Kidney diseases Dr Manoj Radhakrishnan Addl Professor Dept

Kidney diseases Dr. Manoj Radhakrishnan Addl Professor Dept. Of Pathology

The main clinical renal syndromes �Acute Nephritic syndrome �Nephrotic syndrome �Asymptomatic hematuria, proteinuria, or both �Acute renal failure �Chronic renal failure �Renal tubular defects �Urinary infections �Obstructive uropathy �Urinary stones �tumors

Principal laboratory findings in Uremia(endstage kidney disease) �Azotemia(incrsd. BUN blood urea nitrogen, & serum creatinine) �Electrolyte abnormalities(retention of sodium, potassium and phosphate with secondary changes in calcium) �Acidosis �Anemia �Prolonged bleeding time

Acute nephritic syndrome �Typically presents 1 -2 weeks after an upper respiratory tract infection caused by streptococci Ø Oliguria : due to reduced GFR Ø Hematuria : due to damaged GBM, brownish- red urine, RBCs in urine sediment Ø Protienuria : increased permeability of GBM, maybe mild or severe Ø Generalized edema: “ puffy eyes” due to hypo albuminemia Ø Hypertension : reduced GFR leads to secretion of renin Ø Low complement levels in blood: immune complexes bind the complement Ø Azotemia : high bld urea & serum creatinine

Nephrotic syndrome �Protienuria : massive > 3. 5 g/day �There is hypoalbuminemia �Generalized edema : due to reduced oncotic pressure (hypoalbuminemia) �Hyperlipidemia(increased LDL, lipid casts in urine �Affected patients are prone to infection & thrombotic events because of increased urinary loss of serum protiens

Derangements of urine volume �Anuria : reduced urine output (< 100 ml urine per day ) reflecting renal injury �Oliguria : reduced urine output below 400 ml / day sign of renal failure �Polyuria: increased volume of urine ( > 3 L of urine per day) may result from excessive fluid intake, osmotic diuresis( eg Diabetes insipidus) or impaired tubular concentration (eg tubular necrosis)

Features of Acute renal failure �Is characterised most often b reversible detrioration of renal function Ø Oliguria Ø Azotemia ( increased Blood Urea, Serum Creatinine) Ø Electrolyte disturbances �Most patients recover without dialysis

Chronic renal failure �Develops insidiously in stages Ø Diminished renal reserve : develop high urea, creatinine levels during inter-current illness Ø Renal insufficiency : GFR ( 20% - 50% of normal)azotemia anemia, polyuria Ø Renal failure : (<20% of normal GFR) & edema metabolic acidosis hypocalcemia, and multi-sstem signs of uremia Ø End-stage renal failure : <5% GFR , clinical signs of uremia

Features of urinary tract Infection �Charcterised by bacteriuria & pyuria �>100, 000 bacteria/ml of cultured urine �> 10 wbcs /HPF in urine sample �Leucocytes are counted in urinary sediment �Signs of urinary irritation- urgency, pain

Antibody associated glomerular Injury �Antibodies to endogenous antigens of the GBM : This mechanism accounts for the renal inury in Goodpasture syndrome a disease caused by antibodies to collagen type IV �Antibodies to non-glomerular antigens : Antigen-antibody complexes found in glomeruli may result from two pathogenetic mechanisms. Ø In situ immune complex formation results from the binding of circulating antibodies– seen in PSGN ( post streptococcal GN) where streptococcal antigens are implantedin the GBM during the infection Ø Circulating immune complexes formed from soluble antigens and corresponding Ab – eg seen in SLE

PSGN �Group A beta- hemolytic streptococci ( streptococcus pyogenes) account for 90% of all GN cases �Typically occurs 1 -4 weeks after a strep throat infection or skin Infection(Impetigo) �Occasionally same clinical-pathological findings may follow staphlococcal infection or even some viral diseases –HBV, HCV or HIV Infection �.

PSGN �The increase in cellularity is due to increasi in epithelial endothelial and mesangial cells �As well as neutrophils in and around capillary loops.

PSGN �Showing increased number of neutrophils , in post-infectious GN

sub-epithelial humps in acute PSGN �Represent epimembranous deposits of immune complexes on the GBM, seen under Electron microscope. �Immunofluorescence shows many other immune complexes not dense enough to be seen by EM �Smaller immune complexes in mesangium

Clinical features of acute PSGN(nephritic syndrome) �Childhood disease �Presents with fever, nausea, oliguria, hematuria, RBC casts in urine, mild protienuria(usually less than < 1 g/ day) peri-orbital edema and mild to moderate HT �As immune complex deposition is assoc. with complement activation C 3 is the complement consumed in both classical and alternate complement pathway. Hence there will be hypo-complementemia

Outcome & long term consequences of acute PSGN �CHILDREN Ø 90% recover within 2 -3 months with conservative therapy aimed at maintaining sodium & water balance. Ø 5 -8% have persistent GN, in much milder form with abnormal urinary findings for 6 -8 months. Ø <1% cases develop Rapidly progressive GN (RPGN) �ADULTS Ø 60% recover promptly Ø 3 -5% develop RPGN

Rapidly progressive glomerulonephritis is reflective of advaned renal pathology �Mostly caused by immunologic mechanisms �Is assoc. with 25% mortality & 40 % progression to chronic end- stage kidney disease � 3 groups Ø A. N. C. A + Cases(Anti-neutrophil cytoplasmic Ab) , most Adult cases , Wegener’s granulomatosis, P. A. N Ø Immune complex mediated – most common form seen in children & young adults < 20 years – seen in post-infectious GN(PSGN) , SLE Ø Anti-GBM Ab – Good Pasteur's syndrome

RPGN or crescentic GN �Crescents are found in more than 50 % of glomeruli represent a sin of severe glomerular injury �Usually starts as focal and segmental necrosis – resulting inrupture of the GBM which allows the entry of inlammatory cells and fibrinogen into theurinary space

Crescentic GN �Early crescents are composed of fibrin , inflammatory cells exudated into the urinary spaces and proliferated epithelial cells of the bowman’s capsule � later these early crescents may get fully fibrotic

Nephrotic syndrome �Protienuria : massive > 3. 5 g/day �There is hypoalbuminemia �Generalized edema : due to reduced oncotic pressure (hypoalbuminemia) �Hyperlipidemia(increased LDL, lipid casts in urine �Affected patients are prone to infection & thrombotic events because of increased urinary loss of serum protiens

Differences between Nephrotic syndrome & Nephritic syndrome �Protienuria ++ to +++ �Hypoalbuminemia + �Edema + to ++ �Hematuria ++ and RBC casts �Oliguria ++++ �No Hyperlipidemia �No Lipiduria �Hypertension + �Nephrotic syndrome �Protienuria in nephrotic range(> 3. 5 g/dl) �Hypoalbuminemia +++ �Edema + to ++ �No hematuria �No Oliguria �Hyperlipidemia �Lipiduria �No Hypertension

Membranous Nephropathy �Is the most common primary cause of Nephrotic syndrome in Adults �Etiol. : Immune complex deposition in glomeruli �Primary – Idiopathic , unknown �Secondary– prolonged antigenemia- SLE, chronic viral hepatitis B & C, cancer pts �Pathology : Diffuse thickening of BM, but no proliferation �No response to steroids �Progresses to end stage renal failure over 10 -15 years

Minimal change disease(Lipoid nephrosis) �Most common cause of nephrotic syndrome in children ( 90 % cases < 5, 50 % of < 10 yrs) �Unknown etiology related to Type IV hypersensitivity �EM scopy shows loss of foot processes of epithelial cells �Responds to steroid therapy

How does SLE affect the kidneys? �Signs of renal disease are found in 50 % of patients at the time of diagnosis � 80% will develop some signs of renal disease at some time during the life span. �SLE is an immune complex mediated disease, immune complexes are deposited in Ø Glomeruli : most frequently affected part, Immune complexes maybe trapped on the sub-endothelial side, inside the GBM, or on the sub epithelial side & mesangium basement membranes lined with sub-endothelial deposits appear thickened , called wireloops Ø Blood vessels Ø Tubules & interstitial spaces

Classification/ stages of lupus nephritis ( SLE) �Class I �Class-II-mesangial GN �Class III- Focal proliferative GN �Class IV- diffuse proliferative GN �Class V- membranous GN �Class VI- Chronic GN �No deposits �Mesangial deposists , mild hematuria �Mesangial & sub-endothelial moderate GN �widespread deposits, severe GN �Subepithelial- nephrotic syndrome �Chronic GN