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Clinical presentations

  • Acute Nephritic syndrome - acute onset of HTN, hematuria, mild proteinuria (ex. post-infection - Strep)
  • Nephrotic syndrome - heavy proteinuria, hypoalbuminemia, severe edema, hyperlipidemia
  • Asymptomatic proteinuria and hematuria - asymptomatic with small amounts of RBCs or protein (ex. familial syndromes affecting glomerular structure)
  • Acute renal failure - acute change in renal function dominated by oliguria or anuria coupled with onset of azotemia)
  • Chronic renal failure - prolonged S&S of uremia, end result of all chronic progressive renal diseases
  • Renal tubular defects - dominated by polyuria, nocturia and metabolic acidosis
  • UTI - bacteria and PMNs in urine, due to infection of either kidney or bladder, F>M
  • Nephrolithiasis - renal colic, hematuria and recurrent episodes
  • Urinary tract obstruction - any partial or complete obstruction of flow of urine from renal pelvis to urethral meatus
  • Congenital renal diseases
  • Hereditary renal diseases - ex. polycystic kidney disease
  • Neoplastic renal disease - derived from renal parenchyma (ex. Wilms or Renal cell ca.)

Azotemia - increased blood levels BUN and Cr that occur as a result of decreased kidney function. Mainly biochemical changes, asymptomatic

Uremia - Azotemia plus a constellation of clinical findings and biochemical abnormalities associated with renal failure - and a corresponding GFR of less than 20. 

Renal disease is mostly multisystem

Complications: Anemia, uremic pericarditis, peripheral neuropathy, pruritis

Kidneys involved in filtration, BP maintenance, regulation of vascular volume, body osmolarity, and blood RBC levels, etc. 

Filtration barrier

  • Fenestrated blood vessels
  • Basement membrane - separates by size and charge (keeps out negatively charged anion molecules such as albumin)
  • Podocyte slit membrane - Nephrin molecules are critical for maintaining this barrier

Selective failure of filtering - only certain molecules get through, ex. albumin

Non-selective - everything gets through -- end-stage renal disease 

Type IV collagen types 1, 2, 3 and anionic heparin sulfate make up the BM

PT - loaded with Mt - very metabolically active and also susceptible to ATN in ischemia

DT - not as metabolically active, mostly involved in water resorption

Brush border - looks like small intestine

Loop of Henle - review function

Congenital Abnormalities

  • 5-10% of individuals born with potentially significant renal problems, can be hereditary
  • Renal dysplasia / hypoplasia are 20% of these
  • Agenesis - when bilateral, Potter sequence results
  • Hypoplasia - failure to develop to normal size
  • Ectopic kidney
  • Horseshoe kidney - ascent is inhibited by the IMA, asymptomatic
  • Renal dysplasia - unilateral is most common presentation - “multicystic kidney”

Unilateral Dysplastic or Multicystic kidney

  • Most common palpable abdominal mass in newborns
  • Failure of ureteric bud to reach renal blastema during embryological development resulting in lack of nephron development --> cysts + lack of normal glomeruli
  • Children are otherwise normal
  • Immature stroma, dysplasia and disorganized cartilage

Renal Cystic Diseases 

AD Polycystic Kidney Disease

  • Adult onset, 4-5th decade
  • Kidneys are always ENLARGED
  • Progressive formation / enlargement of renal cysts with progressive loss of functional parenchyma
  • PKD1 gene defect in 85% of cases, remaining cases have PKD2 (milder, later onset)
  • Mechanism of cyst formation (Mutations of PKD1 --> Defects in cell-cell and cell-matrix interactions --> altered tubular epithelial growth and differentiation --> abnormal ECM, cell proliferation and fluid secretion --> CYST)

Major clinical findings of ADPKD

  • Insidious onset presenting in 4-6th decade, renal insufficiency, HTN, azotemia
  • May exhibit abdominal pain because of cyst enlargement and hemorrhage and hematuria
  • “dragging sensation” - also seen in ovarian masses
  • Chronic renal failure in 50% of patients by age 60
  • HTN accelerates the process
  • M>F, african americans
  • Increased incidence of kidney stones and UTIs
  • Renal cell ca. may develop

Extra-renal manifestations of ADPKD

  • 40% associated with HEPATIC CYSTS (and also spleen, pancreas, lung)
  • 4-10% patients due to subarachnoid hemorrhage secondary to a rupture BERRY ANEURYSM (most common lethal extrarenal manifestation)
  • 25% of patients may have mitral valve prolapse

AR Polycystic Kidney Disease

  • Bilaterally enlarged kidneys with numerous SMALL cysts derived from dilated COLLECTING DUCTS present throughout medulla and cortex
  • Also associated with liver cysts, portal fibrosis and proliferation of bile ducts
  • Defective PKHD1 gene - encodes Fibrocystin
  • Congenital hepatic fibrosis in infantile ARPKD
  • Perinatal subtype is most common (>90% of CDs affected by cysts) - survive only a few hours, also have neonatal, infantile and juvenile forms

Nephronopthisis - Medullary Cystic Disease

  • Onset in childhood - progressive kidney failure (later than ARPKD and earlier than ADPKD)
  • Most common genetic cause of end-stage kidney disease in children and young adults, also most common kidney transplant indication in kids
  • Many clinical variants - one specific feature is retinal involvement - gene deletion also affecting the EYES
  • CM junction - tubulointerstitial disease

Simple Renal Cyst

  • Usually single
  • Occur in renal cortex, esp. on kidney surface
  • Filled with clear fluid
  • No clinical significance

Acquired (dialysis associated) cysts

  • Cortical or Medullary location
  • Numerous - filled with clear fluid
  • Associated with development of renal cell ca.

Glomerular Syndromes basic histological changes

  • Hypercellularity (cellular proliferation and leukocyte infiltration and CRESCENT formation)
  • BM thickening - due to deposition of stuff and due to thickening in and of itself
  • Hyalinization - extracellular deposits of plasma protein
  • Sclerosis - increase in extracellular mesangial matrix

Immune mechanisms of Glomerular injury

  • In situ immune complex deposition
  • Circulating immune complex deposition
  • Cytotoxic abs
  • CMI injury
  • Activation of alternative C’ pathway

In Situ Immune complex deposition

  • Abs directed against intrinsic fixed ags (NORMAL components) of the GBM
  • Endothelial surface, BM
  • Homogenous, LINEAR pattern
  • Ex. Goodpasture’s syndrome

Immune Complex Deposition - Heymann

  • Abs against ags on the basal surface of the visceral epithelial cells (foot processes)
  • HEYMANN Nephritis - ag is a protein called MEGALIN
  • Subepithelial surface, BM
  • GRANULAR, lumpy bumpy pattern
  • Ex. Membranous Glomerulonephritis

Immune Complex Deposition - Ab against “plated” ags

  • Abs react with ags not normally present, but planted there by filtering processes or by affinity for glomerular constituents (bacterial / viral)
  • Drugs and aggregated Ig (Cryoglobulins)
  • Mesangial or Subendothelial localization - GRANULAR pattern
  • Ex. Membranoproliferative (BM) and IgA nephropathy (mesangial)

Circulating Immune Complex Nephritis

  • Glom injury caused by trapping of circulating ag-ab complexes
  • Trapped by filtering process or because of affinity for glomerular components
  • Subendothelial surface and Mesangium
  • Ex. Lupus

Injury to the Glom. due to abs can result from

  1. Deposition of circulating immune complexes
  2. In Situ deposition on BM (anti-GBM)
  3. In Situ deposition on foot processes (Heymann)
  4. Granular characteristic of circulating and in situ immune complex nephritis

Other pathways

  • Abs to glomerular cells - effacement of normal architecture, esp. foot processes leading to normal slit barrier being compromised
  • CMI in Glomerulonephritis (Rapidly Progressive) - Crescentic glomerulonephritis - Platelets, Macrophages, Protease growth factors, Oxidants, etc. --> CK STORM
  • Activation of Alternative C’ pathway - Membranoproliferative glomerulonephritis Type II - MAC attack complex pokes holes in the membrane --> red cells leak out
  • Epithelial cell injury

Mechanisms of continuation of renal disease - once GFR is 30-50% of normal

Focal Segmental Glomerulosclerosis

  • Initiated by adaptive change - i.e. Glom Hypertrophy, Intraglom HTN, Systemic HTN -> cellular proliferation, coagulation, endothelial injury --> focal glomerulosclerosis
  • Renal Ablation focal glomerulosclerosis - ex. loss of renal mass, donation of a kidney --> vicious cycle --> increased risk of RENAL CELL CA.

Tubulointerstitial Damage - result of proteinuria, from direct injury to tubular cells

  • Tubular atrophy, nephron loss, sclerosis

Nephritic and Nephrotic Syndromes 

Acute Nephritis Syndrome - Disruptions / tears in the GBM

  • Acute Proliferative Glomerulonephritis - post-Strep
  • Anti-GBM - Goodpasture syndrome
  • Rapidly Progressive Glomerulonephritis

Acute Proliferative Glomerulonephritis

  • IC glomerulonephritis triggered by response to exogenous bacterial, etc. ag
  • Group A Strep -- treat immediately to prevent Rheumatic fever and Glomerulonephritis
  • Histologically - glomerular hypercellularity, and leukocyte infiltration
  • Subepithelial “hump” - IgG, C3
  • Tears in the BM --> RBCs squeezing through --> hematuria
  • History of pharyngitis, tonsilitis, etc. 1-4 weeks ago
  • More aggressive disease if patient is 20+
  • HTN, Oliguria, Hematuria, RBC casts, Resolution in 6-8 weeks in kids, may also be subclinical, Azotemia (substantial increase in BUN and Cr), mild proteinuria
  • PERIORBITAL EDEMA - hallmark of nephritic syndromes

Clinical course of Acute Proliferative Glomerulonephritis

  • In children, clears in 6-8 weeks, renal biopsy NOT indicated, conservative therapy is enough
  • In adults, more aggressive with 2-3% progressing to Rapidly Progressive GMN and even more progressing to Chronic GMN

Anti-Glomerular BM Disease and Goodpasture

  • Anti-GBM - affects kidney only
  • Goodpasture - Renal and lung involvement - hence often present with hemoptysis because the same type IV collage is present in the BM of the lung capillaries
  • Goodpasture is 2-3x more common
  • Anti-IgG ab localized to glomerular BM will show diffuse LINEAR staining

Rapidly Progressive GMN (RPGN)

Three key findings:

  1. Decline in renal fx - 50% loss or more
  2. Time course is rapid - 3 mos or less
  3. Biopsy findings - CRESCENTIC (extracapillary) glomerulonephritis in 20-80% of gloms

So if you see a patient with hematuria, hemoptysis, HTN and abs, do a renal biopsy!

  • Diverse S&S - oliguria / anuria / hematuria
  • Non-specific signs of acute renal failure - malaise, weakness, lethargy, nausea, vomiting, anorexia, dyspnea, etc.
  • Tx with high-dose corticosteroids and immunosuppressive drugs and plasmapheresis to remove the abs
  • Pts may eventually require dialysis and transplantation


  • Focal disruptions in GBM continuity due to Abs and C’
  • Collapsed glomerular tufts
  • Crescent-shaped mass of proliferating cells and leukocytes
  • Red cells leak out, and with it comes Fibrin --> CRESCENT shape internal to Bowman’s capsule

Types of RPGN

  • Type I - Crescent and Anti-GBM IgG (Goodpasture)
  • Type II (SLE, Hep D, C)
  • Type III - pauci-immune - Crescent with negative antibody and negative fluorescence, possibly p-ANCA positivity (Microscoping polyangitis)

Nephrotic Syndrome - GBM porosity increased

  • PROTEINURIA (3.5g +)
  • Hypoalbuminemia (<3 g)
  • Edema (esp. periorbital)
  • Hyperlipidemia (liver working over time to make albumin, also makes lipoproteins)

Charge-related defects in the BM allow proteins through unlike with Nephritic syndrome where charge was intact so proteins were kept out

The increased GBM porosity is not enough for RBCs to leak through so we mainly see Proteinuria WITHOUT hematuria 

Primary NS - no other systemic disease. Only kidney affected, and most common cause of NS in children

Secondary NS - systemic disease that cause characteristic alterations in the kidney histology - more frequently seen in adults 

Primary Nephrotic Syndrome diseases

  • Minimal change disease (65% of cases in kids)
  • Membranous glomerulopathy (30% of cases in adults)
  • Focal segmental glomerulosclerosis (35% of cases in adults)

Note: No inflammatory component like seen in Nephritic syndromes

Minimal Change Disease (MCD)

  • Lack of any obvious renal abnormalities on Light and Immunofluorescence
  • Epithelial cell (podocyte) foot process effacement is seen minimally by EM
  • Most common cause of NS in children
  • Podocyte effacement leads to selective proteinuria - Albumin only
  • Clinically: edema, slightly larger kidneys, Prednisone (steroid) therapy is VERY effective
  • HTN is rare (by contrast, it is common in post-infectious Nephritic syndrome)

Membranous Glomerulopathy

  • Most common primary cause of NS in adults
  • Diffuse thickening of glomerular capillary wall and GBM - Gloms are affected GLOBALLY
  • Accumulation of electron dense Ig deposits along Subepithelial side, BM - granular
  • Insidious onset of proteinuria, microscopic hematuria
  • Normal-sized kidneys unless disease is advanced, in which case, they will be small
  • HTN occurs in 40-50% of patients (kidney trying to perfuse itself with the rening-angiotensin system)
  • Steroids are NOT EFFECTIVE
  • 40% dev. renal insufficiency, 10% progress to end-stage renal failure
  • Associated with colon, lung cancers and melanomas
  • 3 KEY histological findings - 1) Podocyte effacement, 2) Thick BM, 3) Subepithelial spikes
  • BM thickening --> loses its anionic charge --> NON-SELECTIVE proteinuria

Focal Segmental Glomerulosclerosis (FSGS)

  • Histological marker of progressed chronic glomerular disease --> BAD prognosis
  • 20% of pts follow rapid course --> “malignant focal sclerosis” leading to massive proteinuria and renal failure within 2 years
  • Tubulointerstitial fibrosis is also seen
  • Increased PAS stain indicating GBM sclerosis
  • IgM and C3 in sclerotic segment
  • Some, but not all, gloms are affected (focal) and within each glom only a portion is affected (segmental)
  • Etiology:
  1. Idiopathic - seen in children, does not resolve and progresses
  1. Glomerular ablation nephropathy
  2. HIV nephropathy (“collapsing variant”)
  3. Secondary glomerular scarring in other primary renal diseases

Idiopathic FSGS

  • 10% of children with minimal change disease (MCD) do not respond to tx and progress to FSGS
  • 30-35% of adults with NS (Membranous glomerulopathy) progress to FSGS


  • Higher incidence of hematuria
  • Non-selective proteinuria
  • Responds poorly to steroid therapy
  • Progression to chronic glomerulonephritis, and 50% develop end-stage renal disease within 10 years
  • IgM and C3 in sclerotic segment

HIV-associated Nephropathy

  • Severe form of FSGS in 10-15% of HIV patients
  • High-frequency “collapsing variant” with global involvement
  • Focal cystic dilation of tubule segments
  • Tubuloreticular inclusions in endothelial cells

Mesangial Diseases - Present as either nephrotic or nephritic syndrome

  • IgA nephropathy
  • Membranoproliferative I and III
  • Membranoproliferative II

Common features of Mesangial disease

  • Mesangial cell proliferation and increased matrix
  • Inflammatory component to the glomerular injury
  • Immune complex mediated
  • Chronic RECURRENT disease

IgA Nephropathy

  • Most common type of glomerulonephritis worldwide
  • Young patient (10-30) with gross hematuria that is EPISODIC
  • M>F, 1st degree relatives, caucasians
  1. Berger’s disease - primary Renal IgA nephropathy without systemic disease - however may be associated with Celiac disease (IgA spike that isn’t cleared enough)
  1. Henoch-Schonlein purpura (HSP) - IgA nephropathy associated with systemic disease with skin purpura and involvement of abdominal viscera
  • IgA deposition in mesangial region detected by IF, also C3 deposition
  • Focal / Diffuse mesangial hypercellularity
  • Expansion of mesangial ECM
  • Variable leukocytosis
  • Glomerular capillary BM is NORMAL
  • EPISODIC hematuria often coincides with presence of significant infection at another body site (ex. respiratory)
  • ~30% may have nephrotic range proteinuria
  • Acute nephritic syndrome with HTN seen in 5-10%
  • Acute renal failure only in 1-2% (RPGN)
  • Chronic renal failure in 15-40% over the course of 20 years

Membranoproliferative GN Type I

  • Mesangial proliferation and increased mesangial matrix “splits” the GBM
  • SUBENDOTHELIAL immune deposits along BM
  • Intramembranous dense despoits - marked thickening of the GBM
  • “train tracks” and “lobular” architecture
  • Proliferation - mesangial cells, endocapillary proliferation, and PMNs
  • Mostly affecting children, usually as Nephrotic syndrome with proteinuria
  • Mild HTN
  • Poor response to treatment
  • 50% develop chronic renal failure in 10 years

Etiology of MPGN Type I

Primary - seen in children, idiopathic

Secondary - associated with chronic antigenemia causing immune complex deposition esp. HepC with cryoglobulinemia and others (HepB, cryoglobulinemia, Lupus, etc.) 

Membranoproliferative GN Type II

  • “Dense deposit disease” - continuous intramembraneous dense deposits within the GBM
  • Etiology linked to C3NeF or NEPHRITIC factor - IgG auto-ab that binds C3 convertase leading to continuous activation of the alternative C’ pathway because it shuts off the feedback inhibition C3 convertase
  • Frequently occurs after transplantation - unfortunately another transplant will destroy the new kidney as well
  • Primarily a disease of children
  • Markedly dense deposits within GBM proper --> disruption --> hematuria
  • Patients will have low C’ because the pathogenesis uses up all the C’
  • Primary kidney disease only - no secondary causes like with MPGN I


  • II is much rarer
  • Hematuria is the dominant clinical finding in II
  • II patients more often present with severe renal disease and have poorer prognosis
  • 38% of MPGN II patients develop acute nephritic syndrome (hematuria, HTN, oliguria, edema, etc.) --> renal insuff. --> end-stage renal disease
  • 50% of MPGN patients progress to end-stage renal disease in 10 years

Familial Hematuria syndromes

  • Alport syndrome
  • Thin BM disease
  • + Many others but the above two are 80+% of the cases

Alport Syndrome

  • Genetic defect in genes encoding some chains of Type IV collagen
  • X-linked, 5-20 yo male
  • Structural and functional abnormalities in kidneys, ears and eyes
  • Onset of hematuria, loss of high-pitched hearing, lens dislocation
  • GBM has irregular thickness and multilamination - central density of the BM lost due to collagen defects
  • “Basketweave” appearance

Thin Basement Membrane Disease

  • Hematuria due to thinned GBM that is 150-250 nm (normal is 300-400 nm)
  • Asymptomatic microscopic hematuria
  • Renal fx is normal and pts do not progress to end stage renal disease
  • Other features of Alport syndrome are absent

Chronic Glomerulonephritis

  • 90% of RPGN go on to Chronic
  • Focal Glomerulosclerosis 50-80%
  • IgA, Membranous glomerulopathy, MPGN ~50%
  • Post-infection - 1-2%

Untreated glomerular problems likely to lead to Chronic GN - gloms are fully sclerosed

At this point it is too late to make a diagnosis or to identify the etiology 

Glomerular Disease associated with Systemic Diseases

Nephrotic - diabetes, SLE, Hep C and cryoglobulinemia, etc.

Nephritic - SLE, Goodpasture, etc. 


Henoch-Schonlein purpura - IgA nephropathy

Bacterial endocarditis - Acute proliferative GMN

Goodpasture - Anti-GBM and Crescentic GMN

HIV - collapsing variant of FSGS

Hep C and Cryoglobulinemia - MPGN Type I 

Diabetic Glomerulosclerosis - membranous with mesangial sclerosis

  • 30% of all kidney failure
  • Diffuse glomerulosclerosis, diffuse thickening capillary BM, Nodular glomerulosclerosis (Kimmelstiel-Wilson lesions) - PAS+ nodules
  • Uncontrolled hyperglycemia induces metabolic changes causing deposits and thickening and massive increase in mesangial matrix --> narrows glomerular cap lumen
  • Differential for K-W lesion - rule out Amyloid
  • Starts out with minimal proteinuria - microalbuminuria - reversible and non-progressive
  • Can eventually reach proteinuria - albuminuria - which is irreversible -- trying to keep the patient in the microalbuminuria stage with drug therapy

SLE - multiple histological patterns

Diffuse proliferative, focal proliferative, mesangial, membranous, minimal change

  • Hypercellular glomerulus is stuffed into Bowman’s capsule -- decreased urinary space
  • Full house - IgG, A, M, C’, C3, C4, etc.
  • Membranous variety also has subendothelial dense deposits just like MPGN I/II

SLE Nephritis pattern correlated with prognosis and clinical findings 

Mesangial (Class I and II)

  • Mesangial proliferation
  • Mild proteinuria, mild microscopic hematuria
  • Excellent prognosis

Focal Proliferative (Class III) - Mild

  • Urine hematuria without proteinuria
  • 5% progress to advanced renal failure within 5 years

Diffuse or Focal Proliferative (Class IV) - Severe type

  • Nephritic syndrome with visible hematuria
  • 50% respond to immunosuppressive therapy, 1/3 of the remaining 50% progress to end-stage renal disease

Membranous Lupus Nephritis (Class V)

  • NEPHROTIC syndrome
  • Normal Cr levels with no progression to renal disease in most patients

Pathology of the Renal Tubules and Interstitium 

Acute Tubular Necrosis (ATN)

  • Destruction of tubular epithelial cells and clinically acute suppression of renal fx
  • Most often seen in hospitalized patients
  • Ischemia (hypotension --> DIC, post-transplant) and Direct toxicity (ethylene glycol, myoglobin, heavy metals) are most common causes
  • Urinary obstruction and acute tubulointerstitial nephritis (from NSAID use) are rare causes

Mechanisms of ATN

  • PT injury - highly metabolically active --> injured cells swell and slough causing luminal tubule obstruction
  • Sustained disturbance in blood flow --> reduced glomerular flow and casts form
  • Eventual result is reduced GFR and Oliguria
  • See chart on Page 99 of Packet 6B
  1. Ischemic - affected area is patchy because of blood vessel distribution, sloughed cells and debris forms casts in distal tubules
  1. Toxic - most of the damage is in the PT because toxin is most concentrated there, casts all the way through the rest of the lumen
  • Necrotic tubular epithelial cells are detached and slough into tubular lumen - these casts cause obstruction of flow.... viable cells are swollen and vacuolated
  • In Toxic type especially we see oxalate crystals and FLORID CHANGES in the histology - otherwise ATN toxic vs. ischemia is hard to tell apart


  • Initiating phase - Progressive azotemia, progressive oliguria
  • Maintenance phase - High azotemia, significant oliguria, metabolic acidosis, HYPERkalemia
  • Recovery phase - Decreasing azotemia, Polyuria, HYPOkalemia

Prognosis of ATN is related to underlying etiology - removal of cause or brief insult causes 95% of cases to recover

However, in prolonged cases (hypotension / burns), only 50% recover 

UTI and Pyelonephritis

UTI - 99% bacteria, anywhere along from urethra to renal cortex

Cystitis - inflammation of bladder mucosa - 95% bacterial

Acute Pyelonephritis - acute bacterial infection of kidney

Chronic pyelonephritis - recurrent or continuous long-term chronic infection of kidney 


  • Most commonly gram negative gacteria - E. coli, Proteus, Kelbsiella, Enterobacter
  • Source is often patient’s own fecal flora
  • Vast majority are acute bacterial cystitis
  • Hematogenous spread is rare, requires substantial bacteremia
  • Vast majority are the result of ascending infection
  • Risk factors - diabetes, pregnancy, vesicoureteral reflux

Ascending Infection

  • Bladder outlet obstruction - older males with prostatic hypertrophy
  • Defective Vesicoureteral junction - when bladder contracts normally the oblique ureter is closed during micturition - with this defect, the ureter enters the bladder more horizontally and the patient has some reflux because the valve doesn’t close when the bladder contracts
  • 50% of children with UTIs have this anatomical defect
  • Dx - voiding cysturegram

Acute Pyelonephritis

  • Suppurative infection of kidney caused by bacteria
  • HALLMARK - Patchy interstitial suppurative inflammation throughout the renal cortex and medulla (Coag necrosis)
  • Complications: papillary necrosis, pyenephrosis, perinephric abscess
  • “Pus kidney” and neutrophils
  • Gloms are unaffected -- acute inflammation and PMNs in the interstitium between tubules
  • Associated with - vesicoureteral reflux, pregnancy, indwelling catheters, prostatic hypertrophy, uncontrolled diabetes (high Hb1Ac), Altered immunity as seen in AIDS

Chronic Pyelonephritis

  • Chronic tubulointerstitial inflammation and renal scarring associated with pathological involvement and calyces and pelvis
  • Predisposing conditions - chronic obstructive pyelonephritis, reflux nephropathy
  • HALLMARK - broad-coarse recessed scar on renal cortex (NOTE: in ischemia, we see wedge-shaped lesions no the renal cortex)
  • Dense chronic inflammation
  • Insidious onset, begins in childhood and associated with severe Lower UTI abnormalities
  • Polyuria and Nocturia
  • Proteinuria occurs late with FSGS and loss of renal fx

Tubulointerstitial Nephritis induced by drugs and toxins

Three mechanisms of tubular parenchyma damage

  • Direct damage to tubular epithelium as agent is present and concentrated in urinary flow (ATN, toxic)
  • Trigger an interstitial immune reaction (ex. acute hypersensitivity) - Drug-induced Interstitial Nephritis
  • Analgesic nephropathy

Acute Drug-Induced Interstitial Nephritis

  • Acute renal failure in ~50% of patients
  • May be clinically evident only as progressive increase in serum Cr
  • Urine findings - hematuria, mild proteinuria, pyuria
  • Fever, peripheral eos, skin rash (Erytheme Multiforme) ~15 days AFTER EXPOSURE
  • Sulfa drugs, abx, NSAIDs, etc.
  • Note: Eos and LYs will not get into urine because this is an interstitial process

Analgesic Nephropathy

  • Massive dose excessive intake of Phenacetin-containing analgesic mixtures (usually + aspirin as well)
  • Pathology first in renal medulla (renal papillae) - papillary necrosis
  • Secondary phenomenon seen - cortical tubulointerstitial nephritis
  • Cessation of analgesics + therapy --> return of fx
  • Necrotic papillae seen grossly - also seen in diabetes
  • Diabetic papillary lesions are all of SAME AGE; in Analgesic nephropathy, the lesions are of DIFFERENT AGES

Obstructive Lesions of the Urinary Tract

Key finding is hydronephrosis

  • Thinned renal cortex
  • DIstended renal calyces
  • Dilation of pelvis and ureter


  • Mostly unilateral
  • Intense pain (renal colic), ulceration and bleeding of ureteral mucosa, obstruction of urinary flow
  • Small stones are most hazardous as they can enter the ureter - ureteral spasms cause renal colic (Back pain radiating around the side to the groin)
  • Predisposing factors - increased urinary conc. of stone constituents (Supersaturation)
  • Calcium oxalate and Phosphate most prevalent - mostly present with hypercalciuria

Types of Renal stones

  • Calcium oxalate and Phosphate (mostly idiopathic - serum Ca is normal) - also caused by hypercalcemia situations
  • Magnesium Ammonium Phosphate (Struvite) - UTI (Proteus spp.)
  • Uric Acid - may indicate malignancy like Lymphoma / Leukemia
  • Cystine - hyper-cystinemia (genetic)

Vascular Disorders of the Kidneys

  • Benign Nephrosclerosis
  • Malignant HTN and Accelerated Nephrosclerosis
  • Renal a. stenosis
  • Atheroembolic renal disease

Benign Nephrosclerosis

  • Sequellae of long-standing HTN, side-effect of diabetic glomerulopathy
  • Unusual cause of renal insufficiency by itself
  • Diagnosis made by pathologists
  • Fine, leathery granular surface on kidney (like a football)
  • Hyaline arteriosclerosis with luminal narrowing and glomerular sclerosis and tubular atrophy

Malignant Nephrosclerosis

  • Malignant or Accelerated phase of HTN
  • High DIASTOLIC BP (>130)
  • Extra-renal manifestations - cardiomegaly, papilledema, encephalopathy
  • Hypertensive crisis with loss of consciousness or onset of seizures
  • High mortality
  • Diffuse, fine punctate hemorrhages throughout cortex - “petechiae” on the kidney

Renal artery stenosis

  • Constriction of ONE major renal a. leads to increased Renin secretion because of the macula densa being underperfused and signaling for the JXGA to secrete more renin
  • Renovascular HTN
  • Treatable by re-vascularization
  • Two basic causes - Atheromatous Plaques or Fibromuscular hyperplasia
  • Atheromatous plaques - 70% of cases - occurs at origin of renal a. from abdominal aorta, disease of older males, diabetes, heart disease, etc.
  • Fibromuscular hyperplasia - 30% of cases - intimal thickening in one of the renal arteries in mid-to-distal artery, surgical cure is quite successful

Atheroembolic Renal disease

  • Embolism cholesterol crystals to kidney vessels from rupture of proximal atherosclerotic plaque
  • Disruption of plaque can occur spontaneously or can be iatrogenic (catheterization)
  • Renal injury results from cholesterol embolic occluding arcuate branches of the renal arteries, arterioles and glom caps
  • 5-10% of acute renal failure cases in a hospital
  • REACTIVE FIBROSIS seen due to cholesterol --> obliterates arterial lumen

Renal Neoplasms 


  • Renal Papillary Adenoma
  • Renal Fibroma / Hamartoma
  • Angiomyolipoma (“Fat ball”) - benign, bv’s, muscle - can grow huge - often confused with malignancy causing the kidney to be taken out
  • Oncocytoma - exophytic mass on kidney - intraparenchymal lesion - filled with Mt, benign but can cause mass effect and may be confused with malignancy
  1. They are small, less than 1 cm
  1. Rarely cause clinical problems - often found incidentally and can be mistaken for malignancies

Renal Papillary Adenoma

  • Most common benign kidney neoplasm - essentially a low grade RCC
  • Identical histopathological features as in a RCC
  • Keep tracking it and if it grows over the course of three months, take it out

Renal Cell Carcinoma

  • Malignancy arising from the renal tubules
  • Risk factors - long-term dialysis (acquired renal cystic disease), smoking, obesity, HTN, ADPKD, unoppsed estrogen
  • Onset in 7th-8th decade
  • All 3 present in only 10% of RCC patients
  • Tend to have wide-spread mets before local S&S
  • von Hippel Lindau syndrome is a MAJOR risk factor
  • Hereditary Papillary type (trisomy)
  • Hereditary Clear Cell type (translocation / deletions, vHL)
  • Prognostic factors - Stage and Size (bigger is worse)
  • Stage 1 and 2 - Intrarenal
  • Stage 3 and 4 - invade renal v. and IVC going to the heart and lungs, etc.
  • Spread is mostly HEMATOGENOUS
  • Histological types - Clear cell (may also have eosinophilic anaplasia), Papillary (frond-like papillae), Chromophobe (big nuclei, intensely stained cytoplasm - best prognosis)

Wilms Tumor

  • 4th most common childhood malignancy
  • May present as a very large ab mass
  • 90% patients have no other congenital or genetic abnormalities
  • Remaining 10% have one of Two associated phenotypic syndromes
  1. Overgrowth syndromes - excessive pre- and post-natal somatic growth - BWS - Becketh-Wiedemann Syndrome and isolated hemihypetrophy
  1. Non-overgrowth syndromes - Aniridia, ambiguous genitalia, MR
  • Favorable Histology - Normal histological development, triphasic with no anaplasia
  • Anaplastic histology - DIFFUSE anaplasia confers poor prognosis, focal anaplasia is fine -- anaplasia is associated with resistance to Chemo
  • TRIPHASIC HISTOLOGY - stromal (spindle-shaped cells), epithelial component (immature tubule), blastemal component (densely packed blue cells)
  • Tan to Gray color grossly
  • 90% survive 4 years after diagnosis - Prognosis is related to Stage, Tumor size and patient age
  • Most critical factor is favorable vs. unfavorable histology

Mets to kidney - may present as black lesions - melanoma 

Clinical Pearls 

In situations of ischemia, medullary structures are worst affected - especially the highly metabolically active PT

Teenager with renal failure and retinal dysplasia - Nephronopthisis 

Crescents - histological marker for acute or Rapidly progressive glomerulonephritis

Focal segmental glomerulosclerosis - histological marker for progression of chronic glomerular disease 

Focal Segmental glomerulosclerosis - starts deep in the glom, so it is hard to catch if the biopsy is suboptimal 

Differentiating Classical from Alternative C’ pathway - if you see C1q, etc. then it is classical, because alternative pathway starts straight from C3

Classic C’ pathway - MPGN I

Alternate - MPGN II (C3NeF) 

Bilateral hydronephrosis - lesions is way down at the prostate level

Unilateral - lesions in ureter (cancer, etc.)