What is FOCAL GLOMERULOSCLEROSIS

Focal glomerulosclerosis (FGS) is a sclerous lesion of part of the renal glomerulus, which is at first present in some glomeruli and then gradually spread to all the glomeruli of the kidneys.
In the clinical context of the cortico-resistant nephrotic syndrome, the discovery of a FGS lesion represents a negative prognostic element and characterizes children who very often quickly develop an end-stage renal disease (ESRD).
As far as the causes and mechanisms that lead to FGS, some forms of cortico-resistant nephrotic syndrome have been recently identified as due to hereditary defects in the synthesis of the proteins of the basal glomerular membrane; therefore the spectrum of possible causes, previously confined to cellular immunological factors, has been extended and probably not concluded yet.
Consequently, it is likely that different diseases hide behind the term FGS, and the determining factors are known only for some of them. A more precise diagnosis according to the categories known up to now represents then a first step to plan an individualized treatment.
It is in fact known that patients with genetic defects don’t respond to therapy with corticosteroids, nor to the immunosuppressive one: a diagnosis of a genetic kind would consequently allow to avoid long pharmacological treatments burdened by severe side effects. Transplant is instead the most rational therapy for these patients. 
For patients with FGS from immunological factors, the possible therapeutic solutions currently adopted imply on one side the immunosuppression of the cellular lines producing lymphokines, on the other side the elimination through plasmapheresis of the plasmatic factors responsible for the damage.
The outcome of the different treatments proposed hasn’t been conclusive though, at least for patients with severe manifestation of the disease. In these cases, in fact, FGS recurs in the transplanted kidney and they have to go back to dialysis again, which is why this disease is defined as incurable.
The main directions of research that will be developed with the help of the Foundation “La Nuova Speranza” emerge from what has been said: genetic diagnosis of the different forms of FGS, study of the cellular population responsible for the disease and formulation of an immunosuppression protocol with new and more specific drugs.

Dr. Alberto Edefonti, founder, Consultant of the Department of Nephrology, Dialysis and Renal Transplant at the “De Marchi” Clinic, Milan. 

some pictures

Here's the glomerulus, the traffic warden of our kidneys.

A ball of capillary vessels through which the blood is filtered.  

Ecco il glomerulo, il "vigile urbano" del rene

How to recognize focal glomerulosclerosis
1) Signs and symptoms:
Focal glomerulosclerosis (GSF) usually presents itself on a clinical level with a picture of nephrotic syndrome.
This syndrome shows itself mainly through:

    1. Proteinuria: a significant urinary loss of proteins (>3,5 g/day), which causes a consequent hypoprotidemy (low levels of proteins in the blood) and specifically hypoalbuminemia (low levels of albumin in the blood).

    2. Oedema: an increased amount of fluids outside blood vessels or cells. It typically occurs to the eyelids in the morning or to the ankles in the evening (declivous oedema). It’s a consequence of proteinuria and hypoalbuminemia. One of the functions of the proteins in the blood is infact to contribute to the balance of spaces and volumes of body fluids (oncotic function of the proteins). The oedema is also caused by the retention of sodium, which happens when the kidneys attempt to restore the right volumes of body fluids: nevertheless, it actually causes extra water retention.

    3. Oliguria: a significantly decreased production of urine (< 200-250ml/m2/day).

    4. Hypertension: an increase of the blood pressure. In the GSF, this is due to the sodium retention and other compensation mechanisms carried out by the kidneys.

    5. Predisposition to infections: subjects affected by nephrotic syndrome or GSF risk to contract different kind of infections, because antibodies (Ig) are lost together with proteins.

    6. Thrombosis: the formation of blood clots inside blood vessels. It’s partially due to the urinary loss of proteins that have an anticoagulant function, and partially to the massive synthesis of a protein (fibrinogen) with a prothrombotic function. Furthermore, an alteration of the activity of blood platelets can happen in the GSF.

    7. Alteration of the bony metabolism: due to the decrease of calcium in the blood (hypocalcemia) consequent upon the hypoalbuminemia, but probably also due to secondary hyperparathyroidism (increase of parathormone in the blood, a hormone that increases the level of calcium in the blood) and to a modified metabolism of the D vitamin. . 

2) Tests to undergo:
In case there is a suspicion of nephrotic syndrome and/or GSF, the following controls have to be carried out:

  • Urine test and urine collection over a day: it shows a significant loss of protein, over 3,5 g/day or 40mg/m2/hour. Sometimes, there can be microhematuria (blood in the urine). The urinary deposit contains cylinders that can be hyaline, granular, fat or amyloid and cylinders of epithelial cells.

  • Blood test: it shows the overall loss of proteins (< 6gr/dl), and specifically the decrease of albumin (<2.5g/dl), the relative increase of the alpha-2 and beta-2 globulins with reduction of the gamma globulins, the increase of cholesterol, triglycerides, of LDL and VLDL (hyperlipidemia), the increase of fibrinogen, of the coagulation FV and FVII, of the number of platelets, the reduction of antithrombin III, hypocalcemia (reduction of the level of calcium) and the decrease of D3 vitamin.

3) Renal biopsy:
When a subject with nephrotic syndrome doesn’t respond to the standard treatment, it’s usually suggested to undergo renal biopsy, which is the only way to surely diagnose GSF.

4) Current treatments:
Besides the symptomatic treatment (hyposodic diet, antihypertensive drugs, diuretics, antiaggregants), the therapy centres on drugs that stop the autoimmune reaction.

  • Among these drugs, the preference goes to the corticosteroid. It has to be mentioned, though, that only part of the subjects respond to this therapy, while others show resistance to corticosteroids. Some others can also develop a corticosteroids dependency. Patients who don’t respond or partially respond to the steroid are treated with immunosuppressive drugs, as cyclosporine, tacrolimus, mycophenolate mofetil, or cytostatic drugs, as cyclofosfamide associated or not to plasmapheresis cycles. Besides, they are treated with drugs that slow down the progression of the renal disease preventing renal fibrosis, as the ACE inhibitors and the Angiotensin II receptor antagonists, the non dihydropiridinics calcium antagonists. Some cases of GSF don’t respond to pharmacological therapies, therefore the disease progresses to the end-stage renal disease (ESRD). In these cases it’s necessary to undergo a substitutive dialytic therapy and to confront a renal transplant if necessary. It has to be mentioned though that GSF tends to recur in the transplanted kidney in 50% of cases at the first transplant, in 90-100% of cases if the first transplant has already failed because of relapse.

This is a popular scientific document with no medical or scientific value. Each case of FGS has to be assessed and treated by a nephrologist.