Renal involvement in systemic diseases

Lívia Jánoskúti

Introduction

A variety of systemic conditions can affect the function of the kidneys, from acute illnesses (including for example prolonged hypotension) to drugs and more insidious illnesses.

Overview of the potential renal consequences of some of the commoner/more important systemic diseases.

Renal involvement in systemic diaseses

1. Hypertensive nephropathy/nephrosclerosis2. Metabolic disorders (Diabetes mell., gout)3. Immunologically mediated diseases4. Diseases associated with paraproteinaemia

and neoplasia5. Hereditary disorders

1.Hypertensive nephropathy

• ¼ of patients with renal failure has hypertensive nephropathy

• Chr.hypertension damages the renal vasculatureIschaemia and hyperfiltration cause nephrosclerosis

• Hypertension is a risk ofCholesterol embolisationstenosis of renal arteries

• More than 10 years history of hypertension

Think of hypertensive nephropathy,if

• The patient african or karibien origin• The patient has hypertensive retinopathy• There is left ventricular hypertrophy on the ECG • There is a long history of malignant

hypertension/hypertension• The proteinuria<0,5gr/die• Renal biopsy showes nephrosclerosis

What to do in hypertensive nephropathy?

• Blood pressure control with ACEI /ARB, diuretics and other drugs.

• No ACEI in bilateral art. renal stenosis!• Control of renal function if you change the dose of

a drug.• Treat cardiovascular risk factors (cholesterol,

obesity, smoking etc.)• In significant renal art. stenosis- renal

angioplastic.

2.Metabolic disorders/ Diabetes mell.

• 30-40% of patients with end stage renal disease have DM.

• In type I.DM- common, in type II.-not common

• 3% of patients with >10 years history of DM. have D. nephropathy

• Nephropathy is a risk factor for other micro-and macrovascular complications .

2.Characteristics of diabetic nephropathy

• Microalbuminuria 20-300mg/die- incipiens sign of nephropathy

• >300mg/die – diabetic nephropathy.• GFR gradually decreases• Blood pressure increases

2.What to do in diabetic nephropathy?

• Tight glycemic control with diet, drugs ( insulin) and regular physical activity.

• Tight RR control 130/80 with ACEI/ARB ± diuretics/BB

• ACEI improves the prognosis of patients with microalbuminuria in normotensives as well.

• Treat other cardiovascular risk factors( aspirin, statin)

• Pancreas and renal trasplantation

2. Metabolic disorders/Gout

Cause:10% uric acid overproduction, 90% decreased renal excretion

1.Acute uric nephropathy-urate deposition in renal tubules- lympho.,-myeloprolif. diseases – prevention:increased fluid intake ,+ 600-900mg/die, later 300mg/die allopurinol

2.Chronic uric stone -nephropathy- uricosuric treatment: probenecid 2x250mg /die ,or sulfinpyrazon 2x500mg/die later 300-400mg/die.

Tophus in the kidney

3.Immunmediated kidney diseases.

1. SLE2. Goodpasture syndrome3. Vasculitic syndromes4. Rheumatoid arthritis5. Scleroderma6. Sjögren syndrome

SLE

3/1.SLE and the kidney

• Common:35-90%• Clinical symptoms:mild abnormalities of

the urinary sediment to massive proteinuria and from chronic indolent GN-itis to rapidly progressive renal failure

• Clinical types:nephrosis( 50%), nephritis, mixed forms,some % rapidly progressiveGN

RPGN- crescent formation

SLE-kidney-treatment

• Milder forms-treatment directed to control of the extrarenal manifestations( steroids in modest doses, salicylates(!),antimalarials.Serologic parameters should be followed –antiDNS,C3,4.

• Severe forms(IV):high dose iv metilprednisolon, adjunctive cytotoxic agents( cyclophosphamide, azathioprine)

• Uremia:chr.dialysis, kidney transplant.(uncommon the recurrence of the SLE in the allograft)

3/2.Goodpasture syndrome

• Antibody against glomerular basement membrane• Affects young men• Pulmonary hemorrhage, iron deficiency

anaemia,progressive renal failure• AntiBM AB 90% positive, histology: IF-linear

deposits in basement membrane• Early treatment is effective: plasmapheresis +high

dose steroid, later dose reduction + cytotoxic drugs

AGBM glomerulonephritisLinear deposits

Schönlein Henoch purpura

3/3Schönlein Hennoch purpuraHypersensitivity vasculitis

• Vascular purpura, abdominal pain arthralgias,hematuria, proteinuria

• IgA increased ,IC contains IgA• Prognosis is usually good.Steroid,cyt.is not

evidently helpful. In severe forms plasmapheresis +steroid, immunsuppression.

3/3 .Necrotizing vasculitis

• Wegener granulomatosis( upper-lower airway granulomasa+ kidney)

• Microscopic polyangiitis ( pulmonary infiltrates,RPGN, muscle-nerve abnormalities)

• Churg-Strauss sy (allergic asthma ,eosinophilia, kidney)

ANCA positivity• Polyarteritis nodosa (fever, headache, myalgia,

hypertension, renal involvement)• Prognosis usually bad.• Treatmnet in severe cases: plasmapheresis, steroid

cytostatic drugs.

1.Wegener gran.(No linear deposits)2.Goodpasture (Linear BM deposits)

Rheumatoid arthritis

3/4.Rheumatoid arthritis and the kidney

Several form of glomerular injury occure:• Amyloidosis• Nephrosis sy- complication of

penicillinamin / gold therapy)• Papillary necrosis-analgetic drugs side

effect• Vasculitis-mild proliferative or

membranous GN

Sjögren syndrome

3/5. Sjögren sy

• Incidence:5% • Types: glomerulonephritis, interstitial

nephritis ( polyuria, nephrolithiasis), renal tub. acidosis.

Scleroderma

3/6. Scleroderma

• Microangiopathy lead to acute or chronic renal failure

• Acute form: sudden skin symptoms, hypertension, headache,oliguria,edema, renal failure.

• In spite of ACEI treatment 50% renal failure.

• Remission can occure .

4.Paraproteinaemias and the kidney

Myeloma multiplex ( plasma cell tu): 50%of cases have kidney involvement

Causes of renal failure:• Dehydration, hyperviscosity• hyperCa• NAIDS, biphosphonat side effect• Tumor lysis syndroma• Amyloidosis• Light chain deposition.

4.Paraproteinaemias and the kidney

Amyloidosis( primer):deposits that stain with Congo red,

nephrosis sy 5 years survival 20%, no effective treatmentCryoglobulinaemiaCryoprecipitable Ig-k, form IC(IgGpolyclon, IgM)Acute renal failure, RPGNOften associated with hepatitis C infection

(interferonalfa) plasmapheresis,steroid ,cytostatic drugs

Tumors and kidney

Nephrotic syndrome is the most common clinical manifestation

• Secunder amyloidosis• IC mediated membranosus GN,which

regresses after removal of the tumor

5.Hereditary disease and kidney-Sickle cell disease

• The disease causes a glomerulopathy with proteinuria and progressive renal insufficiency, leading to ESRF; renal papillary necrosis is another possible mechanism of acute renal syndromes.

• Albuminuria is a sensitive marker of glomerular damage and precedes the onset of renal failure.

• There are no effective therapies to prevent the onset of renal failure other than good management of the condition in order to reduce the incidence of, and ameliorate, sickling crises.

• Great care should be taken to avoid or adjust the dose of nephrotoxic drugs which may precipitate acute or acute on chronic renal impairment.

• Those with ESRF will require renal replacement therapy and should be considered for transplantation.

Main message

If you detect • Urine abnormality• Renal function abnormalityAlways look for• Urological disease• Systemic disease with renal involvement• Intrinsic renal disease

Case: B.A.(17 years old female)

• 1989.Small joint pain, hair loss• Physical examination: small joint involvement, RR 120/80

P:100/min No edema.• Labor: spec. grav 1015 protein:+++ Sed:6-8wbc,10-15 rbc

24h prot: 2,6gr ELFO albumin, transferrin.Se prot:53g/l Alb 53% kreat 93uM/l , ANF.antiDNS pos Cryoglob pos C3 decreased

• Kidney biopsy: mesangioprolif.GN• Therapy:250mg Metypred• Proteinuria decreased to 1,2g/24h, hematuria stopped

Case: SZ.M.(32 years old female)• 1984.weakness, fatigue,small joints pain,back pain,

alopecia, photosensitivity,periorbital, hand leg edema for 2 month.

• Physical examination:pallor,leg and hand edema,RR 120/80 P:90/min

• Labor: urin 1022 prot+++ Ül: 2-4wbc 80-100rbc Ht 0,29 WE:104mm/h 24h prot 16gr Se prot.43g/l Alb 33% Se chol:7,2 urine ELFO: alb, trasferrin, IG-k kreat 65uM/l ANF , antiDNS poz.,C3 decreased

• Biopsy: membranoprolif.GN. Th 50mg Prednisolon+100mg Imuran After 6 m. 24h prot.6gr, Se prot.59gr/l Ül:1-1 rbc

Case:K.L.(65 years old male)

• 1991.Back pain X ray:diffuse osteoporosis,Th7 compres.fract. We:24mm/h Ht 0,31 Treatment:Ca.D3 Miacalcic

• 1992.febr. Dysuria,problems with stool-spinal MRI- tu-200Gy telecobalt irrad.

K.L.• 1992. July Pallor, painfull ribs and dorsal vertebrae• Phys. exam:pallor,RR 70/90 P:94/min• Labor: fs 1020 prot:+++ Sed: negSü:70mm/h Ht 0,31 fvs 500024h prot 3,6gr ELFO: kappa light chain, Se ELFO: M

comp.5,4g/l BUN 22 kreat 480Bone marrow: 20% atypical plasma cell. Treatment:BCNU,Cyclo.,Vincrs. PrednisolonAfter 3 course of treatment: urin prot..0,58g/24h kreat

176uM/l,normal urination, and stool, bone pain decreased

S.E.• 59 years old man• 2002.AMI ,hypertension• 2014. Juny: macroscopic hematuria,- cystoscopy

revealed urin bladder tu.• He is on 25ug Thyroxin therapy• 2014.July. Surgery was planned, but, because of

pleural effusion, generalized edema, dyspnoe,anaesthesiology contraindicated the operation.With the suspition of heart failure patient was transported to our department.

S.E Physical examination.

• Obes (110kg 178 cm), around the umbilicus 20 cm diameter red plaque(itching,for a month it showes a growing tendency), pitting leg edema, 4 cm bilateral pleural effusion

• RR 160/90 P 80/min rhythmic, aeq.

SE imaging results

• Chest Xray: pleural effusion. No heart enlargement.

• Echocardiography: EF54% LVH (Se, LWPD 13) relaxation abnormality.

• Abdominal US: normal kidneys norm.Tumor in the urin bladder.

S.E. Lab tests

• BNP 145pg/L• Ht 0,41 cu 7,1 cholesterol 8,18 LDL 5,7)

CRP 3,6mg/ml• SGOT,GPT SAP norm• creatinin 263-270-231• Urin test:spec.grav 1015, protein ++++ ubg norm

Sediment 80-100rbc, 20-25 wbc, bact• Se ELFO: 37,5 g/L Albumin 16,8 gr/L• 24h urine protein: 8 gr

S.E.Suspected diagnosis

• Tumor associated (paraneoplastic) nephrotic syndrome