Complement factor H-related protein 5 (CFHR5) nephropathy is a form of inherited kidney disease which is endemic in Cyprus and is caused by a mutation in the gene
CFHR5
Complement factor H-related protein 5 is a protein that in humans is encoded by the ''CFHR5'' gene.
Function
CFHR5 is structurally related to complement factor H which plays an important role in the regulation of a branch of the innate immune sys ...
.
It is thought to affect up to 1:6000 Cypriots but has not been reported in anybody who is not of Cypriot descent.
Presentation
Sometimes the disease is associated with visible blood in the urine, usually at the time of respiratory or other infections and this is thought to result from stimulation of the immune system leading to damage in the kidneys.
Diagnosis
The diagnosis can be confirmed on a blood sample using a
genetic test
Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or ...
.
CFHR5 nephropathy usually presents with microscopic amounts of blood in the urine, detectable on a routine
urine dipstick
A urine test strip or dipstick is a basic diagnostic tool used to determine pathological changes in a patient's urine in standard urinalysis.
A standard urine test strip may comprise up to 10 different chemical pads or reagents which react (change ...
test.
Biopsy findings
A kidney biopsy in patients with CFHR5 nephropathy classically shows deposition of
complement C3
Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called ''C3''.
Function
C ...
in the kidney, without any detectable
immunoglobulins
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
there. This is evidence that the disease is caused by a problem with
alternative complement pathway
The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections.
The alternative pathway is one of three complement pathways that opsonize and k ...
regulation, rather than activation of the
complement system
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
by other diseases. In addition, light microscopy often demonstrates histological features of
mesangiocapillary glomerulonephritis. CFHR5 Nephropathy is histologically distinguished from
dense deposit disease
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane ( GBM) thickening, activating complement and damaging the glomeruli.
MPGN accounts for appr ...
by the absence of dense transformation of the glomerular basement membrane – electron microscopy rather reveals
mesangial
The glomerulus (plural glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally s ...
, subendothelial
basement membrane
The basement membrane is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between Epithelium, epithelial tissues including mesot ...
, and occasional subepithelial basement membrane deposits which stain for
complement C3
Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called ''C3''.
Function
C ...
.
Treatment
There is no proven therapy for the CFHR5 nephropathy, although research is currently underway to develop ways of preventing kidney failure developing in those affected.
Prognosis
Over time, kidney failure can develop and most men with the disease will eventually require
dialysis Dialysis may refer to:
*Dialysis (chemistry), a process of separating molecules in solution
**Electrodialysis, used to transport salt ions from one solution to another through an ion-exchange membrane under the influence of an applied electric pote ...
or
kidney transplantation
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
. For reasons which are not understood, women with the disease, although they often have blood in their urine, only rarely develop kidney failure.
The disease has been shown to recur following
kidney transplantation
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
, however in most cases the kidney transplant has a normal lifespan.
References
Further reading
GeneReviews/NCBI/NIH/UW entry on Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II
{{DEFAULTSORT:Cfhr5 Nephropathy
Kidney diseases