GlomerulonephritisN00.9

The first person to describe proteinuria as an expression of chronic kidney disease and to describe chronic kidney disease was Richard Bright, who first wrote about it in detail in 1831. He also pointed out the frequent occurrence of glomerulonephritis in the context of alcoholism (Singer 1999).

Sir William Osler, in his textbook of internal medicine in 1899, first described glomerulonephritis as an "Acute diffuse nephritis due to the action of cold or toxic substances on the kidneys" (Haller 2003).

Glomerulonephritis (GN) refers to a series of immune-mediated diseases with intraglomerular inflammation and cellular proliferation (Herold 2022).

Classification

One differentiates between

- 1. primary GN

These include diseases that primarily occur in the glomeruli. Evidence of systemic disease is absent (Herold 2022). Examples include:

- IgA- glomerulonephritis

- membranous glomerulonephritis (MGN)

- C3- glomerulopathy

- minimal change glomerulonephritis

- membranoproliferative glomerulonephritis

- postinfectious glomerulonephritis

- focal segmented glomerulonephritis (Stahl 2016).

- 2. secondary GN

In this case, there is primarily a systemic disease such as collagenosis, endocarditis lenta, vasculitis, to which renal involvement is associated (Herold 2022). Examples include:

- systemic lupus erythematosus with nephritis

- ANCA-associated glomerulonephritis

- Anti- GBM nephritis

- Schönlein- Henoch- Purpura (Stahl 2016).

The classification of primary and secondary GN is pathologically possible only by including serological markers, histology, and clinical symptoms (Herold 2022).

Furthermore, depending on the severity of the immune process, one differentiates between an

- an acute form of progression (Kasper 2015)

- subacute form of progression (Anders 2023)

- chronic form of progression (Kasper 2015)

Anders et al (2023) suggest for optimal therapy to divide the classification of GN according to their immunopathogenesis into the following 5 categories:

- infection-related GN

- autoimmune GN

- alloimmune GN

- autoinflammatory GN

- monoclonal gammopathy-related GN (Anders 2023)

GN is a relatively rare kidney disease. The most common among GN is primary glomerulonephritis with 65.3%, which presents as immunoglobulin A nephropathy in 23.9%. Secondary GN was found in 24.6%, with lupus nephritis being the most common at 41.8% (AlYousef 2020).

GN is responsible for chronic kidney disease in 18.7% in Germany and end-stage renal disease in 30-36% of children and adolescents in the United States (Anders 2023).

The prevalence of autoimmune GN is unclear to date (Anders 2023)

It is now thought that environmental influences, particularly infectious processes, trigger host responses in genetically susceptible individuals that then lead to GN (Couser 2016).

- Asymptomatic GN:

The causes can be Alport syndrome, IgA nephropathy (so-called Berger's disease), overflow proteinuria in multiple myeloma, thin basement membrane syndrome, functional proteinuria in the context of exercise, fever or in heart failure or as orthostatic protein uria of < 1 g / d in children or young adults. Typically, no proteinuria is found in morning urine in the orthostatic form (Herold 2022).

- Rapid- progressive GN (also referred to as sickle-shaped GN):

Causes may be idiopathic or represent the renal manifestation of vasculitis (Herold 2022)

- Macro- or microhematuria:

These may be caused by intercurrent infections or by IgA nephropathy (Herold 2022)

- Nephritic syndrome:

May be caused by acute postinfectious GN (Herold 2022).

- Nephrotic syndrome:

GN with nephrotic syndrome may be caused by, for example, minimal- change glomerulopathy, membranoproliferative GN, membranous GN, cryoglobulinemic MPGN, focal segmental glomerulosclerosis, dense- deposit disease, multiple myeloma, diabetic nephropathy, renal vein thrombosis, amyloidosis (Herold 2022).

Both humoral and cell-mediated immune mechanisms play a role in GN:

- Anti- GBM antibody mediated GN.

In this case, linear deposits of IgG against the Goodpasture antigen are found. Normally, this antigen is a normal cellular component of the non-collagenous domain of type IV collagen (Herold 2022).

- Immune complex mediated GN

In this case, immune complexes are distributed throughout the glomerular capillary wall as is the case, for example, in postinfectious GN and lupus nephritis (Herold 2022).

- ANCA-associated GN

Anti-neutrophil cytoplasmic antibody-associated GN induces glomerular injury by interacting with components of neutrophil granules (Herold 2022).

- Activation of cell-mediated immune processes.

This can also lead to glomerular injury. This process is found in proliferative and non-proliferative glomerulopathies, for example (Herold 2022).

The clinical picture can be very different in GN. It can occur:

- arterial hypertension

- hematuria (Anders 2023)

- edema / anasarca

- foamy urine (due to proteinuria)

(Kasper 2015)

- Asymptomatic GN:

The disease is almost always detected incidentally on the basis of urine findings (Herold 2022).

- Rapid- progressive GN (also referred to as sickle-shaped GN):

- Reduced performance

- fatigue

- Inappetence

- arthralgias

- myalgias

- petechiae

- edemas

- arterial hypertension (Frank 2021)

- Chronic GN:

Subjectively, only minor complaints are found at most. Arterial hypertension is almost always present (Herold 2022).

Appropriate basic diagnostics should be performed on an outpatient basis in the practice. The best method for further classification of GN and appropriate therapy or assessment of the diagnosis is renal biopsy (Herold 2022). In addition, genetic testing such as panel- sequencing for cytokine, interferon and complement pathways (autoinflammation), Sanger- sequencing for collagens, apolipoprotein L1 (APOL1) risk alleles (glomerulosclerosis), whole exome sequencing (primary immunodeficiencies) may be required (Anders 2023).

- Chronic GN:

Sonographically, the kidneys usually present reduced in size. Biopsy is usually no longer indicated at this stage, as it would have no therapeutic consequences (Herold 2022).

Typical for a GN are dysmorphic erythrocytes and erythrocyte cylinders. Persistent non-selective proteinuria between 1 - 2 g / 24 d is common in GN (Kasper 2015).

- Asymptomatic GN:

In this case - since there are no symptoms - microhematuria is often found as an incidental finding. The glomerular filtration rate is normal in these cases and there is no evidence of renal involvement in the presence of systemic disease.

In addition, proteinuria of usually < 1.5 g/d may be present in some patients.

Arterial hypertension is not found in this case (Herold 2022).

- Rapid- progressive GN (also referred to as sickle-shaped GN):

- Rapid increase in serum creatinine (Kasper 2015).

- Determination of various antibodies

- Antistreptolysin titer

- cryptoglobulins (Frank 2021)

- Nephritic syndrome:

- Proteinuria between 1 - 2 g / 24 h

- Hematuria with erythrocyte inclusions

- pyuria

- Increase in serum creatinine

- hypercholesterolemia

- Hypoalbuminemia (Kasper 2015)

- Nephrotic syndrome:

- Proteinuria > 3 g / d

- Hypoproteinemia

- AT (III) decreased

- Hyperlipidemia (Müller 2023)

- Chronic GN:

- Erythrocyturia

- proteinuria

- possibly also signs of a nephrotic syndrome (Herold 2022)

- Non-inflammatory glomerulopathies such as diabetic glomerulosclerosis, eclampsia, amyloidosis (Herold 2022).

- Terminal renal failure

GN is the second most common cause of ESRD with 19% (Herold 2022)

- Chronic kidney disease

Chronic renal failure often develops from GN with increased risk of cardiovascular disease and progressive renal failure (Herold 2022).

- Infection-related GN:

Here, therapeutically, the location of infection control and its targeted therapy are primarily important (Anders 2023).

- Autoimmune GN:

Therapeutically, transient or sustained suppression of the adaptive immune response should occur (Anders 2023).

- Alloimmune GN:

In this case, sustained suppression of the adaptive immune response is required (Anders 2023).

- Autoinflammatory GN:

In this form of GN, inhibition of specific cytokines or complement factors must be used (Anders 2023).

- Monoclonal gammopathy-induced GN (Anders 2023).

This form of GN necessitates clone-directed therapy (Anders 2023).

- Rapid- progressive GN (also referred to as sickle-shaped GN):

Therapy is with immunosuppressants (Frank 2021).

Both morbidity and mortality are significant in GN (AlYousef 2020).

Rapid-progressive GN represents a nephrological emergency and, without targeted therapy, leads to rapid loss of renal function within days to weeks (Frank 2021).

1. AlYousef A, AlSahow A, AlHelal B, Alqallaf A, Abdallah E, Abdellatif M, Nawar H, Elmahalawy R (2020) Glomerulonephritis histopathological pattern change. BMC Nephrol. 21 (1) 186
2. Anders H J, Kitching A R, Leung N, Romagnani P (2023) Glomerulonephritis: immunopathogenesis and immunotherapy. Nature Reviews Immunology 23: 453 - 471
3. Couser W G (2016) Pathogenesis and treatment of glomerulonephritis-an update. J Bras Befrol. 38 (1) 107 - 122
4. Frank H, Hofmann W, German Society of Nephrology (DGfN); German Society for Clinical Chemistry and Laboratory Medicine (DGKL). (2021) Interdisciplinary S2k-guideline - Rational laboratory diagnostics for the evaluation of acute kidney injury and progressive kidney disease - long version.
5. Haller H, Gross W L (2003) Glomerulonephritis. Der Internist 44: 1073 - 1074
6. Herold G et al (2022) Internal medicine. Herold Publishers 605 - 606
7. Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 1831 - 1836.
8. Müller M (2023) Laboratory medicine: microbiology, clinical chemistry, infectiology, transfusion medicine in question and answer. IRM books, BoD (Books on Demand) 124, 389.
9. Singer M V, Teyssen S (1999) Alcohol and alcohol sequelae: basic principles - diagnosis - therapy. Springer Verlag Berlin / Heidelberg / New York 383
10. Stahl R, Hoxha E (2016) Glomerulonephritis. Dtsch Med Wochenschr. 141: 960 - 968.