Nephrology

Urine analysis; physical exam Appearance; colour, odour. Sp Gravity; n= 1003 1030 Chemical exam; pH, protein, glucose, ketones, bl, urobilinogen. Microscopic exam; crystals, casts, cells, organisms. NB; nitrite test detect G ve Bact. leukocyte esterase detect WBC (5-15/HPF) RBC casts acute GN ( nephritic) wbc cast interstitial N, pyelon. tubular cell cast ATN. Granular cell cast chronic GN, pyelo. hyaline proteinuria fatty Nephrotic hematuria = rbcs > 3. pyuria = wbcs > 4.

Red urine
Hematuria. Hemoglobinuria. Myoglobinuria. Porphyrins. Drugs; MD, L-dopa, desferoxamine, metronidazol. Cyclophosphamidehgic cystitis, Beetroot,. Orange brown; direct bil, drugs; phenazopyridine, nitrofurantoin, Fe, B1, rifampicin, phenytoin.

Approach for hematuria

If heavy proteinuria >1 gm/24h , RBCs casts , dysmorphic RBCs >70% glomerular serology, KFTs, U/S, renal biopsy. If proteinuria <1 gm/24h, no RBCs casts, dysmorphic RBCs <30% Non glomerular urine cytology, spiral CT or IVP, cystoscopy, or MRA. In between manage according to clinical & lab clues e.g.; PT, PTT, TB test, PCR for TB, urine Ca.

Approach for proteinuria

If proteinuria >2 gm/24h, hypoalbuminemia, dysmorphic RBCs glomerular serology, renal biopsy. if K, P, uricemia, glucosuria, aminoaciduria tubular urine B2 microglobulin, heavy metal screen. If proteinuria >2 gm/24h,disparity bet dipstick & prot/creat, anemia , Ca , globulins overflow (= plasma LMWP as MM, Hb, myogl urine electrophoresis, BM biopsy, radiological survey.

Functional proteinuria
Causes fever. Exercise. Congestive heart failure (renal ischemiaAgII). Orthostatic proteinuria; - young male - Regress in 5-10 yrs. - Diagnosed by early morning sample & by 12 hrs ambulatory & 12 hrs overnight.

Choice of imaging procedure

RAS. - for screening duppler, MRA, CTA. - to assess function ACEI renogram (renal scan) Chronic pyelonephritis & reflux nephropathy IVP, DMSA scan. Medullary sponge IVP. Neoplasm US , CT, MRI for staging.

Dynamic renal scans are used to;

1) Measure GFR DTPA. A split GFR can be obtained for each kidney, which is not possible with the creatinine clearance method. 2) Assess renal blood flow (RBF) in

patients with suspected renal artery stenosis hippuran/ MAG3 + ACEI renogram.

3) differentiate between obstructive versus non obstructive causes of hydronephrosis MAG3 + Lasix renogram.

Lasix renogram
Outflow delay Parenchymal Normal transit time (PTT) after = immediate fall in time IVI of 40 mg activity curve frusemide Non obstructive dilatation +++ Obstructive dilatation +++ delayed = .fall less .does not fall

2) Static renal scan

It consists of imaging of a radiotracer (dimercaptosuccinic acid =DMSA) that is taken up & retained by the renal proximal tubular cells, providing a static image of functioning nephrons. Value,. 1. renal size, position, and axis. 2. focal renal parenchymal abnormalities, e.g. scars appear as bites.

 1. 2. 3. 4. 1. 2. 3. 4. 5. 1. 2. 3. 4.

Renal biopsy
Indications; Nephrotic S Unexplained RF with normal Kid size. Failure of recovery from ARF. Asymptomatic prot., hematuria. Contra indications; Obese, oedema. Uncontrolled HTN. Bleeding tendency. Shrunken kid. Single kid except transplanted. Complications; Pain, hematoma, hematuria(in 20%, severe in 1-3%, need intervension in 1;400) AV aneurysm in in 20% but insignificant. Infection Mortality 0.1%.

Glomerulopathies

Normal Glomerulus (PAS)

Granular mesangial

Linear Capillary

Granular

Clinical Presentations
* Asymptomatic proteinuria * Nephrotic syndrome * Nephritic syndrome * Hypertension * Hematuria which may be microscopic or macroscopic * rapidly progressive renal failure * chronic kidney disease.

Rapidly Progressive GN (or Crescentic) - Pauci-immune ( ANCA associated Gn) =

- idiopathic cresentic. - Microscopic Polyangiitis - Wegener's Granulomatosis - Churg-Strauss Syndrome. - Immune complex e.g Post Streptococcal, IEC, lupus nephr. - Goodpastures.

Hematuric Syndromes (Isolated Hematuria,

nephritic, or RPGN)
-Mesangioproliferative GN (eg, IgA nephropathy) -Focal proliferative GN (eg, lupus nephritis WHO III, infective endocarditis)

Proteinuric Syndromes (Isolated Proteinuria, Nephrotic) -Minimal change disease -Focal and segmental glomerulosclerosis(FSGS)
-Membranous nephropathy

Nephritic and Nephrotic Features

-Membranoproliferative GN -Mesangial proliferative GN -Fibrillary glomerulopathies -Hereditary nephritis (Alport syndrome)

-Diffuse proliferative GN -Diabetic glomerulosclerosi (eg, post- streptococcal GN, lupus nephritis WHO IV) -Amyloidosis. -Crescentic GN ( severe IC, pauci-immune nephritis, -Light-chain deposition disease

anti-GBM nephritis)

What is this lesion encroaching the glomerular tuft. What serious clinical condition is it associated with
Slide no 14

normal

Crescentic GN - (Trichrome Stain)

IgA Nephropathy

(Berger dis)

one of the most common forms of GN worldwide. male /female 2/1. 2nd and 3rd decades of life. Causes, -1ry -2 ry;, celiac, dermatitis herpetiformis, IBD, psoriasis, alcoholic C ankylosing spondylitis, mycosis fungoides, HIV. - familial. Pathogenesis; IgA deposited in the mesangium(polymeric , IgA) C/P; children synpharyngetic macroscopic hematuria during adults asymptomatic microscopic hematuria. Prognosis; benign disease , progression to renal failure in 25 30% over 2025 years; Recur in 50% posttransplant but good Graft survival.

 IF: mesangial IgA and C3 IgG or IgM

IgA Nephropathy

40 to 50 %
hematuria

30 to 40 %
CKD + proteinuria,

<10 %
Acute or RPGN.

No Treatment Monitoring /6 -12 m.

progressive or severe disease. 0.5 - 1g/day 1.0 -3.5 g/day

( s creat. >1.5 mg/dL,or rising , a GFR decline>15% /y, nephrotic proteinuria, marked proliferation without crescents

As RPGN

ACEI & ARBS + fish oil + statins.

6-months course of steroids

Combined immunosuppressives ; prednisone + cyclophosphamide for 2 yrs.

What is this disease in a patient with abdominal pain, hematuria, and renal impairment and a palpable rash on thighs What is the most common glomerular lesion on light microscopy of this patient when a biopsy is taken

Slide no 11

Henoch-Schnlein purpura
distinguished clinically from IgA nephropathy by; - prominent systemic symptoms, - a younger age (<20 years old), - preceding infection, and - abdominal complaints. C/P; skin, arthritis, abd pain, Renal. Ttt; arthralgias NSAIDs, severe abd pain, renal steroids.

Poststreptococcal Glomerulonephritis acute endocapillary proliferative glomerulonephritis ages of 2 -14 years, throat infections with particular strains of streptococci (nephritogenic strains); After impetigo by 26 weeks and 13 weeks after pharyngitis. subepithelial "humps. C/P; acute nephritic picture C3 with normal levels of C4. TTT; eradication of infection. Postinfectious glomerulonephritis can occur in patients with Subacute Bacterial Endocarditis, ventriculoatrial and ventriculoperitoneal shunts; pulmonary, intra-abdominal, pelvic, or cutaneous infections; and infected vascular prostheses.

ANCA associated GN

pauci-immune glomerulonephritis
C-ANCA= anti-proteinase 3 (PR3) in Wegener's P-ANCA= anti-myeloperoxidase (MPO) more common in microscopic polyangiitis, and Churg-Strauss syndrome. TTT; Induction therapy usually includes some combination of methylprednisolone, and cycloph. plasmapheresis in case of pulm hge. Maintenance, steroid tapering & give cyclophosphamide for up to 2 years after remission.

1) Idiopathic Crescentic GN

Renal-limited glomerular capillaritis Pauci-immune crescentic GN. Both pANCA and cANCA +ve. 2) Microscopic Polyangiitis Renal + systemic vasculitis. 3) Wegener's Granulomatosis Renal + vasculitis + granulomas nasal ulcers, sinus granuloma, hemoptysis CXR...... nodules , cavities. Biopsy of involved tissue small-vessel vasculitis and noncaseating granulomas. 4) Churg-Strauss Syndrome Renal + vasculitis + granulomas + eosinophilia. Asthma, fleeting pulmonary infiltrates May be associated with leukotriene receptor antagonists.

Antiglomerular Basement Membrane Disease

Autoantibodies directed against GBM collagen IV. focal or segmental necrosis with crescent. IF; linear immunofluorescent staining for IgG TTT; 810 treatments of plasmapheresis accompanied by oral prednisone and cyclophosphamide in the first 2 weeks.

Goodpasture Syndrome:

 Causes of pulmonary-renal S;
1. 2. 3. 4. 5. 6. Microscopic Polyangiitis. Wegener's Granulomatosis. Good pasture $. SLE. Churg-Strauss Syndrome. HSP, cryo.

Membranoproliferative GN=mesangiocapillary GN
Types;
Type I Disease (Most Common) 1ry. 2ry; SBE, SLE, HCV, cryo, HBV, solid malignancy. Type II Disease (Dense Deposit Disease) C 3 nephritic factor-associated Partial lipodystrophy Type III Disease Idiopathic Complement receptor deficiency

Pathology;
1. 2. 3. 4. Subendothelial deposits mesangioproliferative changes mesangial interposition between the capillary BM and endothelial cellsThickening of the GBM with a double contour . lobular segmentation

Lab: low serum levels of C3 are typical.

TTT; Long term alternate day steroids (prednisone 2 mg/kg) for one year, followed by slow tapering to a maintenance dose of 20 mg every other day for 3 to 10 years. The role of aspirin and dipyridamole is unclear. DD of MPGN; cryoglobulinemia Lupus nephritis class IV.

Nephrotic Syndrome
Heavy proteinuria> 3.5 gm/d/1.73 m2, minimal hematuria, hypoalbuminemia, hypercholesterolemia, edema, and no hypertension. TTT; lipid-lowering agents diuretics inhibitors of the renin-angiotensin system can lower urinary protein excretion. +/- anticoagulants.

1. 2. 3. 4.

Minimal Change Disease

7090% of nephrotic syndrome in childhood but only 1015% of nephrotic syndrome in adults. Causes; 1 ry or 2ry to Hodgkin's disease, NSAIDs, IFN, IMN, lead. Lab; selective proteinuria= LMWP. Pathology; LM, IF=nil EM=effacement of the foot process. TTT: 1. Prednisone 60 mg/m2/d for 4 wks then 40 mg/m2/d for 4 wks then gradual
tapering over 4 wks.

2. and other immunosuppressive drugs, such as cyclophosphamide, chlorambucil, and mycophenolate mofetil, are saved for frequent relapsers, steroid-dependent, or steroid-resistant patients. Prognosis; complete remission (<0.2 mg/24 h of proteinuria) Relapses occur in 7075% of children after the first remission steroid-dependent=relapse as their steroid dose is tapered. steroid-resistant patients fail to respond to steroid therapy.

 Causes; 1 ry =70-80%. 2 ry; - Malignancy; solid, NHL. - Infection; HBV, HCV, P malari, S, leprosy. - syst; SLE, MCTD, sickle. -drugs; gold, penicillamine, captopril. Patho; LM& EM Thick BM, supepithelial deposits. IF; granular Ig G, C3 Prognosis; 40% spont remission 30% persistant proteinuria 30% progress to RF. need cytotoxic therapy TTT Alternate monthly for 6-12 months; - pulse steroid then 0.5 mg/kg/d - chlorambucil or oral cyclophosphamide.

Membranous

Membranous GN :

Focal Segmental Glomerulosclerosis

segmental glomerular scars in some glomeruli. 1/3 of cases of nephrotic syndrome in adults and 1/2 of cases of nephrotic syndrome in African Americans. poor outcome in; - Nephrotic range proteinuria, - African-American race, - renal insufficiency. Causes; 1. 1ry 2. 2ry - genetic (cong nephrotic S, steroid resistant, familial FSGS, Alport, Nail & patella) - infection; HIV ,Parvo B19 , Bilh. - drugs; Heroin, lithium, pamidronate. - Glom. HTN dt long standing nephron loss; sickle, single, obesity, HTN, rejection, reflux.

PAS

perihilar

 Path; LM; FSGS. EM; 1rydiffuse efface of foot process. 2 ry patchy efface of foot process. IF; -ve except for Ig M & C3 trapped in sclerotic lesions TTT 2ry as any nephrotic, TTT of the cause. 1ry steroid 1mg/kg/d for 3-4 months then - if complete responsetaper after 1-2 wks over 3 months. - if partial response (>50%)taper over 6-9 months. - if little response add cyclosporin & switch to alternate day then taper over 3 wks.

Hereditary nephropathies ALPORT'S SYNDROME & Thin GBM

Transmisson; 1) 80%XL -------------------------- Alport, Thin GBM = mutation in type IV collagen fibrils fragile GBM. 2) 15%AR, --------------------------- homozygous Alport , heterozygous Thin GBM mutation in type IV collagen fibrils 3) 5% AD. Clinical picture; Alport: Microscopic hematuria; begins at about 5 to 7 years of age. Nephrotic proteinuria, HTN, ESRD late adolescence. Extrarenal manifestations; 1- sensorineural deafness, start gradually in childhood, handicap by 20 years of age. 2- Ocular abnormalities;lenticonus, Dot-and-fleck retinopathy; not interfere with vision. 3- esophageal leimyomas . Thin GBM= Benign familial hematuria represent 25% of patients with microscopic hematuria.

Nail-Patella Syndrome
AD. Clinical picture; appear at any age.
1) proteinuria to nephrotic syndrome. 2) nail dysplasia. (absent thumb nails) 3) Skeletal manifestations; absent patella, elbow dysplasia. 4) Eye manifestations; Heterochromia of the iris, cataracts.

XLR inborn error of glycosphingolipid metabolism. defective activity of the lysosomal enzyme a-galactosidase A accumulation of neutral glycosphingolipid in cellular lysosomes. endothelial damage contributes to much of the pathology in Fabry's disease. TTT= Enzyme replacement therapy. C/P; 1) Renal Manifestations; progressive proteinuria & decline of renal function. 2) Skin symptoms; Anhidrosis, Angiokeratoma. 3) Visual symptoms; cornea verticillata, 4) Neurological symptoms; PN, Hearing deficit . 6) Other symptoms: coarse facial features.

FABRY'S DISEASE

diabetic nephropathy
Incidence The risk for ESRD is 12 times as high in type 1 diabetes compared to type 2 diabetes. About 80% type 1 will progress to proteinuria and ESRD compared to only 20% of type 2. Stages; 1. Renal hypertrophy & hyperfiltration. 2. Normoalbuminuria, but detectable glom lesions. 3. Microalbuminuria (30-300 mg/24h= 20-200Ug/min= U alb/creat 0.03-0.3). 4. Overt proteinuria & azotemia. 5. ESRD.

Microalbuminuria 30-300 mg/24h = 20-200 Ug/min = U alb/creat 0.03-0.3. Affects 25-30% of diabetics. Progress in - 80% of type 1 & 20% of type 2 without ttt. Develop after 5-10 yrs of DM. Screening for Microalbuminuria is recommended in All type 2 diabetes at diagnosis. Type 1 diabetes 5 years after diagnosis, at puberty. Annually for all patient after.

Histopathology
LM; - Thick BM. - Mesangial expansion (diffuse, nodular=Kimmelstiel-Wilson lesion). - Aff & eff arteriolar hyalinosis. EM; -fibrin cap (esinophilic focal thickening of a peripheral cap loop)& - capsular drop (esinophilic focal thickening of bowmans capsule). IF; psuedolinear deposition of alb & Ig G along BM.

Preventive Strategies in Diabetic Nephropathy.

1. Tight glycemic control (A1C <7%). 2. Aggressive control of hypertension. Goal; DM <130/80 Diabetic nephropathy (>1g proteinuria/day) <125/75 3. Protein restriction. 4. Control of dyslipedemia. 5. Encourage smoking cessation. 6. Prevent sudden deterioration of kidney function.

7. Recent strategies in future.

Antihypertensives 1) ACEI; Acute rise of serum creatinine of up to 30-35%, stabilize after 2 months, may occur in proteinuric patients with serum creatinine >1.4mg/dl. greater increase of serum creatinine should raise the possibility of RAS. Albuminuria, serum creatinine and K should be checked monthly till 2-3 months. 2) DHP CCBs (nefedipine- amlodipine): may increase proteinuria and accerelate the progression of diabetic nephropathy. 3) NDHP CCBs (deltiazem, verapamil) may reduce proteinuria.

Lupus Nephritis
(WHO) classification & clinical presentation INormal;-------------------Mild proteinuria II Mesangial proliferation;---------------------asymptomatic hematuria or proteinuria III Focal proliferative (FPGN); <50% of all glomeruli----active generalized SLE -----------------------mild-to-moderate renal disease IV Diffuse proliferative (DPGN);-------Nephritic nephrotic + active generalized SLE VMembranous;-----------nephrotic syndrome, usually without manifestations of active SLE. VI Advanced sclerosis , >90% of glomeruli------------significant renal insufficiency Lab of lupus nephritis activity; +ve anti DNA,C3, C4 , +ve anti C1q(most specific), antinucleosome Ab , urine (hematuria, RBCs casts). Value of renal biopsy; poor correlation between C/P & histopath., associated pathology e.g. drug induced AIN, TMA.

LM; Wire-loop lesion = massive subendothelial immune deposits Hyaline thrombi = large intracapillary immune deposits Fibrinoid necrosis = intimal immune and fibrin deposits IF: full-house with IgG, IgA, IgM, C1q, C3, fibrin, and light chains. EM: All level dense deposits IImesangial; III and IV mesangial,subendothelial, Vsubepithelial Fingerprint subtructure immune deposits , Tubuloreticular inclusions, present also in HIV, most diagnostic.

Characteristic lesions

Therapy
Class I: no specific therapy. Class II: if proteinuria > 1 g/dprednisone (20-40 mg/d) for 1-3 months. Classes III and IV; Induction; pulse steroid +IV cyclophosphamide or MMF Maintenance; prednisone 1 mg/kg/d gradual tapering to 5-10 mg/d for 2 years + azathioprine or MMF. Class V: as 1ry membranous. Renal affection in rheumatoid arthritis; - Drug toxicity; NSAIDs AIN+nephrotic. - 2ry amyloidosis.

Gammopathies = diseases of globulins =immunoglobulin overproduction

Alb.= 3.3- 4.7 g/dl. 1 glob.=0.1-0.4 g/dl. 2 glob.=0.3-0.9 g/dl. 2 glob.=0.7-1.5 g/dl. glob.=0.5-1.4 g/dl.

Monoclonal Gammopathy Polyclonal Gammopathy Due to proliferation of many B cell clones e.g. CLD, Chr. Inflammation, infection.
= Plasma cell dyscrasias =immunoproliferative diseases
Due to proliferation of a single Clone of Ig-forming cells that produce homogenous excess of light, heavy chains or complete IG molecule. (M-protein, where the "M" stands for monoclonal).

MECHANISMS OF RENAL INJURY

I. Tubular precipitation; cast nephropathy (in MM) II. Deposition; Amyloidosis, LCDD III. Hyperviscosity; Waldenstrm macroglobulinemia & Myeloma dt Igs. IV. Glomerular reactions; MPGN, Pamidronate induced FSGS V. Tubular toxicity; ATN (NSAIDs, Iodinated contrast), Fanconi syndrome.

DIAGNOSTIC APPROACH TO RENAL DYSFUNCTION IN PLASMA CELL DYSCRASIA I. Serum protein electrophoresis - Monoclonal proteins will appear as a spike in the pattern - Sensitivity (500-2000 mg/L) - May not pick up small bands or bands outside of the gamma region II. Urine protein electrophoresis - Both serum and urine should be tested to increase detection to 95% III. Immunofixation - using Anti-serums to light chains. - More sensitive than electrophoresis (detection limits 150-500 mg/L) IV. Serum free light chains (FLC) assay Most sensitive (detection limit of 0.5 mg/L) Sensitivity is 99% when FLC is combined with serum and urine immunofixation V. Bone survey VI. Bone marrow biopsy VII. Abdominal pad of fat aspirate; 80% sensitive for AL amyloidosis VIII. Renal biopsy A. Should be performed on all cases if risk permits B. Only way to distinguish between various kidney diseases

Multiple Myeloma
= CAST NEPHROPATHY
Precipitating factors 1. Volume depletion 2. Hypercalcemia 3. NSAIDs 4. Intravenous contrast 5. Infections Pathogenesis A. Increased tubular concentration of light chains enhanced by decreased urine flow and furosemide. B. Binding and co-aggregation with Tamm- Horsfall proteintubular cast in the distal tubule then the proximal tubule C/P; Acute renal failure 10% to 15% present with ESRD > 75% have subnephrotic range proteinuria 1. Mainly Bence-Jones proteinuria 2. Often dipstick negative

V. Treatment
A. Restore intravascular volume B. Remove offending agents and nephrotoxic drugs 1. Hypercalcemia i. Volume repletion ii. Bisphosphonates in refractory cases. C. Reduce light chain levels 1. Chemotherapy i. Thalidomide plus dexamethasone, or ii. Bortezomib plus dexamethasone D. Stem cell transplantation +/- kidney transplant is an option in selected patients. VI. Management of ESRD A. Survival on dialysis is significantly decreased in patients with dysproteinemia who reached ESRD. 1. Median survival was 2 -4 years for LCDD, & AL amyloidosis and 1 year for multiple myeloma.

What are these homogenous deposits with light microscopy in this renal biopsy of a patient with long standing rheumatoid arthritis who has recently developed nephrotic syndrome

Slide no 12

AMYLOIDOSIS
TYPES OF AMYLOIDOSIS 1. AL amyloidosis 2. AA amyloidosis 3. Dialysis-related amyloidosis 4. Heritable amyloidoses e.g. heritable neuropathic and/or cardiomyopathic amyloidosis due to deposition of fibrils derived from transthyretin (also referred to as prealbumin). 5. Organ-specific amyloid Amyloid deposition can be isolated to a single organ, such as the skin, eye, heart, pancreas, or genitourinary tract, resulting in specific syndromes.

Renal Amyloidosis
1. Congo red +ve. Biopsy of involved liver or kidney is diagnostic 90% , abdominal fat pad aspirates are positive about 70%. SAP (serum amyloid P) scanning can identify the distribution of amyloidSensitivity = 90 % & ; the specificity is 93 %. AL amyloidosis, also called primary amyloidosis; 75% are of the lambda LC. 10% of these patients have overt myeloma. nephrotic syndrome is common, and about 20% of patients progress to dialysis. treatment ; melphalan+ dexamethazone, 4d courses/28 d for up to 9 courses. autologous hematopoietic stem cell transplantation . Thalidomide/dexamethazone. AA amyloidosis is sometimes called secondary amyloidosis nephrotic syndrome, 4060% of patients progress to dialysis. It is due to deposition of -pleated sheets of serum amyloid A protein, an acute phase reactant. 40% 2ry to rheumatoid arthritis, 10% have ankylosing spondylitis or psoriatic arthritis, FMF treatment of the primary disease, Colchicine in FMF, Eprodisate.

1. 2. 3.
2. -

Light Chain Deposition Disease

kappa light chains that do not form amyloid fibrils. Instead, they self-aggregate and form granular deposits along the glomerular capillary and mesangium, tubular basement membrane, nephrotic syndrome , 70% of patients progress to dialysis. not fibrillar and do not stain with Congo red, IF + anti-lightchain antibody. EM granular deposits. Treatment = Melphalan/prednisone for 2 years as MM. DD of nodular sclerosis; Diabetic glomerulosclerosis LCDD. Amyloidosis. Idiopathic.

Antiphospholipid antibody Syndrome

Def & pathogenesis; auto Ab to phospholipids on endothelial cells & LDL endothelial injury thrombotic microangiopathy. Diagnostic criteria; 1 clinical (thrombosis arterial or recurrent venous/ recurrent miscarriage before 34 wks of normal fetus) + 1 lab (anticardiolipin/ lupus anticoagulant) C/P; 1. livedo reticularis, thrombosis; CNS, CVS, adrenal insufficiency, lung, GIT, Kidney, ARF, TMA, HTN. 2. Catastrophic form => 3 organs simultaneously (Kid, lung, CVS). Lab; PTT, +ve anticardiolipin/ lupus anticoagulant, false +ve VDRL. Ttt; APA +ve without previous thrombosis no ttt or aspirin. APA +ve & previous clinical event long term warfarin, INR=2-3. APA +ve & pregnancy heparin.

scleroderma
Renal failure in scleroderma; - renal crises. - TMA - Membranous. Path; as TMA but affect arcuate & interlobular arteries, onion skin appearance, hypertrophy of JGA. Marker of Scl renal crises; anti-RNA polymerase III C/P; diffuse systemic scl + new onset severe HTN or RPRF. TTT; ACEI Prognosis; continue ACEI after dialysis as 50% may recover over 3-18 months.

Sickle cell; Glomerular; hematuria , FSGS. Tubular; DI , RTA , papillary necrosis. Renal cell carcinoma. Sarcoidosis; Ca stones, granulomas, TIN. Sjogren $; Membranous, RTA.

Cryglobulinemia
Cryglobulins are proteins ((Ig & Ag) that precipitate on cooling to 4o Precipitate in small cool Bvs in the peripheries complement activation Raynaulds, vasculitis. 33% is called essential cryo (uknown cause, discovered to be mostly related to HCV)

Type I Monoclonal

Type II Mixed Mono Ig M against poly Ig G (RF activity) HCV Plasma cell dyscrasia

Type III Mixed polyclonal - Autoimmune; SLE, hepatobiliary, GN. - Lymphoproliferative - Chronic infection

causes

Waldenstrom MM

C/P

Hyperviscosity, Raynaulds, cutaneous ulcers, Purpura, arthralgia, LN, HSM, peripheral neuropathy, GN; HTN, acute nephritic, nephrotic less common.

Gn; LM: Marked leukocytic infiltration, intraluminal deposits, vasculitis with fibrinoid necrosis, TI infiltration. IF; Ig M&G, C3. Lab; C4, C1q,+ve cryo, RF, HCV Ab. Poor prognostic factors; 1. Old age. 2. Recurrent purpura. 3. High s creat. 4. High cryo titre; Clinical and histologic activity does not always correlate directly with detection of circulating cryoglobulins. 5. Low C3 TTT; - steroids (pulse then 0.5 mg/kg for 6 months) + TTT of HCV. - If severe; add cyclophosphamide, - plasmapharesis& Rituximab.

 Hypocomplementemic GN; - Lupus nephritis - Post infectious. - MPGN - Cryoglobulinemia. HCV associated nephropathy; 1. MPGN +/- cryoglobulin 2. Membranous GN 3. FSGS 4. Prolif, TMA, fibrillary.

Thrombotic microangiopathies (TMA)

Def; group of disorders ccc by fibrin deposition in the lumen & wall of arterioles & glomerular cap. Path; LM; - intraluminal fibrin & plat. - double contour of cap wall. - fibrinoid necrosis of arterioles. EM; tactoids of fibrin(subendothelial), swollen endo. IF; no IC. Lab; platelets, hemolytic anemia, shistocytes. TTP more platelet. HUS: more RBCs & cortical necrosis.

Thrombotic thrombocytopenic purpura (TTP)

Pathogenesis;activity of VWF cleaving protein to < 5% large VWF platelet adhesion dt; - Familial ADAMTS13 mutation. - Acquired Ig e.g. with ticlopedine,peripartum,sepsis,malig. C/P; pentade; fever, hemolytic anemia, thrombocytopenia, CNS, mild renal . TTT; FFP, plasmapharesis,. NB: platelet transfusion & antiplatelet e.g. aspirin are contraindicated. FU by LDH level. Prognosis; mortality 90% if untreated, 90% survival if ttt.

Hemolytic Uremic Syndrome (HUS)

1. 2. 3. Pathogenesis; endothelial injury; By shiga toxins of Eoli O157 H7 (Diarreal form D+HUS). Complement mediated in familial form dt factor H. Complement mediated in the acquired form by a triggering factor e.g.pregnancy, malignancy, drugs. C/P; triad of hemolytic anenia, thrombocytopenia, severe renal failure. Ttt; supportive, recombinant factor H. Poor prognostic factors; old, pregnant, D-HUS, shigella, pneumococcal, HTN, cortical necrosis, marked leuckocytosis, anuria, persistent proteinuria.

 1. 2. 3. 4. 5. 6.

Uses of plasmapharesis in renal dis; Good pasture. ANCA +ve dis. Idiopathic cresentic Gn. Cryo. MM with hyperviscosity. TTP & HUS.

Tubulointerstitial diseases

Acute interstitial nephritis

1. 2. 3. 4. Causes; Drugs; antibiotics, diuretics, NSAIDs.PPI. Infections e.g.bact, viral as CMV, Hanta V, fungal. Immune dis; SLE, Sjogren, sarcoid, cryo, acute transplant rejection. Idiopathic. C/P; Fever, rash, arthralgias +/- flank pain, hematuria. Lab; Serum.., KFTs, & electrolytes. Urine.....RBCs , WBCs, White cell casts, eosinophiluria, Eosinophilia, tubular defects, proteinuria<1g. TTT; stoppage of offending agent high dose steroid for 2-3 wks for drug induced & systemic dis. not for infection.

Chronic interstitial nephritis

1. 2. 3. 4. Causes; Drugs; analgesics, lithium, heavy metals as lead, calcinurin inhibitors. Infections e.g. EBV. Immune dis; SLE, Sjogren, sarcoid, cryo, chronic transplant rejection. Obstructive uropathy.

CP.....> CKD,HTN, PCT defects, marked acidosis, hypo or hyperkalemia. Lead; renal, blue line in gum, gout, wrist & foot drop. diagnosis; lead mobilization test. TTT; chelation with EDTA or oral succimer.

Lithium; DI; ttt; stop it , give amiloride , thiazide , endomethacin,carbamazepine RTA, CIN, FSGS, ARF in acute intoxication, hypothyroidism, goiter, hypercalcemia.

Effect of NSAIDS
Vasomotor ARF. Acute interstitial nephritis + nephrotic S. Acute papillary necrosis. Nacl retension. K in low RAA as DM, ACEI. CKD; either NSAIDS- induced CKD.

NSAIDS- induced CKD

= age> 60 less

Does not occur with low dose aspirin

analgesic nephropathy Mixture; aspirin, paracetamol, caffeine ( 2-3) Kg). 40-50 Anemia out of proportion Diagnosed by non-contrast CT papillary necrosis & medullary calcification, small kidneys, irregular contour.

RENAL FANCONI SYNDROME

generalized dysfunction of the PCT. phosphate, glucose, amino acid, and bicarbonate wasting by the proximal tubule. C/P; in children is usually rickets and impaired growth. In adults, osteomalacia and osteoporosis. + polyuria, renal salt wasting, hypokalemia, acidosis, hypercalciuria, and LMW proteinuria.

 Age > 60yrs except sickle. Due to medullary blood flow. Causes; DM UT obstruction. Analgesic nephropathy. Sickle cell anemia. Graft rejection Pyelonephritis, TB. Hyperviscosity syndromes. C/P; hematuria , necroturia , loin pain, UTI, sepsis, renal failure. Diagnosis; IVP (best). signs;calyceal irregularities, sinus tract, ring sign, clubbing, filling defects. prevention; ACEI are protective. TTT; control B sugar, avoid analgesics & drugs that Bl flow as thiazides, BB, fluids,

Papillary necrosis

Vesicoureteric reflux
Not inherited. Most common cause of ESRD in children. Child with UTI 30% VUR. NB; Most common inherited cause of ESRD ADPKD. Most common inherited cause of ESRD in childrennephronophthisis (as medullary cystic dis). Reflux nephropathy=VUR + CIN. Grades; I ureter II ureter & pelvis ( without dilatation). III pelvic dilatation, preserved forniceal angles. IV blunting of forniceal angles. V clubbing of forniceal angles.

 Diagnosis; - early micturating cystography, dynamic renal scan. - late U/S, DMSA scan. Screening for VUR in: : 1st attack of UTI at any age. : 2nd attack or- 1st with family history, - abn. Voiding, - HTN, - poor growth, TTT; Grade I nothing. Grade II, III till puberty antibiotics TMP-SMX or nitrofurantoin, cephalexin. Grade IV, V Long-term antibiotics or surgery. NB: Surgical correction of VUR in children have failed to show significant benefit in terms of renal function & progressive scarring. Surgical correction is reserved for the child who, in a 2- to 4-year period, appears to be not responding to medical therapy.

Cystic diseases of the kidneys

1. 2. Hereditary; ADPKD. ARPKD. Tuberous sclerosis Von Hippel-Lindau disease (VHL) Juvenile nephronophthisis and medullary cystic disease. Acquired renal cysts; Medullary Sponge Kidney. acquired cystic disease. Simple cysts.

cystic Kidney Disease

Inherited Cystic Kidney Disease ADPKD Nephronophthisis Mode of Inheritance AD AR Renal Abnormalities Cortical and medullary cysts Small fibrotic kidneys; medullary cysts Small fibrotic kidneys; medullary cysts Renal cysts; angiomyolipomas; Extra-Renal Abnormalities Cerebral aneurysms; liver cysts, othera Retinitis pigmentosa

Medullary cystic kidney disease Tuberous sclerosis

AD

None

AD

Adenoma sebaceum; CNS hamartomas

Von Hippel-Lindau disease

AD

Renal cysts; renal cell carcinoma

Retinal angiomas; CNS hemangioblastomas; pheochromocytomas

Adult Polycystic disease

1. Commonest inherited kidney disease. Accounts for 5-10% of (ESRD). Clinical Picture Renal disease; Abdominal pain , hematuria, Palpable kidneys, Recurrent UTI,stones, Hypertension, Renal Failure . 2. Extra renal disease; Cerebral Aneurysm (Berrys) (5-10%), Hepatic, Pancreatic cysts, Mitral Valve Prolapse (26%),diverticulosis. Diagnostic radiological criteria If +ve Family history < 30 years ----- 2 cysts in at least one kidneys. 30 - 59 years ----- 2 cysts in each kidney. > 60 ---4 cysts in each kidney. If -ve Family history 5 cysts in each kidney. TTT; 1. ACEI, ARBs 2. If Hge; analgesics, rest, hydration. 3. If infected; bl culture not urine,sutrim, cipro, vanco not ceph nor

APKD

Tuberous sclerosis
AD, hamartin (tumor suppressor)multiple hamartomas.

Clinical Picture;
CNS epilepsy in 80%, Mental retardation. SkinFacial adenoma sebaceum, Shagreen patches (lower back), Ash leaf (Hypomelanotic macules). Periungual fibromas. Renal (60%) cysts, Angiomyolipomas. Retinal hamartoma (50%), is almost always asymptomatic. Liver ( 40% ), angiomyolipomas and cysts. Heart (rhabdomyoma). Lung (lymphangiomyomatosis; affects females)

Acquired renal cysts

Medullary Sponge Kidney - dilatation of collecting ducts, Benign course. Calcify nephrocalcinosis, Nephrolithiasis and UTI. Defective concentrating ability & RTA. Diagnosed by IVPradial, linear striations in the papillae or cystic collections of contrast . Dialysis Cysts= acquired cystic disease. the size of the kidneys is usually not markedly increased, Precancerous. Simple cysts - Fluid filled, may enlarge to 10 cm. - Single or multiple. - Common 2% of people< 50y, up to 20% > 70yrs.

Acquired cystic disease of the kidney

Acquired cystic disease of the kidney

Vascular renal diseases

Renovascular HTN
Clues;
- abrupt onset, accelerated HTN. - recurrent flash pulmonary edema. - Deterioration in renal function with BP reduction and/or ACE inhibitor therapy. - Generalized atherosclerosis obliterans. - asymmetrical kidneys.

Causes;
- RAS (narrowing > 50%) - vasculitis - TMA.

Atherosclerotic renal artery disease (ASO-RAD)

5th to 7th decades of life. 70-80% ostial stenosis. Tend to progress, renal impairement. TTT; anti HTN, lipid lowering,antiplat. interfere if; > 60% stenosis. progressiveKFTs evidence of salvageability; - normal Kid size - good function in renal scan - RI<80 TTT percutaneous angioplasty +stent . if failed surgical revascularization

114

Classification of renal artery stenosis:

1. Atherosclerotic renal artery disease (60 - 80%) 2. Fibrous dysplasias (20 - 40%).

FMD
Female, 30-50 yrs. Slow progression. Renal functions preserved. 1% of HTN. Most frequent is medial dysplasia with multiple contiguous stenosis string of beads. TTT; ACEI, percutaneous angioplasty (curable, low restenosis), if failed surgical revascularization

Hypertensive Nephrosclerosis
27% of ESRD patients. risk factors for progression to ESRD include age, sex, race, smoking, hypercholesterolemia, duration of hypertension, and preexisting renal injury. Kidney biopsies (not needed); arteriolosclerosis, chronic nephrosclerosis, and interstitial fibrosis in the absence of immune deposits . TTT; Treating hypertension <130/80 mmHg if there is preexisting diabetes or kidney disease, most patients begin therapy with two drugs, classically a thiazide diuretic and an ACE inhibitor.

Renal vein thrombosis

Etiology; History of nephrotic syndrome or pulmonary embolism. C/P; Flank pain. Urine analysis; Mild proteinuria Occasional hematuria. Renal venogram or MR venogram are diagnostic.

Atheroembolic disease
Def; separation of cholesterol crystals from atheromatous plaques to small renal arteries. Etiology; Vascular disease; classically occurs within days
weeks of manipulation of the aorta or other large vessels as coronary angio, or in the setting of anticoagulation.

Clinical picture; Retinal plaques, palpable purpura, livedo

reticularis, slow deterioration of renal function. Lab; Eosinophilia, Hypocomplementemia, Eosinophiluria Diagnosis; Skin or renal biopsy ccc clefts, concentric intimal fibrosis, FSGS. TTT; stop anticoagulation, low dose steroids.

Urinary tracts

Urinary Tract Infection

The infecting organism E coli =80-95% Staph. Sapro. = 5-10% Enterococci (Strept. fecalis) =5-14% Others; proteus = 2-3%,Klebsiella = 2-3%, Pseudomonas, candida esp in complicated cases.
Uncomplicated UTI= healthy young woman. 1. Uncomplicated cystitis; - C/P; dysuria, frequency, suprapubic pain. - diagnosis; history, urine analysis pus cells>4/HPF. - TTT; 3 daysTMP/SMX or Quinolones or 5d Nitrofurantoin. - if recurrent long term small dose postcoital or 3 times/wks at bed time.

2. Uncomplicated pyelonephritis; - C/P; fever, loin pain. - diagnosis; urine culture; bact count >104 - TTT; TMP/SMX or Quinolones (IV if vomiting) till culture sensitivity for a total of 14 days.

 Complicated UTI;
- In structural or functional abn e.g. anatomic abnormality, Instrumentation, Medical condition; as Pregnant, Diabetic CKD, transplant,Nosocomial,Childhood UTI, symp.> 7d, Drugs; antibiotics, immunosup. - Elderly, men & children. diagnosis; bact count >105. TTT; 7 days for lower & 14 days for upper UTI with broader spectrum Ab covering pseudomonas e.g. Piperazin/tazobactam, Cefepime, Imipenem, Meronem,. if recurrentlong term suppressive therapy ie full dose then dose when culture ve.

Catheter-Associated UTI
Asymptomatic patient no therapy is indicated. (as relapse is very common). In symptomatic patient antibiotics is based on the Gram's stain of urine or the antimicrobial sensitivity patterns. Prophylactic antimicrobial therapy In case the time of catheterization is clearly limited (e.g., in gynecologic , vascular surgery, kidney transplantation).

UTI in Men
In men > 50 years with UTI, - Intensive therapy for at least 4 to 6 weeks up to 12 weeks is recommended due to deep tissue invasion of the prostate & the kidneys even in the absence of overt signs of infection at these sites. Treat Relapse (1) long-term antimicrobial suppression (2) surgical removal of the infected prostate.

Asymptomatic bacteriuria in Pregnancy

Screening for asymptomatic bacteriuria by urine culture at the first prenatal visit (12-16 wks pregnancy) is mandatory (for fear of pyelonephritis that develop by the end of the second trimester & so may lead to premature delivery).
If +ve repeat to confirm then treat with 5- 7 days of nitrofurantoin (100 mg twice daily) , amoxacillin (500 mg PO three times daily ) cephalexin (500mg twice daily). FU culture 1 week after and then monthly until the completion of the pregnancy.

 1. 2.

Candida AlbicansFluconazole, itraconazole or 5 flurocytosine. Treat if: symptomatic, Asymptomatic only if neutropenia, or urinary tract manipulation or repeated culture counts > 10.000. otherwise rapid recurrence is common, selection of resistant Candida, and clinical outcomes do not appear to be improved . Regimens: 1. Catheter-associated candidal UTI, removal of the preceding catheter, insertion of a three-way catheter, and infusion of an amphotericin rinse for a period of 3 to 5 days . 2. Without catheter, fluconazole, 200 mg/day for 10 to 14 days, (insertion of a catheter for an amphotericin rinse carry risk of bacteriuria). Success is increased if such contributing factors as hyperglycemia, corticosteroid use, and antibacterial therapy can be eliminated.

Fungal Infection of the Urinary Tract

Etiology of Urolithiasis
Anatomical causes - ureteropelvic junction (UPJ) obstruction, - Horseshoe or ectopic kidney - vesicoureteral reflux, - calyceal diverticula - medullary sponge kidney Metabolic causes - low urinary volume, - hypercalcuria (25%40%), - hyperoxaluria (10%50%), - hyperuricosuria(8%30%) and - hypocitraturia (5%30%)

Major Causes of Renal Stones

Stone Type and Causes
Calcium stones 85% ,

Etiology

Diagnosis

Treatment

Alkali supplements + Hereditary(?) Normocalcemia, unexplained hypercalciuria ( > 300 mg / 24 hrs ). Unexplained hypercalcemia Hyperchloremic acidosis, minimum urine pH >5.5 Urine oxalate >45 mg per 24 h diet; thiazide

Idiopathic hypercalciuria 50% 1ry hyperPTH Distal RTA hyperoxaluria

Neoplasia Hereditary High oxalate or low calcium diet Bowel surgery Hereditary

Surgery Alkali replacement Low oxalate diet Cholestyramine pyridoxine

Hypocitraturia

Hereditary (?), diet

Urine citrate <320 mg per 24 h

Alkali supplements

%Occurrence

Etiology

Diagnosis

Treatment

Uric acid stones 5-10%

Hyperuricosuria

50% Gout 50 % Idiopathic

Dehydration Cystine stones 1% Struvite stones 5-10%

Hereditary Intestinal, habit

Clinical diagnosis Uric acid stones, Urine uric acid >750 mg /d (women), >800 mg /d (men) Stone type; elevated cystine excretion Stone type

Alkali and allopurinol if urine uric acid >1000 mg/d

Hereditary Infection

Massive fluids, alkali , D-penicillamine Antimicrobial agents Acetohydroxamic acid judicious surgery

Dietary modification Increase fluid intake to maintain urine output of 2-3 l/day: Decrease intake of animal protein Restrict salt intake Normal calcium intake. Decrease dietary oxalate;

RENAL STONES
Calcium oxalate stones are the commonest kind of stones. Calcium phosphate stones are the second commonest and associated with 1ry hyperpara, d RTA, CAI (alkaline urine). Uric acid stones (5% of all stones) are associated with high purine metabolism, chronic diarrhoea, gout. cystine stones associated with amino aciduria; a disorder of proximal tubular cells. (COAL cystine, ornithine, arginine, lysine) . Proteus splits urea into ammonia, causing alkaline urine struvite stones (magnesium ammonium phosphate). Radiopaque stones are: Calcium oxalate, calcium phosphate, triple phosphate, cystine stones. Radiolucent stones are: Uric acid, xanthine stones.

comprehensive metabolic evaluation serum calcium, bicarbonate, creatinine, chloride, potassium, magnesium, phosphate, and uric acid. 24 hour urine collections for: volume, pH, calcium, oxalate, citrate, uric acid, phosphate, sodium, potassium, and creatinine. Na nitroprusside test & 24 hour measurement of cystine Intact PTH and 1,25 dihydroxycholecalcifirol in hypercalcaemic patients. Indicated for; 1. Patients with multiple stones at first presentation, 2. Patients with family history of urinary stones. 3. Patients with recurrent urinary stone.
Noncontrast helical Computed Tomography (CT) 91% sensitive and 98% specific in detecting urolithiasis

Beverage type Coffee and tea Alcohol Milk Lemon juice Grapefruit juice Cranberry juice Carbonated beverages Cola

risk Decreased Decreased Decreased Decreased Increased Increased Increased Increased

Promotors & Inhibitors of stone formation

Dietary factor Promotors Oxalate Sodium Animal protein Increased urinary oxalate excretion Increased urinary calcium excretion Increased urinary calcium and uric acid excretion; reduced urinary citrate excretion Proposed mechanism(s)

Vitamin C
Inhibitors Dietary calcium Potassium Phytate Magnesium Urinary citrate Vitamin B6

Increased oxalate generation and excretion

Binding of dietary oxalate in gut Increased urinary citrate excretion; reduced urinary calcium excretion Inhibition of calcium oxalate crystal formation Reduced dietary oxalate absorption; inhibition of calcium oxalate crystal formation oppose crystal formation by thermodynamic and kinetic mechanisms Vitamin B6 deficiency may increase oxalate production and oxaluria

Hyperoxaluria
urinary excretion of oxalate in excess of 45 mg/day. Primary (Inherited) Hyperoxaluria. Rare AR , excessive oxalate production and systemic deposition of calcium oxalate tissue damage e.g. heart, bone, retina, kidneys Nephrocalcinosis. Secondary (Enteric) Hyperoxaluria. - Reduced availability of free calcium to bind intestinal oxalate in malabs. - The colon absorbs unbound oxalate. - increased colonic permeability in IBD. - Contributing factors include a low urinary citrate concentration, decreased urine volumes, and a low urinary pH, all due to diarrhea and consequent loss of fluid and bicarbonate in the stool. NB; Renal stones are primarily composed of calcium oxalate when the ileum is involved (e.g., ileocolonic Crohns disease), and uric acid when patients have copious diarrhea or small bowel ostomies.

Retroperitoneal fibrosis
1. 2. 3. Definition; ureter embedded in dense fibrous tissue Causes; Idiopathic (, 40th-50th) Trauma, surgery, radiation. Inflammation; infection, granuloma, autoimmune (sclerosing cholangitis) Neoplastic; lymphoma, Cx, bladder. Drugs; methysergide, bromocriptine, ergotametrine ,MD, hydralazine, BB. C/P; insidious onset of dull aching pain. IVP & U/Smedial indrawing of ureter at junction of middle & lower part. CT; periaortic mass. ESR very high. TTT; surgical releave of ureter, steroid for idiopathic type.

4. 5.

Acute Renal Failure

Def; Acute renal failure (ARF) is characterized by a rapid decline in glomerular
filtration rate (GFR) over hours to days. 1. Prerenal (60-70%) - ESF volume; renal loss e.g,diuretics, extrarenal e.g. diarrhea, burns - effective bl volume; COP , VD , oedematous states. - intrarenal VC; cyclosporin, NSAIDs, ACEI, HRS. 2. Intrinsic renal (25-40%); - ATN; ischemic, toxic e.g. G-ve sepsis/ Endogenous as rhabdomyolysis, hemolysis, cast neph, tumour lysis / exogenous toxins; aminoglycosides, amphotericin, cisplatinum,cyclosporin. - tubular obstruction; Endogenous: myeloma proteins, uric acid (tumor lysis syndrome). Exogenous: acyclovir, gancyclovir, methotrexate, indinavir, ethylene glycol. - AIN. - vascular; TMA e.g. DIC, malignant hypertension, preeclampsia. - glomerular; acute nephritis. 3. Postrenal ARF (Obstruction) I. Ureteric (bilateral, or unilateral in the case of one kidney): calculi, blood clots, sloughed papillae, cancer, external compression (e.g., retroperitoneal fibrosis) II. Bladder neck: neurogenic bladder, prostatic hypertrophy, calculi, blood clots. III. Urethra: stricture or congenital valves

 Prerenal ARF; - High BUN/CR ratio>20. - FENa < 1 % -UNa <10 mmol/L - high urine osmolarity > 500 mosm/l. - SG >1.018. Renal (Acute tubular necrosis); - Muddy brown granular or tubular epithelial cell casts - FENa > 1 % - UNa > 20 mmol/L - low urine osmolarity < 500 mosm/l. - SG <1.015

Diagnosis Rhabdomyolysis (Myoglobinuria)

cause Physical Metabolic & elect. Drugs. infections

serum

urine

ttt Fluid therapy forced alkaline diuresis with HCO3, mannitol in dextrose

Increased U/A positive for myoglobin, heme but no CPK,creatinine, RBCs P, K, uric acid, high AG MA, Ca. BUN/creat<10 Pink plasma, Increased LDH

Hemolysis: recent blood transfusion, G6PD, PNH, cold Ab Tumor lysis

Fever, other evidence of transfusion reaction recent chemotherapy

Pink, hemeAs Myoglob. positive urine without hematuria, hemosiderinuria Urate crystals urine uric acid/u creat>1 alkalinization of urine, allopurinol, uricase, fuboxostat

Hyperuricemia, increased LDH

Hepatorenal syndrome
It is a functional impairement in kid functions 2ry to intrarenal VC in LC with S. creat > 1.5 mg/dl or GFR < 40 ml/min in the absence of any other cause of kid dysfunction. Major criteria for diagnosis; LCF with portal HTN. S creat > 1.5 mg/dl or GFR < 40 ml/min No improvement after stopping diuretics & fluid chalenge of 1.5 L. Absence of shock, infection, nephrotoxins. Proteinuria <0.5 gm/dl, US normal, no obst or parenchymal change. Minor criteria; S Na < 130 meq/l Urine Na< 10 meq/l Urine/P osm>1 Urine volume<1 l.

1. 2. 3.
4. 5.

1. 2. 3. 4.

Contrast nephropathy
Non oliguric ATN acute rise of serum creatinine 24-48 hrs after administration of IV contrast, peak = 3-5 days, baseline = 7-10 days. Risk factors; DM, CKD, MM, ACEI, NSAIDS, prerenal failure, high dose. Pathophysiology; VC & tubular toxicity. Prevention; 1. Use of low osmolality, non ionic contrast agent e.g. gadopentate dimeglumine (ultravest). 2. Least dose. 3. IV infusion of NS 1-2 hrs before to 24 hrs after at a rate of 1 ml/kg/hr. 4. Acetylcysteine 600 mg sachet/12 hr 2 days before. 5. +/- theo 2 ds before, nefidipine 10 mg subluigual before. 6. # mannitol, frusemide, dopamine, ANP. TTT; fluid chart, electrolytes, HD. NB; Gadolinium in MRInephrogenic systemic fibrosis.

Chronic Kidney Disease

Classification of Chronic Kidney Disease (CKD) Stage 1 GFR, mL/min per 1.73 m2 > 90b

2
3 4 5

8960
5930 2915 < 15

bWith demonstrated kidney damage (e.g., persistent proteinuria, abnormal urine sediment, abnormal blood and urine chemistry, abnormal imaging studies). Cockcroft-Gault equation; GFR e= (140-age) x BW/s. creat x 72 X 0.85 for women

Clinical and Laboratory Manifestations of CKD and Uremia

Fluid and electrolyte disturbances Volume expansion Na, K,P Endocrine-metabolic disturbances Secondary PTH Adynamic bone dis. Vitamin Ddeficient osteomalacia Carbohydrate resistance Hyperuricemia Hypertriglyceridemia. Decreased HDL Protein-energy malnutrition Impaired growth Infertility and sexual dysfunction Amenorrhea Neuromuscular disturbances Fatigue, Sleep disorders Headache, Impaired mentation Lethargy, Asterixis Muscular irritability PN, Myoclonus, Myopathy Restless legs syndrome Seizures, Coma Muscle cramps Dialysis disequilibrium Cardiovascular and pulmonary disturbances Arterial hypertension CHF Pericarditis,Hypertrophic or dilated cardiomyopathy , Accelerated atherosclerosis Hypotension and arrhythmias Vascular calcification( Dermatologic disturbances Pallor, Hyperpigmentation Pruritus Ecchymoses Nephrogenic fibrosing dermopathy ,Uremic frost Gastrointestinal disturbances Anorexia, Nausea and vomiting, Peptic ulcer Gastrointestinal bleeding Idiopathic ascites.

Hematologic and immunologic disturbances Anemia Bleeding diathesis Increased susceptibility to infection Leukopenia Thromboathenia

Treatment * Slowing the Progression of CKD

1. 2. Protein Restriction, between 0.60 and 0.75 g/kg per day. Reducing Intraglomerular Hypertension and Proteinuria; ACE inhibitors and ARBs, target blood pressure in proteinuric CKD patients=125/75 mmHg. Slowing Progression of Diabetic Renal Disease; hemoglobin A1C should be < 7%. Managing Other Complications of Chronic Kidney Disease. Medication Dose Adjustment. Preparation for Renal Replacement Therapy.

3.
4.

5. 6.

* Renal replacement therapy.

Dialysis in the Treatment of Renal Failure

Hemodialysis

Hemodialysis relies on the principles of solute diffusion across a semipermeable membrane. Movement of metabolic waste products takes place down a concentration gradient from the circulation into the dialysate.
Hypotension. Muscle cramps. Anaphylactoid reactions to the dialyzer. Disequilibrium S.

Complications during Hemodialysis;

1. 2. 3. 4.

Peritoneal Dialysis In peritoneal dialysis, 1.53 L of a dextrosecontaining solution is infused into the peritoneal cavity and allowed to dwell for a set period of time, usually 24 h. As with hemodialysis, toxic materials are removed through a combination of ultrafiltration and down a concentration gradient. The major complications of peritoneal dialysis are peritonitis, catheter-associated infections, weight gain and other metabolic disturbances, and residual uremia.

Anemia of CKD
1. 2. 3. 4. Develops when the GFR < 60 mL/min, symptomatic only when GFR<30 ml/min due to increase 2,3DPG & LVH. normocytic and normochromic. due to; reduced renal erythropoietin production (reduction in functioning renal mass) and, shortened red cell survival (60-90d vs. 120d). Hemolysis, bl loss during HD. Bleeding tendency & Fe deficiency. Anemia may be a risk factor for progression of CKD.

 TTT
1. Correct Fe deficiency
if ferritin <200 ng/ml & TSAT<20%. Target ferritin 200-500 ng/ml & TSAT=20- 50%. For predialysis oral 200mg elemental Fe/d or IV 200mg/1-3 months. for HDIVI, 100mg for 10 sessions then /wk. Side effects; free Fe reaction; N,V,BP, back pain. Anaphylaxis (Fe dextran due to anti-dextran Ab). Contraindications; Active inflammation. Fe overload.

1. 2. 1. 2.

2) Erythropoietin

1. 2. 3. 4.

When Hb of < 11 g/dL . Target Hb= 11 to 12 g/dL , NOT above 13 g/dL (adverse CVS effects, increase risk for hypertension ) . EPO , , Darbipoitin. Dose= 80-120 U/Kg/wk SC, dose by 30-50% iv. SC rather than IV ; stable level, more biologically active but PRCA with EPO. dose by 25% when target reached. Benefit; regression of left ventricular hypertrophy. aerobic capacity, cognitive and sexual function. Side effects Hypertension Headache PRCA; due to neutralizing anti-erythropoietin antibodies

 Causes of EPO resistance;

1. Iron deficiency (most common ) 2. Bone disease due to 2ry hyperparathyroidism. 3. Occult malignancy 4. vitamin B12 and folic acid deficiency. 5. Multiple myeloma/myelofibrosis/myelodysplastic syndrome. 6. Chronic inflammation. 7. Aluminum toxicity. 8. Hemoglobinopathies. 9. ACEI or ARBs. 10.pure red cell aplasia with neutralizing anti-erythropoietin antibodies esp. with SC EPO . 11.HIV infection.

Renal Osteodystrophy
A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: - Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism - Abnormalities in bone turnover, mineralization, volume, linear growth, or strength -Vascular or other soft tissue calcification

Renal Osteodystrophy
A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: - Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism - Abnormalities in bone turnover, mineralization, volume, linear growth, or strength -Vascular or other soft tissue calcification Pathogenesis; PO4 Vit D Ca Bone PTH Normal pulsatile action+ osteoblast Continuous high downregulate osteoblast receptors unopposed osteoclastCa/P efflux

Classification; 1. High turnover disease (2 ry PTH > 300 pg/ml or osteitis fibrosa). 2. low turnover (adynamic) bone disease ( PTH<150 pg/ml ) due to Ca load= overtreated. 3. Osteomalacia ( defective mineralization) due to Alm. Toxicity, Vit D, metabolic acidosis, P. 4. Mixed uremic osteodystrophy; 2 ry PTH + Osteomalacia

 1. 2. 1.

2. 3. 4. 5. 6.

C/P; Bony aches, reccurent pathological fractures. Soft tissue calcifications; vascular, valvular, skin. calcifications in atherosclerotic plaques, arteriosclerosis, calciphylaxis. Diagnosis; Intact PTH= full length PTH (1-84)(active) + PTH fragment (7-84)( inactive accumulate in RF). Bone specific ALK P (osteoblastic act). Bone biopsy. X rays. DEXA. Desferoxamine test for Alm tox.

C 1

PTH

84

TTT
1. Best= sevelamer + Vit D analogue. P; - dietary restriction - Ca based P binders; Ca carbonate, acetate. - if Ca AL OH, sevelamer, lanthanum carbonate. PTH; - Vit D (calcitriol). - Vit D analogues (1 , paricalcitol) - calcimimetics (cinacalcet= CaSR agonist) - PTH dectomy if; PTH > 800 + Ca or P despite medical TTT. calciphylaxis severe sympt. Transplantation.

2.

3.

This is a patient with end stage renal disease, with severe uncontrolled hyperparathyroidism. What is the skin lesion

Slide no 9

Transplantation
Tissue Typing; 1. ABO(O) blood groups 2. human leukocyte antigen (HLA) class I (A, B, C) or class II (DR) antigens 3. Punnel of reactive antibodies (PRA) 4. cross-match of recipient serum with donor T lymphocytes

Hyperacute

Accelerated acute

Acute

Chronic

onset

immediate

5 days
cellular & humoral memory T cells Interstitial tissue mononuclear & neutrophyl infiltration & vasculitis

5 d-4 m
cellular T cytotoxic Interstitial tissue mononuclear infiltration

> 4m
cellular & humoral T helper & B lymphocytes Chronic interstitial nephritis & fibrosis

Mechanism Humoral

Effector

preformed Ab

Pathology Intravascular thrombosis

Immunosuppressive Treatment
1. Induction therapy with Antibodies to Lymphocytes; Depleting Ab e.g. - ATGAM, OKT3 - Thymoglobulin is the most common agent currently in use. - Alemtuzumab non- Depleting Ab e.g. - anti CD25 (IL2 receptors); Basiliximab & Daclizumab. - Belatacept (costimulatory pathway blockade) 2. Maintenance Immunosuppressive Drugs

Agent
Glucocorticoids

Mechanisms
Binds heat shock proteins. Blocks transcription of IL-1,-2,-3,6, TNF and IFN calcineurin --block IL-2 production; however, stimulates TGF production

Side Effects
Hypertension, glucose intolerance, dyslipidemia, osteoporosis

Cyclosporine CsA

Nephrotoxicity, HTN, dyslipidemia, glucose intolerance, hirsutism/ hyperplasia of gums Similar to CsA, but hirsutism/hyperplasia of gums unusual, and diabetes more likely

Tacrolimus (FK506)

Azathioprine Mycophenolate mofetil (MMF) Sirolimus

inhibit purine synthesis Inhibits purine synthesis

Marrow suppression (WBC > RBC > platelets) Diarrhea/cramps; dose-related liver and marrow suppression is uncommon Hyperlipidemia, thrombocytopenia

blocks p70 S6 kinase in the IL-2 receptor pathway for proliferation

The Most Common Opportunistic Infections in the Renal Transplant Recipient

Peritransplant (<1 month) Wound infections Herpes virus Oral candidiasis Urinary tract infection
Early (16 months) Pneumocystis carinii Cytomegalovirus Legionella Listeria Hepatitis B Hepatitis C

Late (>6 months) Aspergillus Nocardia BK virus (polyoma) Herpes zoster Hepatitis B Hepatitis C

BK virus BK virus nephropathy & ureteral stenosis. Urothelial carcinoma,vasculopathy. Biopsy; patchy interstitial infiltration, IF; Ab to simian v. 40. Urine cytology +ve for decoy cells(tubular cells appear malignant due to viral inclusions. PCR. TTT; reduce IS, leflunamide, cidofovir.

Malignancy The incidence of tumors in patients on immunosuppressive therapy is 56%, or approximately 100 times greater than that in the general population of the same age range. The most common lesions are cancer of the skin and lips and carcinoma in situ of the cervix, as well as lymphomas such as non-Hodgkin's lymphoma. The risks are increased in proportion to the total immunosuppressive load administered and time elapsed since transplantation. Surveillance for skin and cervical cancers is necessary.

Slide no 2 This skin lesion appeared 2 months after a successful renal transplant What is the most likely diagnosis

Rate of relapse & graft loss

Glomerular disease recurrence FSGS Membranous 15% 10% graft loss 50% 50%

Ig A
MPGN Alport

50%
50%

15%
anti-GBM

Pregnancy related kidney diseases

ARF in pregnancy; 1st trimester; hyperemesis, septic abortion. 2nd trimester; TTP (any time). 3rd trimester; acute fatty liver, HELLP, post renal dt enlarged fibroid, stones, Gravid uterus, Polyhydramnios. Post partum; HUS, bil cortical necrosis.

TTP
timing 2nd, 3rd trimester

HELLP
3rd trimester

Acute fatty liver

3rd trimester (more common)

HUS
postpartum

Cortical necosis
postpartum Hge e.g. abruptio placentae Oliguria Hematuria Flank pain

C/p

Fever neuro

-Mild renal failure -Proteinuria -HTN

-ANV abd pain -Hepatic encephalopathy - hypoglycemia -Jaundice - DIC -Severe renal failure -liver enz -PT, PTT, plat -fibrinogen -congugated bil - hypoglycemia

-Severe renal failure - Poor renal prognosis

Lab

-plat, Hb -uncong. bilirubin -shistocytes

-liver enz -uric acid Hypocalcuria -PT, PTT, plat termination

Hypo or hyper echoic areas in US

ttt

plasmapharesis

termination

Supportive dialysis

dialysis

Hypertensive disorders in pregnancy;

1.Pre-eclampsia (27%); de novo, after 20th week gestation, resolve within 3 months + proteinuria. 2.Chronic HTN (23%); before pregnancy, before 20th week gestation, does not resolve post partum (essential 19% or 2ry 4%) 3.Pre-eclampsia superimposed upon underlying HTN(7%) 4.Gestational HTN (43%); mild, de novo, after 20th week gestation, resolve within 3 months without maternal organ dysfunction.

NB; preeclampsiaafter 20 wks, liver enzymes, normal Complement. Lupus activity complement.