The complement system (CS) has recently been recognized as a bridge between innate and adaptive immunity that constitutes a very complex mechanism controlling the clearance of pathogens, cellular ...debris, and immune complexes. Out of three known pathways of complement activation, the alternative pathway (AP) plays a critical role in host defense by amplifying the complement response, independently of initiation pathway and continuously maintaining low-level activity in a process called ‘thick-over.’ A key molecule of the CS is C3, in which the AP is constantly activated. To prevent host cell destruction, a group of the AP regulators tightly controls this pathway of the CS activation. Acquired and genetic abnormalities of the CS may alter the delicate balance between enhancing and inhibiting the AP cascade. These can lead to the uncontrolled CS activation, inflammatory response, and subsequent tissue damage. Since complement components are locally produced and activated in the kidney, the abnormalities targeting the AP may cause glomerular injury. C3 glomerulopathy is a new entity, in which the AP dysregulation has been well established. However, recent studies indicate that the AP may also contribute to a wide range of kidney pathologies, including immune-complex-mediated glomerulonephritis (GN), pauci-immune GN, and primary membranous nephropathy (PMN). This article provides insight into current knowledge on the role of the AP in the pathogenesis of glomerular diseases, focusing mainly on various types of primary and secondary GN and PMN.
Despite the progress made in treating bipolar and unipolar affective disorders, lithium carbonate is still a common drug in psychiatric practice. Lithium‐related renal side effects include ...nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy, and acute kidney injury (AKI). Nephrotic syndrome (NS) is an uncommon but severe complication of lithium treatment. We present a 49‐year‐old female treated with lithium carbonate due to a recurrent depressive disorder who developed NS during this therapy. NS spontaneously remitted after the drug withdrawal. Since her lithium serum levels were within the recommended values, we performed a retrospective analysis of lithium‐induced NS cases trying to determine causes predisposing to the NS development, underlying histopathology, and preservation or irreversible loss of kidney function. This analysis revealed that in lithium‐induced NS with AKI, lithium serum level was the key determinant of AKI development (the β coefficient = 0.8499 with a confidence interval ranging from 0.7452 to 0.9546 and p value < 0.0001). In these cases, the underlying pathology was mainly minimal change disease (MCD), which was quickly reversible upon the drug withdrawal. The development of chronic kidney disease (CKD) seemed to be associated with lithium therapy duration. However, the multiple regression analysis for CKD as the dependent variable showed that the decisive factor was focal segmental glomerulosclerosis (FSGS) as the underlying pathology (the β coefficient = 0.7866 with a confidence interval ranging from 0.600 to 0.9704 and the p value < 0.0001). Thus, we conclude that in lithium‐induced NS/AKI, serum lithium levels contribute to these complications, while FSGS lesions are responsible for CKD's disease progression.
We present a new lithium‐induced nephrotic syndrome (NS) case with a retrospective analysis of lithium‐induced NS cases trying to determine causes triggering NS development, underlying histopathology, preservation, or irreversible loss of kidney function. We show that in lithium‐induced NS with acute kidney injury, serum lithium levels contribute to these complications, while focal segmental glomerulosclerosis lesions are responsible for chronic kidney disease progression.
Polypharmacy is a challenging issue in geriatrics. The aim of the study was to characterize correlates of polypharmacy in the PolSenior project. The PolSenior project, was a comprehensive survey in a ...large and longitudinal representative sample of thePolish older population. The project was conducted by the International Institute of Molecular and Cell Biology in Warsaw between 2008 and 2011. All medications consumed during the week preceding the survey were evaluated for each participant (n = 4793, including 2314 females (48.3%)). Thereafter, the percentage of those with polypharmacy (at least 5 medications) and excessive polypharmacy (at least 10 medications) was calculated, and their correlates were determined. The average number of medications used by participants was 5.1 ± 3.6, and was higher in females than in males (5.5 ± 3.5 vs. 4.8 ± 3.5;
< 0.001). Polypharmacy characterized 2650 participants (55.3%) and excessive polypharmacy-532 of them (11.1%). The independent correlates associated withpolypharmacy were: age over 70 years, female sex, higher than primary education, living in an urban area, comorbidities, any hospitalization during past five years, and visiting general practicioners at least yearly. As for correlates with excessive polypharmacy, they were: age 80-84 years, female sex, living in an urban area, diagnosis of at least four chronic diseases, and at least two hospitalizations in the last five years. This study serves as a starting place to understand patient characteristics associated with polypharmacy, excessive polypharmacy, and identify targeted interventions.
Purpose
Neutropenia, defined as a number of neutrophils in patients’ blood specimen lower than 1500 cells/μm
3
, is a common adverse event during myelosuppressive oncological chemotherapy, ...predisposing to febrile neutropenia (FN). Patients with coexisting moderate-to-severe chronic kidney disease (CKD) have an increased risk of FN, included in the guidelines for the primary prophylaxis of FN. However, this does not include mild kidney function impairment with estimated glomerular filtration rate (eGFR) 60–89 ml/min/1.73 m
2
. This prospective study analyzed the risk of neutropenia in patients on chemotherapy without indication for the primary prophylaxis of FN.
Methods
The study enrolled 38 patients starting chemotherapy, including 26 (68.4%) patients aged 65 years or more. The median duration of follow-up was 76 days. The methodology of creatinine assessment enabled the use of the recommended CKD-EPI formula for identifying patients with a mild reduction of glomerular filtration.
Results
Sixteen (42.1%) patients developed at least G2 neutropenia without episodes of FN. Only five (13.1%) patients had eGFR < 60 ml/min/1.73 m
2
, while 15 (62.5%) eGFR < 90 ml/min/1.73 m
2
. The relative risk of neutropenia in patients with impaired eGFR was over six times higher than in patients with eGFR > 90 ml/min/1.73 m
2
(RR = 6.08; 95%CI:1.45–27.29;
p
< 0.01).
Conclusions
Our observation indicates that even a mild reduction in eGFR is a risk factor for the development of neutropenia and a potential risk factor for FN.
Multiple drugs used in palliative care, including most opioids or their active metabolites may accumulate in patients with abnormal renal function, leading to serious adverse effects. The incidence ...and severity of renal impairment in palliative care inpatients has not been evaluated. The aim of the study was to investigate the incidence and severity of renal impairment in palliative care inpatients.
A retrospective analysis of medical records of patients admitted to the palliative care ward was performed. Estimated glomerular filtration rate (eGFR) was derived using the Cockcroft-Gault (C-G) and abbreviated Modification of Diet in Renal Disease (aMDRD) equations.
Serum creatinine levels (SCr) were determined in 332 subjects aged 66.4±11.80 years (194 women; mean body mass index BMI 22.7±5.21 kg/m(2)). Mean SCr was 107.7±112.31 μmol/L. Elevated SCr (>115 μmol/L) was found in 20.2% of patients. Mean eGFR calculated with C-G and aMDRD equations was 66.6±38.52 mL/min and 78.7±43.55 mL/min/1.73 m(2), respectively. Between 35.2% and 51.8% of patients had eGFR <60 mL/min/1.73 m(2) (depending on the equation used). More than 10% of patients had eGFR <30 mL/min/1.73 m(2). In patients with normal SCr, between 18.9% and 39.2% had eGFR <60 mL/min/1.73 m(2).
Renal impairment is common in palliative care inpatients, including considerable number of subjects with moderately to severely reduced kidney function.
Abstract Ficolin-3 (also called H-ficolin or Hakata antigen) is the most potent activator of the lectin pathway of complement in vitro . Its genetically determined deficiency in Caucasians is ...associated with a frame-shift mutation +1637delC (rs28357092) of the FCN3 gene. When it was described for the first time, it was postulated to be strictly associated with enhanced susceptibility to infections. At present, with our knowledge extended by several other patients that issue seems to be more complicated and less clear-cut. Two new cases of primary Ficolin-3 deficiency are reported here: a 50-year old male, suffering from membranous nephropathy and an 11-month old male infant who was operated on to repair congenital heart disease. Based on those cases and a literature review, we conclude that the clinical consequences of congenital Ficolin-3 deficiency are still unclear and such questions as whether it may be life-threatening or acts as a disease modifier remain to be elucidated.
A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression ...of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA
in situhybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1β mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1β in the lamina propria compartment.
The results of recent studies suggest that there is a link between the presence of antibodies against C1q (anti-C1q Abs) and kidney involvement in systemic lupus erythematosus (SLE). However, it ...remains unclear whether the clinical symptoms of lupus nephritis (LN) may be associated with the presence of anti-C1q Abs in serum.
The aim of the study was to compare the prevalence and levels of anti-C1q Abs and antibodies against double-stranded DNA (anti-dsDNA Abs), circulating immune complexes binding C1q (CIC-C1q), as well as complement components C3 and C4 in the sera of patients with LN in relation to the clinical activity of SLE and symptoms of LN.
The study involved 48 patients with LN and 66 healthy controls. Anti-dsDNA Abs, anti-C1q Abs, and CIC-C1q levels were determined by immunoenzymatic methods, while C3 and C4 by immunoturbidimetry. SLE activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).
Anti-dsDNA Abs, anti-C1q Abs, and CIC-C1q were detected in 77%, 60%, and 43.7% of the patients with LN, respectively. The prevalence and mean levels of anti-dsDNA and anti-C1q Abs were significantly higher in patients with active LN than in those with inactive LN or controls. The levels of C3 and C4 were significantly lower in active LN than in inactive LN or controls. In active LN, a positive correlation between anti-C1q and anti-dsDNA Abs was observed. In patients with detected anti-C1q Abs, microhematuria (59% vs. 16%, P = 0.003), urinary casts (28% vs. 8%, P = 0.02), and low levels of serum C3 (P = 0.03) and C4 (P = 0.01) were observed statistically significantly more often.
Simultaneous presence of hematuria and anti-C1q Abs may indicate an ongoing inflammatory process in the glomeruli in patients with SLE.
Celem pracy jest przedstawienie przypadku nietypowego zatrucia węglanem litu u 57-letniej kobiety z chorobą afektywną dwubiegunową leczonej węglanem litu przez około 30 lat. Chora została przyjęta do ...szpitala z powodu znacznego pobudzenia. W wywiadzie uzyskanym od rodziny uwagę zwracała znaczna utrata masy ciała w ciągu ostatniego roku. W szpitalu pacjentce podano haloperidol i klonazepam. Badania laboratoryjne ujawniły bardzo wysokie stężenie litu – 3.79 mmol/l N: 0,6-1,2 mmol/l oraz podwyższone stężenie kreatyniny (3.6 mg/dl) i mocznika (110 mg/dl) w surowicy krwi. Pacjentka została przekazana do oddziału toksykologicznego, gdzie wykonano hemodializę z przyczyn toksykologicznych i wdrożono intensywne leczenie. Mimo szybkiego obniżenia stężenie litu stan chorej stopniowo ulegał pogorszeniu. Chora zmarła w piątym dniu hospitalizacji. Badania pośmiertne ujawniły zmiany wielotorbielowate nerek. Opracowując opinię sądowo-lekarską dotyczącą prawidłowości postępowania medycznego przyjęto, iż przyczyną zgonu było zatrucie litem w przebiegu zaawansowanej przewlekłej choroby nerek na podłożu ich torbielowatości, stanowiącej prawdopodobnie powikłanie wieloletniego stosowania preparatów litu. Analiza dokumentacji lekarskiej ujawniła, że chora odmawiała od 18 lat zalecanego przez psychiatrę monitorowania stężenia litu. Przypadek ten pokazuje, że zarówno psychiatrzy jak i toksykolodzy powinni mieć świadomość możliwego zatrucia węglanem litu związanego z pogorszeniem czynności wydalniczej nerek. Dlatego ocena funkcji nerek powinna być nieodłącznym elementem monitorowania terapii litem.
The study aims to present a case of atypical poisoning with lithium carbonate in a 57-year-old woman treated for bipolar affective disorder with lithium carbonate for about 30 years. The patient was admitted to the hospital with significant agitation. An important finding obtained from the family interview was the patient's significant weight loss over the past year. In the hospital, the patient received haloperidol and clonazepam. Laboratory tests showed a very high blood lithium concentration of 3.79 mmol/l N: 0.6─1.2 mmol/l and elevated serum concentrations of creatinine (3.6 mg/dl) and urea (110 mg/dl). The patient was transferred to the toxicology department, where hemodialysis was performed and intensive treatment initiated. Despite the rapid decrease in lithium levels, her condition gradually deteriorated. The patient died on the fifth day of hospitalization. The autopsy revealed polycystic kidney disease (PKD). During the preparation of the medico-legal report on the correctness of the medical treatment, it was assumed that the cause of death was lithium carbonate poisoning in the course of advanced chronic kidney disease due to PKD, probably a consequence of long-term lithium therapy. The analysis of medical records revealed that despite her psychiatrist's recommendation, the patient had been refusing the monitoring of lithium levels for the past 18 years. This case demonstrates that both psychiatrists and toxicologists should be aware of possible lithium poisoning upon the deterioration of renal function. Therefore, assessment of renal function should be an integral part of monitoring lithium therapy.
Background: Interleukin-8 (IL-8) is considered a deleterious chemokine involved in renal injury in glomerulonephritis (GN). IL-8 may be released as a 77-amino acid (AA) peptide or 72-AA protein. ...Methods: We evaluated gene and protein expression of IL-8 in 53 renal biopsy specimens from patients with GN and 9 control kidneys. Nonradioactive in situ hybridization and reverse-transcriptase polymerase chain reaction (RT-PCR) were applied to detect IL-8 messenger RNA (mRNA). In immunohistochemistry, a double-staining technique with the use of antibodies against the 77-AA and 72-AA forms of IL-8, as well as glomerular cell antigens, was used. Results: By in situ hybridization, IL-8 mRNA was detected in normal glomerular, tubular, and some interstitial cells. The RT-PCR study showed that IL-8 mRNA expression in control kidneys significantly exceeds that in specimens with GN (0.89 ± 0.82 versus 0.21 ± 0.20; P < 0.003). In control kidneys, major sources of 77-AA IL-8 were podocytes and endothelial cells of interstitial vessels, whereas tubular epithelial cells expressed minute amounts of 72-AA IL-8. In GN specimens, podocyte expression of 72-AA IL-8 varied notably, with the greatest level found in minimal change disease and the lowest level found in acute endocapillary GN. Conversely, increased glomerular expression of the 72-AA form of IL-8 was a general feature of GN, with its level significantly exceeding that of the 77-AA form in acute endocapillary GN (P < 0.01). Conclusion: Our results suggest that intrinsic glomerular cell production of IL-8, in particular the 77-AA form, may be relevant for preservation of the glomerular architecture.
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