group and the healthy subjects. The platelet count was significantly higher in moderate-severe CSU than that of the controls and mild CSU patients. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects and significantly correlated with the platelet count in CSU patients.Conclusions. Acute phase response in CSU is associated with the increased number of circulating platelets in patients with more severe symptoms. It seems that simple determination of platelet size indices is not a reliable indicator of CSU severity/activity.

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Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease.

Clinical Chemistry ◽

10.1093/clinchem/35.5.869 ◽

1989 ◽

Vol 35 (5) ◽

pp. 869-871 ◽

Cited By ~ 12

Author(s):

J Paavonen ◽

M Lehtinen ◽

M Lehto ◽

S Laine ◽

R Aine ◽

...

Keyword(s):

Pelvic Inflammatory Disease ◽

Acute Phase ◽

Trypsin Inhibitor ◽

Inflammatory Disease ◽

Acute Phase Proteins ◽

Endometrial Biopsy ◽

C Reactive Protein ◽

Reactive Protein ◽

Acute Pelvic Inflammatory Disease ◽

Severe Infections

Abstract We measured tumor-associated trypsin inhibitor (TATI) and C-reactive protein (CRP) in serum of 29 patients with proven pelvic inflammatory disease (PID). TATI values were increased in seven (24%), paralleling increases in CRP. TATI was increased by about 3.5-fold in seven of eight patients with CRP concentrations greater than 90 mg/L, but in none of 21 patients with CRP concentrations less than 90 mg/L. TATI concentration and severity of PID as determined by laparoscopy or endometrial biopsy were not correlated. These results suggest that, in severe infections, regulation of TATI synthesis resembles that of acute-phase proteins.

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