Secondary glomerular diseases typical case reports morphology Doc. MUDr. Zdeňka Vernerová, CSc., MUDr. Martin Havrda

Case 1

Man, 60 years, complaints: Edema of the legs. History of diabetes mellitus with complications: –Retinopathy –Polyneuropathy

Man, 60 years, physical examination: Generalised edema. Severe hypertension common. Signs of chronic diabetes: –Muscular atrophy –Fatigue, poor physical performance –Folliculitis, mycotic cutaneous infections

Man, 60 years, DIAGNOSIS? Diabetic nephropathy.

Man, 60 years, confirmation of the diagnosis? Diabetic vascular abnormalities of the retina. EMG signs of polyneuropathy. Nephrotic syndrome. Loss of GFR common. Renal biopsy.

Man, 60 years, follow-up: Complex approach to treatment: –Tight diabetes control, physical activity, diet –Tight control of hypertension –ACE-inhibitors Early detection and early treatment → better prognosis –Microalbuminuric phase –Normal renal function Poor prognosis in advanced cases –Vascular complicatiations (Stroke, IHD, diabetic foot)

Case 2

Female, 21 years, complaints: 6 months of treatment for migrating arthralgias –Small joints of the hands –Wrists, knees Fever up to 38 deg. Celsius Polymorphic skin rash –Red appearance of both cheeks –Red skin rash on sun exposed areas Dyspepsia, nausea, vomiting

Female, 21 years, physical examination: Erythema of the face (butterfly-shaped) Erythema of sun-exposed areas Edema of some joints Unilateral signs of pleuritis (dull percussion, decreased breathing sounds) Fleeting pericardial friction rub Small aphtous ulcers in the mouth Splenomegaly

Female, 21 years, laboratory tests: ESR 90/120 mm CRP 15 mg/l WBC´s 2, % neutrophils Hgb 70 g/l Trc 90 Urea 15 mmol/l, creatinine 180 umol/l Urinalysis - RBC´s 40/ul Proteinuria 1,7 g/24h

Female, 21 years, DIAGNOSIS? SYSTEMIC LUPUS ERYTHEMATODES Lupus nephropathy

Female, 21 years, confirmation of the diagnosis? Multisystem involvement ARA criteria ANA positive, dsDNA positive, ENA positive, Anti-Ro positive, (ACLA) ↑ IgG ↓ C3, ↓ C4 Renal biopsy – type I,II,III,IV,V,VI

Classification of lupus nephritis I.Minimal mesangial LN II.Mesangial proliferative LN III.Focal LN IV.Diffuse LN V.Membranous LN VI.Advanced sclerosing LN

a If 4 of these criteria, well documented, are present at any time in a patient's history, the diagnosis is likely to be SLE. Specificity is 95%: sensitivity is 75%. Note: ECG, electrocardiography; dsDNA, double-stranded DNA; ANA, antinuclear antibodies. Table 300–2. Classification Criteria for the Diagnosis of SLE a Malar rashFixed erythema, flat or raised, over the malar eminences Discoid rashErythematous circular raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur PhotosensitivityExposure to ultraviolet light causes rash Oral ulcersIncludes oral and nasopharyngeal ulcers, observed by physician ArthritisNonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion SerositisPleuritis or pericarditis documented by ECG or rub or evidence of effusion Renal disorderProteinuria >0.5 g/d or 3+, or cellular casts Neurologic disorder Seizures or psychosis without other causes Hematologic disorder Hemolytic anemia or leukopenia (<4000/ L) or lymphopenia (<1500/ L) or thrombocytopenia (<100,000/ L) in the absence of offending drugs Immunologic disorder Anti-dsDNA, anti-Sm, and/or anti-phospholipid Antinuclear antibodies An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to induce ANAs

Diagnostic criteria of SLE American Rheumatology Association 1.Malar rash 2.Discoid rash 3.Photosensitivity 4.Oral ulcers 5.Arthritis 6.Serositis 7.Renal disorder 8.Neurologic disorder 9.Haematologic disorder 10.Immunologic disorder (Anti-dsDNA, AntiSm, ACLA) 11.Antinuclear antibodies

Female, 21 years, follow-up: Treatment depends on clinical and laboratory assessment and on histologic classification of the disease Prolipherative GN –Immune-supressive treatment Other forms –Antimalarials, steroids Prognosis –Variable, good with systematic treatment –Long (life-long) treatment

Case 3

Female, 65 years, complaints: Strong back pain Edema of the legs Fatigue Weight loss

Female, 65 years, physical examination: Pale skin Tender percussion on vertebral bodies Edema

Female, 65 years, DIAGNOSIS? MULTIPLE MYELOMA with renal involvement. –Amyloidosis –Myeloma kidney –Light chain deposit disease

Female, 65 years, confirmation of the diagnosis? X-ray of the bones Immunoelectrophoresis of serum Bone marrow aspiration (biopsy) Renal biopsy

Female, 65 years, follow-up: Hematologic treatment of myeloma (steroids, cytotoxic drugs, autologous bone marrow transplantation...). Poor prognosis of amyloidosis. In other types of involvement, stabilisation or improvement of renal function is possible.

Case 4

Female, 60 years, complaints: In cold environment – tingeling and dyscoloration of the fingertips (Raynaud phenomenon). Painful cutaneous defects. Edema of the legs and face. Arthralgias. History of hepatitis.

Female, 60 years, physical examination: Generalised edema. Hypertension. Hepatomegaly, other signs of cirrhosis lacking. Palpable purpura. Cutaneous ulcers may appear.

Female, 60 years, DIAGNOSIS? Cryoglobulinemia secondary to chronic hepatitis C, renal involvement.

Membranoprolipherative GN Type 1

Membranoprolipherative GN Type 2 Dense deposit disease.

Female, 60 years, confirmation of the diagnosis: Glomerular hematuria, red blood cell casts Nephrotic syndrome Loss of GFR may appear Cryoglobulins in serum ↓ C3, ↓ C4 AntiHCV positive, HCV RNA positive. Renal biopsy – usually membranoprolipherative GN.

Female, 60 years, follow-up: Treatment of primary disease (hepatitidy) –Interferone α Good prognosis, if hepatitis may be controlled –Symptomatic and supportive treatment –Treatment of hypertension