Focal and Segmental Glomerulosclerosis and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: a Case Report

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the roots of spinal nerves and peripheral nerves, whose etiopathogenic mechanisms are not well elucidated. This is clinically characterized by symmetrical distal and proximal muscle weakness, decreased or absence of deep tendon reflexes and paresthesias; developed for at least 8 weeks; although; for whose diagnosis electromyographic, histological, imaging and immune criteria are also used. The estimation of the incidence and prevalence of CIDP is difficult due to the heterogeneity in the studies; but it is estimated that the crude incidence is 0.21-0.53 per 100,000 person-years and the prevalence is 1.58-4.39 per 100,000 people.

Extraneural manifestations in CIDP are rare; hepatitis, renal involvement, and autoimmune diseases have been described. Regarding renal involvement, proteinuria has been reported in different ranges with histological pattern of focal and segmental glomerulosclerosis (FSGS) and membranous nephropathy; with or without kidney failure.

Here we describe a case of FSGS associated with CIDP.

Case presentation:

A man in his 40s, with a history of recent diagnosis of high blood pressure, persistent nausea and hyporexia. The physical examination revealed a lucid patient, normotensive with mild paleness, without edema, a diffusely painful abdomen on palpation without peritoneal signs, and adequate urinary flow.

Laboratory tests on admission showed hemoglobin 11 g/dL, urea 142.44 mg/dL, creatinine 11.4 mg/dL (1.5 mg/dL 1 month before and 8.25 mg/dL 4 days before admission), uric acid 9.82 mg/dL, potassium 6.2 mmol/L, pH 7.31, bicarbonate 11.8 mmol/L, calcium 10.68 mg/dL, phosphorus 6.82 mg/dL; LDL cholesterol 131.2 mg/dL, proteinuria 444 mg in 24 hours and urine examination without leukocyturia, hematuria or casts. The rest of the blood count, blood glucose, electrolytes, ANA, ENA profile, ANCA, complement, electrophoretic proteinogram, triglycerides, serology for viral hepatitis and HIV, and renal ultrasound showed no alterations.

Therapy was started with methylprednisolone 1 g IV every 24 hours for 3 days and subsequently prednisone 60 mg every 24 hours, losartan 50 mg every 12 hours, amlodipine 10 mg every 24 hours, and furosemide 40 mg every 24 hours.

A renal biopsy was performed (Figures No. 1 and 2) which described in optical microscopy 14 glomeruli, 01 globally sclerosed, most optically within normal limits, 1/3 with discrete mesangial expansion, segmental rigidity of capillary loops (+/-) and 02 with retraction of the glomerular tuft towards the vascular pole; tubules with cloudy degeneration and hyaline casts, mild multifocal tubular atrophy, tubules with sloughed epithelium and occasionally with regenerative epithelium; interstitium with discrete multifocal inflammatory infiltrate of lymphomononuclear cells and mild multifocal fibrosis; arteries and arterioles with hypertrophy of the muscular layer and mild to moderate subendothelial sclerosis; immunofluorescence was negative. The histopathological conclusion was acute tubular injury. The patient was discharged after 7 days with clinical and renal function improvement (Graphic No. 1).

During follow-up by outpatient consultation, the dose of prednisone was progressively decreased, but an increase in nitrogen levels and proteinuria was evident (Graphic No. 1), so the dose of corticosteroids was increased and a new kidney biopsy was performed 4 months after the first one, also requesting electron microscopy (Figure No. 3). This biopsy described 24 glomeruli in optical microscopy, 03 globally sclerosed and 05 with mild mesangial expansion without hypercellularity; acute tubular injury, tubular atrophy in 60% and interstitial fibrosis and inflammation with mild lymphomononuclear cells; immunofluorescence was negative. In electron microscopy, glomerular basement membrane was observed with partially altered architecture, occasional thickened segments up to 640 nm, focally at the level of the internal rare lamina increased electrolucency, occasionally collapse of loops, slightly increased mesangial matrix, pedicellar effacement in 70% of the capillary perimeter and cytoplasmic vacuolization; tubular and interstitium atrophy with increased collagen fibers. The histopathological conclusion was FSGS.

Four months after hospital discharge, the patient presented symmetrical paresthesias in the extremities, difficulty walking, and hand tremors at rest with a subsequent fall, for which he was hospitalized. The physical examination revealed reduced osteotendon reflexes in the lower extremities and decreased muscle strength in the lower extremities, without sensory alterations or presence of meningeal signs. The examinations showed an electromyography compatible with inflammatory demyelinating polyneuropathy and the sural nerve biopsy confirmed this finding; The rest of the exams were not contributory. Therapy was provided again with pulses of corticosteroids and in the absence of response, 5 sessions of plasmapheresis plus EV immunoglobulin were performed, with favorable clinical response (Figure No. 2); so he was discharged with outpatient evaluation by nephrology and neurology for 2 months.

Discussion

We are facing a patient with no known history of kidney disease who develops a rapidly progressive acute kidney injury with an initial histological finding of acute tubular injury, with response to corticosteroids; presented a relapse and this time with a histological finding of FSGS synchronously associated with the development of CIDP (Graphic No. 1), diagnosed by clinical, electromyographic and histological criteria; with partial response to corticosteroids, plasmapheresis and immunoglobulin.

FSGS is a syndrome that manifests mostly as nephrotic syndrome (54-100%) with multiple etiopathogenesis, including autoimmune; where T cell clones that secrete a vascular circulating factor could increase glomerular permeability to albumin.

CIDP is considered an immune-mediated disorder with unclear etiopathogenesis. Cellular and humoral mechanisms have been implicated, in which activated and autoreactive T cells would cross the damaged blood-neural barrier, intensifying the release of cytokines, activation of macrophages and the phagocytic attack of myelin.

The conccurrence of FSGS and CIDP is rare. Because both diseases may have an autoimmune etiopathogenic basis, it is acceptable to propose that a more generalized autoimmune mechanism is responsible for their coexistence, such as sharing epitopic determinants in the neural and glomerular structure. The presence of autoantibodies against a common neuronal and podocyte structural component, such as neurofascin, has been proposed, which would mediate the neuro-renal condition.

The role that altered erythropoietin production could play in axonal growth and myelin vulnerability has also been proposed; in the case of reduced erythropoietin due to renal dysfunction, the possibility of nerve repair would be affected.

On the other hand, it has been found that the mutation of the INF2 gene, which encodes a formin protein, appears in 75% of cases of Charcot-Marie-Tooth neuropathy associated with FSGS, which could be a link to the damage between podocytes. and peripheral nerve cells.

The final diagnosis of this patient is chronic kidney disease due to FSGS associated with CIDP, probably of autoimmune etiology. This rare association, often not evident, needs to be investigated in depth, as in the initial evolution of the patient presented, since cases of concomitant neuro-renal compromise could remain under diagnosed.