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The Sézary syndrome (SS) is an aggressive form of cutaneous T-cell lymphoma (CTCL) requiring a rapid diagnosis due to its poor prognosis.We report the first case of an eighty-nine-year-old woman who presented with concomitant Sezary syndrome and anasarca, revealing a nephrotic syndrome caused by a minimal change nephropathy associated with immunoglobulin A (IgA) deposits. Scarce literature described rare cases associating these two entities (nephrotic syndrome and nephropathy). However, the nephrotic syndrome was delayed from disease onset, secondary to immunosuppressive treatment of SS, or due to the weaning of SS therapy. Thus, the direct link between the glomerular lesion and the cutaneous lymphoma was difficult to establish. However, the synchronous occurrence of both SS and glomerulopathy in our patient, along with Sezary cells in both urines (urinary cytology) and biopsy, and resolution of nephropathy after treatment of SS, support the likely attributability of SS in glomerulopathy.Practitioners must acknowledge the possible occurrence of glomerular involvement in SS.

A fifty-one years-old patient with a history of rheumatoid arthritis of recent diagnosis is hospitalized for exploration of a rapidly progressive anasarca state. First analysis discovered an impure nephrotic syndrome (acute renal failure, hematuria) and massive glomerular proteinuria. Auto-medication by nonsteroidal anti-inflammatory drug was revealed. Renal biopsy showed minimal glomerular disease and acute tubular necrosis. Corticosteroid use permitted a normalization of proteinuria and renal recovery was obtained. Literature review showed renal impairment occurring in rheumatoid polyarthritis. Minimal glomerular disease is rare but can be associated with rheumatoid arthritis. This disease, associated with the use of nonsteroidal anti-inflammatory drug, may be responsible of the patient condition.

Idiopathic nephrotic syndrome represents up to 30% of adult glomerulopathies. However, its prognosis according to remission, relapse and renal failure remains unchanged since the 80s and prediction remains difficult. Physiopathology of adult idiopathic nephrotic syndrome is complex and multifactorial, including immunologic and environmental factors and a putative permeability-circulating factor, still unknown. In this point of view, we propose to summarize actual knowledge about idiopathic minimal change disease and focal and segmental glomerulosclerosis physiopathology.

Chronic lymphoid leukemia (CLL) is a hematological malignant disease, associated with a clonal B cell proliferation. The incidence is 4400 new cases per year in France. The prevalence increases with age with a median age at diagnostic of 65 years. Renal involvement is rare and estimated at 1.2% of patients with CLL. Renal pathological diagnoses associated with CLL are variable and are not always related to the hematological disease. We report here on cases of patients with CLL who underwent a renal biopsy over the past 16 years in Marseille.All cases of renal biopsies performed in patients with CLL between2000 and 2016 in Marseille were included. Pathological analysis was performed by the same experimented pathologist. Data were collected at the time of biopsy and after treatment.Ten patients were included in this study. The reason for renal biopsy was acute kidney injury or the onset of nephrotic syndrome. We report on 4 cases of membranous nephropathy, 1 minimal change disease, 1 cryglobulinemia-related membrano-proliferative glomerulonephritis, 1 light chain amyloidosis, 1 fibrillary glomerulonephritis, 1 interstitial monoclonal infiltration and one case of non-specific tubular lesions. Only one patient was treated before the biopsy, 7 patients received a specific hematological treatment of CLL because of its renal involvement. Renal and hematological responses were variable.Renal involvement of CLL is rare and is not mentioned in the Binet classification. Yet, it can be severe, with acute kidney injury or nephrotic syndrome, and can lead to the initiation of a specific treatment. The most frequent presentation this series was secondary MN, which differs from previous series.

Current therapies used in minimal change disease (MCD) were originally designed to cure other diseases. They are only partially efficient, and present inconvenient side effects. Therefore, understanding the molecular mechanisms implicated in the pathogenesis of proteinuria in MCD could lead to new therapeutic strategies. A new experimental transgenic rat model of human MCD was generated. These NPHS2-Angptl4 transgenic rats over-express two different forms of the glycoprotein Angptl4 from the podocyte. The majority of the protein shows a lack of sialylation that is implicated in the pathogenesis of proteinuria. Supplementation of ManNAc, a precursor of sialic acid, significantly reduces albuminuria in those rats by increasing sialylation of the hyposialylated form of Angptl4. After treatment of the first episode of MCD with glucocorticoids in patients, ManNAc could be used as a maintenance drug, especially to reduce the frequency and intensity of relapse. ManNAc is a promising therapeutic agent for patients with MCD.

Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

Focal and segmental glomerulosclerosis (FSGS) is common and non-specific patterns of glomerular injury encountered in human renal biopsies. Cortico-resistant nephrotic syndrome is the main manifestation. We report epidemiological, clinical and pathological aspects of FSGS in Dakar. We report the results of a retrospective study about focal segmental glomerulosclerosis (FSGS) identified from 258 kidney biopsies performed in the medical clinic 1 of A. Le Dantec hospital from January 1993 to December 2003. FSG is found in 134 cases (52%), membranous glomerulonephritis in 32 cases (12,4%), minimal change disease in 20 cases (7.7%). Ninety eigths files were exploitable. FSGS has male gender predominance with a sex ratio of 3. Median age of patients is 28 years (15 and 79 years). Symptomatology is dominated by oedema in 86 cases (87,7%), hypertension in 12 cases (12.2%), hematuria in 5 cases (5.1%), nephrotic proteinuria in 65 cases (66,3%) and no nephrotic proteinuria in 33 cases (33.6%), renal failure in 25 cases (25%)and leucocyturia in 18 cases (18%). FSGS involving more than 50% of glomeruli is encountered in 41 cases (42%), severe interstitial fibrosis is associated in 26 cases. Different pathological aspects are: classical FSGS in 88 cases (88.7%), FSGS " collapsing" in 7 cases (7.1%), FSG "tip-lesion" in one case, FSGS associated to membranous glomerulosclerosis in 2 cases and to diabetic glomerulosclerosis in one case. FSGS is primitive in 88 cases (89,8%) and secondary in 10 cases (10.2%). FSGS is the most common primitive glomerulopathy in Dakar. Nephrotic syndrome is the main manifestation of this disease. Collapsing FSGS is not correlated with the HIV Infection.

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children. While genetic analyses have provided new insights into disease pathogenesis through the discovery of several podocyte genes mutated in distinct forms of inherited nephrotic syndrome, the molecular bases of minimal change nephrotic syndrome (MCNS) and focal and segmental glomerulosclerosis (FSGS) with relapse remain unclear. Although immune cell disorders, which may involve both innate and adaptive immunity, appear to play a role in the pathogenesis of steroid sensitive MCNS, the mechanisms by which they induce podocyte dysfunction remain unresolved. It was postulated that podocyte injury results from a circulating factor secreted by abnormal T cells, but the possibility that bipolarity of the disease results from a functional disorder shared by both cell systems is not excluded. MCNS relapses are associated with an activation of the immune system, including an expansion of T and B cell compartments and production of growth factors as well as many cytokines. Dysfunction of T cells is supported by three main findings: (1) inhibition of a type III hypersensitivity reaction ; (2) defects in immunoglobulin switch ; (3) unclassical T helper polarization resulting from transcriptional interference between Th1 and Th2 transcriptional factors.

If abnormal thyroid function indices have been reported in patients with nephrotic syndrome, hypothyroidism is exceptional.We report three adult patients (1, 2, 3) with hypothyroidism associated with nephrotic syndrome (minimal change glomerulonephritis [1], idiopathic membranous nephropathy stage I [2], stage II [3]). Glomerulopathy treatment and thyroid hormone replacement therapy were both initiated. Low replacement (1, 2) was sufficient when proteinuria decreased. It was higher when nephrotic syndrome was uncontrolled (3).Excessive thyroxine-binding protein and thyroxine urinary loss generate low rate of free thyroxine and elevated TSH. Systematic thyroid hormonal test is necessary if nephrotic syndrome is severe and prolonged.

Immune glomerulonephritis (GN) initially develop as a result of inappropriate immune response, either inadequately directed to self-antigens, or unable to effectively eliminate a foreign antigen. This abnormal immune response leads to the formation of circulating immune complexes, auto-antibodies or self-reactive effector T cells that target glomerular antigens or to the inappropriate regulation of IgA producing lymphocytes (Berger disease) or helper T lymphocyte sub populations (minimal change nephrotic syndrome). In most of the cases, the initial immune injury induces an inflammatory response. However, it is the extent of the interstitial fibrosis which is genetically controlled, that conditioned the evolution of the initial glomerular injury to glomerular sclerosis and progressive renal failure. Recent data on the pathogenesis of the most frequent GN are reported: IgA nephropathy, membranous nephropathy and minimal change nephrotic syndrome. Recent significant advances in the pathophysiology of those glomerular diseases have shed considerable light on the understanding of the underlying disease even if they do not have immediate therapeutic implications.

The various clinicopathological forms of primary glomerulonephritis (GN) in humans include lipoid nephrosis with its histological variants (minimal change disease, focal segmental glomerular sclerosis, diffuse mesangial proliferation, collapsing glomerulopathy), membranous GN, IgA nephropathy, membranoproliferative GN (type I and type II) and crescentic GN. Each of these entities is characterised by pathological, clinical, and immunological features. Although the precise aetiology of primary GN remains unknown, progress has been recently achieved in the understanding of the mechanisms of the glomerular lesions and of their progression. Early diagnosis may lead to adequate treatment and prevention of progressive glomerular damage.

Lipoid nephrosis or idiopathic nephrotic syndrome, the most frequent glomerular disease in childhood, is defined by the association of a nephrotic syndrome and minimal changes on renal biopsy or unspecific lesions such as focal and segmental glomerular sclerosis or diffuse mesangial proliferation. Several complications related to the nephrotic syndrome may occur: infections particularly bacterial infections, thrombo-embolic accidents, hypovolemia with shock. Other complications are secondary to the treatment: steroid therapy, immunosuppressants. The outcome is related to the response to steroid therapy. In case of steroid responsiveness, the risk is the relapse when the steroid dosage is tapered or stopped and the complications related to the treatment which is given to maintain remission. In case of steroid resistance, the risk is that of progression to renal failure which occurs in approximately 50% of patients after 5 years. Moreover, the nephrotic syndrome may recur after renal transplantation.

Clinical and experimental observations suggest that lipoid nephrosis (Minimal change nephrotic syndrome) results from T cell dysfunction due to still unknown mechanisms. By substractive screening library, we identified 84 transcripts, of which 42 correspond to known genes, 12 match with proteins of yet unknown function and 30 are unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the T-Cell Receptor mediated signaling cascades. This includes genes encoding components of the T-Cell Receptor and proteins associated with the cytoskeleton scaffold, as well as transcription factors. During the relapse phase, we have detected very low levels of IL12R beta 2 mRNA suggesting that the T-cell activation evolves toward a Th2 phenotype. Thus, the combination of substractive cloning and differential screening constitutes an efficient approach to identify genes likely involved in the pathophysiology of MCNS.

Clinical and experimental observations suggest that Lipoid Nephrosis (Minimal change nephrotic syndrome) results from T cell dysfunction due to still unknown mechanisms. By subtractive screening library, we identified 84 transcripts, of which twelve match with proteins of yet unknown function and thirty are unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the TCR-mediated complex signaling cascade. This includes genes encoding components of the T cell receptor and proteins associated with the cytoskeleton scaffold, as well as transcription factors such as NF-kappa B and c-maf. During the relapse phase, we have found significant alterations of the NF-kappa B/I kappa Ba regulatory pathway, whereas very low levels of IL12R beta 2 mRNA were detected suggesting that T cell activation evolves toward a Th2 phenotype. We have shown that c-maf is highly induced, shuttling between nuclear and cytoplasmic compartment during the relapse and the remission phases, respectively. Contrasting with the nuclear expression of c-maf, low IL4 levels were detected in relapse. This suggests that the downstream target gene of c-maf in Lipoid Nephrosis, is not IL4 and provides new directions in research leading to identify the target gene, possibly an unknown Th2 cytokine, which might play a critical role in the pathophysiology of this disease. Thus, the combination of subtractive cloning and differential screening constitutes an efficient approach to identify genes likely to be involved in the pathophysiology of MCNS.

Idiopathic nephrotic syndrome (INS) in black African children differs from that of children in temperate areas. The main differences are the high rate of corticosteroid non-responders and the low rate of minimal change glomerulopathy in black African children, possibly related to a racial factor. The identification of a high corticosensibility in certain African regions (Togo and Ghana) can lead to the identification of an ethnic factor. Further genetic studies should be carried out in order to provide a better approach to INS in Africa.

In the very large majority of cases, nephrotic syndrome with minimal glomerular lesions is an idiopathic condition. Drugs can favor the glomerulopathy. The effect of non-steroidal antiinflammatory drugs is well known, but other drugs, particularly tiopronin may be incriminated.A 73-year-old patient developed severe nephrotic syndrome with minimal glomerular lesions 6 weeks after tiopronin therapy was initiated. Complete and spontaneous remission of the nephrotic syndrome was achieved 5 weeks after drug withdrawal. No recurrent lipoidic nephrosis has been observed at 3 years follow-up.Tiopronin-induced nephrotic syndrome with minimal glomerular lesions is usually severe and develops rapidly. Remission occurs rapidly after drug withdrawal. Weekly urine checks with dip-strips should be proposed in patients treated with tiopronin.

Food allergy is becoming more frequent, with 6% of asthmatics reporting an isolated food allergy, and 5 to 6% of atopic dermatitis patients also have either a single or multiple true food allergy. There is value in immuno-biological diagnosis by: Measurement of total serum IgE. Measurement of mono-allergen-specific IgE, following a measurement by a multi-allergen of the Trophatope type. A study of elimination of foods for 2 or 3 months followed by their re-introduction. Oral provocation tests in a hospital environment under clinical control and subsequent measurement of the mediators:-Plasma histamine, tryptase, and urinary methylhistamine to give proof of responsibility of the food allergen. Nowadays, it is perfectly possible to include in diagnosis the new technologies of the test of activation of basophils/or lymphocytes by means of flow cytometry.

To investigate the clinical signs of food allergy is to open new horizons for the understanding of worrying acute symptoms for the patients and too often only symptomatic treatment. It is also possible to take control in a more logical way of illnesses that are classified as chronic and so incurable. The clinical examination requires great attention and much listening. Urticaria, eczema, rhinitis, asthma, colitis are the most frequent symptoms. More rarely, there may be certain migraines or lipoid nephrosis in children.

Food allergy is becoming more frequent, with 6% of asthmatics reporting an isolated food allergy, and 5 to 6% of atopic dermatitis patients also have either a single or multiple true food allergy. There is value in immuno-biological diagnosis by: Measurement of total serum IgE. Measurement of mono-allergen-specific IgE, following a measurement by a multi-allergen of the Trophatope type. A study of elimination of foods for 2 or 3 months followed by their re-introduction. Oral provocation tests in a hospital environment under clinical control and subsequent measurement of the mediators: Plasma histamine, tryptase, and urinary methylhistamine, to give proof of responsibility of the food allergen. Nowadays, it is perfectly possible to include in diagnosis the new technologies of the test of activation of basophils/or lymphocytes by means of flow cytometry.

Immunosuppressive drugs are known to increase the risk of inducing neoplasia, especially acute leukaemia when high doses are used. A case of nephrosis in a 10 year-old boy treated with chlormethine (cumulative dose: 0.8 mg/kg) and chlorambucil (cumulative dose: 10 mg/kg) is reported. Four years after the beginning of the treatment an extraskeletal Ewing's sarcoma occurred. Since the review of literature failed to find any malignancy induced by such an immunosuppressive treatment for nephrosis, the question whether or not this extraskeletal Ewing's sarcoma was attributable to this treatment remains unanswered.

Idiopathic nephrosis, the most common cause of nephrotic syndrome, is histologically defined by minimal glomerular changes, diffuse mesangial proliferation or focal and segmental glomerulosclerosis. The response to corticosteroids carries greater prognostic weight than the histological features seen on the initial renal biopsy. The severity of the condition lies in the risk of relapses which occurs in more than half of cases when steroid dosage is decreased (steroid dependency), then requiring, in case of steroid toxicity, the use of alkylating agents or, more recently, cyclosporine. In 10% of the cases, nephrosis is steroid resistant and the severity of the disease lies in the risk of developing end stage renal failure which occurs in nearly one half of those cases.

Fifty-five cases of glomerular disease in non-diabetic patients above sixty years of age were studied retrospectively. Primary glomerular disease was found in 36 cases, among which 14 cases with minimal changes glomerulopathy (25.4%) and 7 cases with membranous glomerulopathy (12.7%). The remaining 19 patients had secondary glomerular disease, mainly with amyloidosis (12 cases: 21.8%). In these three main forms of glomerulopathy, symptoms were similar, making differential diagnosis impossible before histological examination. Significant responses to treatment can be achieved in minimal changes and extracapillary proliferative glomerulopathies: among the 14 patients given corticosteroids, 9 recovered or experienced very significant improvement. However, one patient under cortico-steroids died from perforation of the sigmoid. In order to establish the best treatment, investigations should be carried out as in younger patients, since they do not seem to involve a significantly higher risk.

Eight children with steroid-response nephrotic syndrome were investigated to study the relation-ship between steroid responsive syndrome, allergy and HLA-antigens. Six of them had clinical and/or biological allergic symptoms. The allergen was identified in four out of six cases (grass-pollen 2 cases, house dust 1 case, frullania 1 case). Six children had DR7 HLA-antigen, five had B12 antigen. Three of the four children with cortico-dependent nephrotic syndrome have associated B12-DR7 HLA antigens. Search of an allergen seems to be of interest in children with steroid-responsive nephrotic syndrome, since eviction of the allergen may be proposed as a complement to cortico-therapy.

Changes in serum protein and albumin levels following resolution of proteinuria were studied in 67 children with nephrosis. These two parameters returned to normal only after the 21st day, i.e. well after the natriuretic crisis and resolution of edema. Our results are consistent with recent studies showing that the fluid and electrolyte changes seen in the urine at resolution of the proteinuria (increased diuresis and natriuresis) are not due to a return to normal of serum protein and albumin levels. They probably reflect correction of an intrarenal abnormality whose mechanism is unclear.

Measurement of serum C3 does not provide precise informations concerning an eventual consumption of this complement component during an immunological process. An increased synthetic rate may compensate an accelerated catabolism. The study of breakdown products of C3, such as C3d is a more sensitive approach of the role of complement in some immunological disorders. Therefore C3d was measured in the serum of patients with chronic non systemic glomerular diseases. High values of serum C3d were found in all cases of hypocomplementemic glomerulonephritis. Circulating C3d was also increased to a lower extent, in patients with normocomplementemic nephritis such as minimal change disease, mesangial nephritis with IgA deposits and membraneoproliferative (type I) glomerulonephritis. The data suggested the involvement of complement in a number of glomerulonephritis. Participation of complement in immunological disorders particularly in chronic non systemic glomerulonephritis could require a reevaluation when functional tests are performed in addition to static measurements.

Circulating immune complexes (CIC) account for a majority of GN. Their pathogenicity depends on size, molecular composition, glomerular hemodynamics and activity of phagocytes. The phagocytic function of peripheral monocytes was studied in 23 patients with non-systemic active GN and in 16 GN in complete remission. Phagocytic activity of peripheral blood monocytes was assessed in vitro, by calculating phagocytic index (IP: number of zymozan particles in each monocyte) and phagocytosis percentage (PP: number of phagocyting monocytes); the tests were carried out on autologous and heterologous serum samples. In 13 controls, PP was 79 +/- 5.8%. In 7 membranous GN, 6 membranoproliferative GN and 10 lipoid nephrosis, PP was severely decreased, 63.4 +/- 9.6%, 52.1 +/- 19% and 52.2 +/- 14%. In each group of GN, these results were significantly different from controls (p less than 0.01). In all groups these results were similar in autologous and heterologous serum samples (55 +/- 13% and 57.5 +/- 16%; NS). This perturbation was not observed in GN in complete remission. Therefore, this defect was not linked to the presence of serum inhibitors. In conclusion, alterations of phagocytic activity is present in some primary active GN and may explain an insufficient rate of CIC removal.

Classically, the histological lesion observed in a drug-or heavy metal-induced nephrotic syndrome is membranous glomerulonephritis. We report two cases of "toxic" nephrotic syndrome with unusual histological features. One was secondary to mercury intoxication and the other, to D-penicillamine in a patient with rheumatoid arthritis. In both cases, renal biopsy revealed minimal glomerular changes. The proteinuria rapidly disappeared after exposure to the toxic agent was discontinued. Genetic factors and a disregulation of the immune system with lymphokine production may be responsible for these renal changes. This study demonstrates that renal biopsy is necessary in this clinical setting.

A 65 year old woman had a minimal changes nephrotic syndrome (MCNS) with steroid-induced remission. An underlying malignancy was discovered at the time of relapse of proteinuria: it was a retroperitoneal chordoid sarcoma. Even though the tumor could not be excised, complete remission was again observed with corticosteroids. There was no second relapse when prednisone was discontinued and during the seven months before the patient died. This is a new unusual case of MCNS associated with carcinoma. The response of nephrotic syndrome steroid therapy is further suggestive evidence that deficiency in T-cell function may be involved.