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Clinical Journal of the American... Dec 2015Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute... (Review)
Review
Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.
Topics: Acute Kidney Injury; Adaptive Immunity; Animals; Anti-Inflammatory Agents; Autoimmunity; Cytokines; Genetic Therapy; Glomerulonephritis; Humans; Immunity, Innate; Immunologic Factors; Molecular Targeted Therapy; Signal Transduction
PubMed: 25941193
DOI: 10.2215/CJN.07590714 -
The American Journal of Tropical... Dec 2018Acute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease following infection with nephritogenic strains of Group A . In 1991, APSGN became... (Comparative Study)
Comparative Study Review
Acute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease following infection with nephritogenic strains of Group A . In 1991, APSGN became notifiable in the Northern Territory (NT) of Australia with cases recorded on the NT Notifiable Disease Database (NTNDS). The case definition of a confirmed case requires laboratory definitive evidence or laboratory suggestive evidence in conjunction with a clinically compatible illness. Probable cases require clinical evidence only. Acute post-streptococcal glomerulonephritis notifications from 2009 to 2016 were extracted from the NTNDS. Of the 322 cases, 261 were confirmed and 61 probable. The majority, 304 (94%), were Aboriginal and the median age was 8 years (range: 0-62 years). Incidence for confirmed cases was 13.8/100,000 person-years, with inclusion of probable cases increasing incidence to 17.0/100,000 person-years. Highest incidence of confirmed cases was in Aboriginal children less than 15 years of age at 124.0 cases/100,000 person-years. The rate ratio of confirmed cases in Aboriginal to non-Aboriginal Australians was 18.9 (95% confidence interval: 11.4-33.6). Recent trends show a consistently high number of notifications annually with less frequent outbreaks. The Aboriginal population of the NT continues to have high rates of APSGN with recent trends showing higher rates than previously reported. Sustained preventative efforts and continued surveillance strategies are needed.
Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Disease Notification; Disease Outbreaks; Female; Glomerulonephritis; Humans; Infant; Infant, Newborn; Kidney; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; Northern Territory; Streptococcal Infections; Streptococcus pyogenes; White People
PubMed: 30398135
DOI: 10.4269/ajtmh.18-0093 -
Infection and Immunity Dec 1982We examined the hypothesis that streptococcal neuraminidase may alter host serum immunoglobulin G so that autoantibodies are formed which lead to immune complexes and...
We examined the hypothesis that streptococcal neuraminidase may alter host serum immunoglobulin G so that autoantibodies are formed which lead to immune complexes and acute glomerulonephritis. We confirmed the observation that T-type 4 and T-type 12 streptococci (both associated with acute glomerulonephritis) are the most likely of many types studied to produce neuraminidase. However, we did not find this enzyme to be produced by any of 23 streptococcal strains isolated from patients with nephritis, whereas it was produced by two strains from patients with rheumatic fever and by one strain from a patient with scarlet fever. Also, we were unable to find direct or indirect evidence of increased neuraminidase activity in the sera of six patients with acute glomerulonephritis when they were compared with the sera of six patients with acute rheumatic fever and with those of six normal subjects.
Topics: Acute Disease; Glomerulonephritis; Humans; Neuraminidase; Sialic Acids; Streptococcal Infections; Streptococcus
PubMed: 7152666
DOI: 10.1128/iai.38.3.1196-1202.1982 -
American Journal of Kidney Diseases :... May 2023The monotypic variant of immunotactoid glomerulopathy (ITG), strongly associated with low-grade lymphoproliferative disorders, is characterized histologically by...
The monotypic variant of immunotactoid glomerulopathy (ITG), strongly associated with low-grade lymphoproliferative disorders, is characterized histologically by glomerulonephritis and microtubular deposits of monoclonal immunoglobulin G (IgG). We report a patient with high-risk κ light chain multiple myeloma who presented with acute kidney injury, hematuria, proteinuria, and hypocomplementemia. Kidney biopsy revealed immunotactoid glomerulopathy concomitant with κ light chain myeloma cast nephropathy. The glomerular microtubular deposits stained for κ light chain and C3 only. Proteomic analysis of glomeruli and atypical casts detected κ light chain constant domain and a single VL variability subgroup (IGKV3) in both glomeruli and casts (without γ, α, or μ heavy chain or λ light chain). C3, C5, C6, C7, and C9 were detected in glomeruli. No autoantibodies against alternative pathway of complement proteins were detected. Despite clone-directed chemotherapy, the patient remained on dialysis treatment. For this light chain-only variant of immunotactoid glomerulopathy, pathogenesis potentially involves activation of the alternative pathway of complement by a nephrotoxic κ light chain.
Topics: Humans; Proteomics; Glomerulonephritis; Kidney Glomerulus; Kidney Diseases; Proteinuria
PubMed: 36328099
DOI: 10.1053/j.ajkd.2022.08.025 -
Australian Family Physician Nov 2005Glomerulonephritis (GN) is an important cause of both acute and chronic kidney disease, however the diagnosis can be difficult due to the variability of presenting... (Review)
Review
BACKGROUND
Glomerulonephritis (GN) is an important cause of both acute and chronic kidney disease, however the diagnosis can be difficult due to the variability of presenting features.
OBJECTIVE
This article aims to develop a structured approach to the investigation of patients with markers of kidney disease, and promote the recognition of patients who need further assessment. Consideration is given to the importance of general measures required in the care of patients with GN.
DISCUSSION
Glomerulonephritis is not an everyday presentation, however recognition and appropriate management is important to prevent loss of kidney function. Disease specific treatment of GN may require specialist care, however much of the management involves treatment of the associated complications such as oedema, achievement of target blood pressure and proteinuria reduction, and prevention and treatment of associated complications.
Topics: Adult; Anti-Glomerular Basement Membrane Disease; Antibodies, Antineutrophil Cytoplasmic; Child; Family Practice; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Lupus Erythematosus, Systemic; Nephrotic Syndrome; Physician's Role; Practice Guidelines as Topic; Streptococcal Infections; Vasculitis
PubMed: 16299623
DOI: No ID Found -
Clinical Journal of the American... Sep 2017By definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in... (Review)
Review
By definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viral-associated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%-20% of HBV patients may be coinfected with hepatitis C and 5%-10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein-Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention.
Topics: Animals; Antiviral Agents; Glomerulonephritis; Hepatitis B; Hepatitis B virus; Host-Pathogen Interactions; Humans; Kidney Glomerulus; Prevalence; Prognosis; Risk Factors; Virus Replication
PubMed: 27797900
DOI: 10.2215/CJN.09180816 -
Hawai'i Journal of Health & Social... May 2020Acute post-streptococcal glomerulonephritis (APSGN) is a disorder of inflammation in the glomeruli and vasculature of the kidneys that is caused by immune-complex...
Acute post-streptococcal glomerulonephritis (APSGN) is a disorder of inflammation in the glomeruli and vasculature of the kidneys that is caused by immune-complex formation after Streptococcus pyogenes infection. Most patients with APSGN present with macroscopic hematuria, edema, and hypertension, however presentation can vary from no symptoms to severe proteinuria, or even acute renal failure. This study sought to estimate the incidence of APSGN among children in Hawai'i, to identify populations at increased risk for APSGN, and to recognize risk factors correlated with the length of hospitalization by subtype of APSGN (eg, pyoderma-associated, pharyngitis-associated). This retrospective review of 106 patients found that the incidence of APSGN in Hawai'i is greater than 4 per 100,000 children, which is significantly higher than the incidence of APSGN in high-income countries at 0.3 per 100,000 children. This increased incidence may be due to Hawai'i's unique racial group composition and therefore the unique immunologic response of the children of Hawai'i (particularly Pacific Islanders, who represent 62% of patients with APSGN in this study, but only represent 10% of Hawai'i's general population). In addition, there may be increased prevalence of nephritogenic strains of Streptococcus pyogenes in Hawai'i. The length of hospitalization was significantly increased in children with elevated serum creatinine levels (P <.0001) and lower bicarbonate levels (P =.0003).
Topics: Child; Child, Preschool; Female; Glomerulonephritis; Hawaii; Hospitalization; Humans; Incidence; Length of Stay; Male; Streptococcal Infections; Streptococcus pyogenes
PubMed: 32432220
DOI: No ID Found -
Postgraduate Medical Journal Jan 1983A patient with seven attacks of acute glomerulonephritis is described. Following each attack renal function returned to normal. Investigations strongly suggested immune...
A patient with seven attacks of acute glomerulonephritis is described. Following each attack renal function returned to normal. Investigations strongly suggested immune complex disease as the cause of the nephritis but extensive tests failed to define the antigen. The possibility of an exogenous self-administered antigen is considered.
Topics: Adult; Female; Glomerulonephritis; Humans; Immune Complex Diseases; Recurrence
PubMed: 6223290
DOI: 10.1136/pgmj.59.687.60 -
Journal of Nephrology Apr 2016Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly... (Review)
Review
Onconephrology is an emerging medical subspecialty focused on the numerous interconnections between cancer and kidney diseases. Patient with malignancies commonly experience kidney problems including acute kidney injury, tumor lysis syndrome, fluid and electrolyte disorders and chronic kidney disease, often as a consequence of the anti-cancer treatment. Conversely, a number of glomerulopathies, tubulopathies and vascular renal diseases can early signal the presence of an underlying cancer. Furthermore, the administration of immunosuppressive drugs, especially cytotoxic drugs and calcineurin inhibitors, may strongly impair the immune response increasing the risk of cancer. The objective of this review article is to: (i) discuss paraneoplastic glomerular disease, (ii) review cancer as an adverse effect of immunosuppressive agents used to treat glomerulopathies, and (iii) in the absence of international approved guidelines, propose a screening program based on expert opinion aimed at guiding nephrologists to early detect malignancies during their clinical practice.
Topics: Antineoplastic Agents; Glomerulonephritis; Humans; Immunocompromised Host; Immunosuppressive Agents; Medical Oncology; Neoplasms; Nephrology; Paraneoplastic Syndromes; Risk Assessment; Risk Factors
PubMed: 26498294
DOI: 10.1007/s40620-015-0234-9 -
The American Journal of Tropical... Oct 2011Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was... (Comparative Study)
Comparative Study Review
Data relating to acute post-streptococcal glomerulonephritis (APSGN) from the notifiable diseases surveillance system in the Northern Territory of Australia was extracted and analyzed. Isolates of Streptococcus pyogenes from confirmed cases were emm sequence typed. From 1991 to July 2008, there were 415 confirmed cases and 23 probable cases of APSGN notified. Four hundred fifteen (94.7%) of these were Indigenous Australians and 428 (97.7%) were people living in remote or very remote locations. The median age of cases was 7 years (range 0-54). The incidence of confirmed cases was 12.5/100,000 person-years, with an incidence in Indigenous Australian children younger than 15 years of age of 94.3 cases/100,000 person-years. The overall rate ratio of confirmed cases in Indigenous Australians to non-Indigenous Australians was 53.6 (95% confidence interval 32.6-94.8). Outbreaks of disease across multiple communities occurred in 1995 (N = 68), 2000 (N = 55), and 2005 (N = 87 [confirmed cases]). Various emm types of S. pyogenes were isolated from cases of APSGN including some types not previously recognized to be nephritogenic. The widespread outbreak in 2005 was caused by emm55.0 S. pyogenes. Acute post-streptococcal glomerulonephritis continues to occur in remote Indigenous communities in Australia at rates comparable to or higher than those estimated in developing countries. Improvements in preventative and outbreak control strategies are needed.
Topics: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Disease Outbreaks; Glomerulonephritis; Humans; Incidence; Infant; Infant, Newborn; Middle Aged; Northern Territory; Streptococcal Infections; Streptococcus pyogenes; Young Adult
PubMed: 21976576
DOI: 10.4269/ajtmh.2011.11-0185