Chronic Kidney Disease

Slide 1 · Chronic Kidney

Disease

A clinicopathologic framework

Progressive nephron loss · convergent renal scarring · systemic consequences

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning goals

Define CKD and distinguish azotemia from clinical uremia.

Explain why nephron loss promotes further glomerular and interstitial injury.

Recognize the four main chronic renal lesions and relate them to causes.

Connect loss of renal function to major systemic manifestations.

Slide 3 · CKD is a final common pathway

Persistent nephron loss from diverse renal injuries

A clinical syndrome, not one etiologically uniform histologic disease.

Glomerular · Tubulointerstitial · Vascular injury

Slide 4 · Clinical definition of CKD

Filtration criterion

Persistently diminished GFR

<60 mL/min/1.73 m²

Duration ≥3 months

Kidney-damage criterion

Or persistent albuminuria

Evidence of chronic glomerular damage

May occur before severe filtration loss

Slide 5 · Renal reserve delays recognition

Subclinical renal injury

Loss of functional nephrons

Compensation by survivors

Later fall in renal function

Kidney function may remain clinically inconspicuous until considerable damage has accumulated.

Slide 6 · Four compartments converge in advanced CKD

Glomerulus

Glomerulosclerosis

Tubules

Tubular atrophy

Interstitium

Fibrosis

Vessels

Arterio-/arteriolosclerosis

Damage initiated in one compartment eventually affects the others.

Slide 7 · Cross-talk makes CKD self-amplifying

Glomerular injury

Reduced peritubular flow

Tubular ischemia

Interstitial scarring

The reciprocal pathway also matters: Tubular damage can worsen glomerular injury.

Slide 8 · AKI and CKD: Distinguish the time course

Acute kidney injury

Rapid decline in GFR

Hours to days

Acute fluid/electrolyte imbalance

Chronic kidney disease

Persistent dysfunction

At least 3 months

Progressive nephron loss; Often initially silent

Slide 9 · Azotemia is not the same as uremia

Azotemia

Elevated BUN and creatinine

Biochemical signal of reduced filtration

May be prerenal, renal, or postrenal

Uremia

Clinical syndrome of advanced renal dysfunction

Excretory plus metabolic/endocrine effects

May involve nerves, heart, gastrointestinal tract

Slide 10 · The clinical continuum of CKD

Silent dysfunction

Persistent renal impairment

Progressive systemic effects

Severe symptomatic uremia

Severity depends on both remaining renal function and associated complications.

Slide 11 · The etiologic map of CKD

Metabolic

Diabetic nephropathy

Vascular

Nephrosclerosis and ischemia

Glomerular

Chronic glomerular disease

Tubulointerstitial

Chronic pyelonephritis / injury

Hereditary and developmental disorders can also reduce effective nephron mass.

Slide 12 · Diabetes and vascular disease dominate

Diabetic and vascular kidney disease as the most common CKD antecedents.

Both may damage several renal compartments over time.

Histologic scarring is often nonspecific by the time renal failure is advanced.

Slide 13 · Diabetic nephropathy can culminate in CKD

Diabetes mellitus

Progressive renal injury

Loss of functioning nephrons

Chronic renal insufficiency

Diabetic nephropathy is described as a leading cause of chronic kidney failure; Detailed diabetic lesions belong to its own chapter.

Slide 14 · Vascular narrowing creates ischemic injury

Arterial/arteriolar thickening

Reduced luminal caliber

Chronic parenchymal ischemia

Glomerular + tubular scarring

Nephrosclerosis illustrates how vascular disease ultimately becomes a pan-renal lesion.

Slide 15 · Glomerular diseases may end in sclerosis

Different primary or systemic glomerular insults may destroy nephron units.

Progressive segmental and global glomerulosclerosis can follow.

The remaining nephrons experience compensatory hemodynamic stress.

Slide 16 · Chronic pyelonephritis produces an alternate pattern

Reflux / chronic infection-related injury

Calyceal distortion + polar scars

Tubulointerstitial fibrosis

Progressive loss of renal function

Calyceal damage differentiates chronic pyelonephritis from many other scar-forming renal diseases.

Slide 17 · Congenital nephron deficit can matter lifelong

Agenesis

Unilateral renal agenesis

Solitary kidney undergoes compensatory enlargement

Adaptive sclerosis may develop

Hypoplasia

True renal hypoplasia

Reduced developmental nephron mass

Associated with later CKD susceptibility

Slide 18 · Cystic disorders can also cause chronic loss

Some inherited cystic disorders progressively replace renal parenchyma.

Autosomal dominant polycystic kidney disease is an important CKD cause.

Acquired cystic changes may occur after end-stage kidney disease; Distinguish cause from consequence.

Slide 19 · Primary lesion predicts initial clues

Glomerular

Proteinuria / hematuria

Tubular

Polyuria / nocturia

Interstitial

Tubular dysfunction, chronic scarring

Vascular

Hypertension / ischemic injury

These clues become less specific as multi-compartment scarring accumulates.

Slide 20 · Adaptive hyperfiltration: Short-term benefit, long-term cost

Fewer nephrons → higher workload per surviving nephron

Compensatory filtration helps preserve total GFR but exposes remaining glomeruli to injury.

Functional adaptation does not replace lost nephron mass.

Slide 21 · From nephron loss to glomerular hypertension

Reduced renal mass

Glomerular hypertrophy

↑ flow and capillary pressure

Podocyte/endothelial stress

This sequence is particularly evident in adaptive FSGS after reduced nephron number.

Slide 22 · Podocyte loss becomes a protein leak

Podocyte stress and injury

Foot-process / slit disruption

Podocyte detachment

Proteinuria

Podocytes have limited capacity for replication; Depleted podocyte coverage is difficult to restore.

Slide 23 · Proteinuria can injure tubules

Increased filtered proteins

Tubular cell activation

Cytokines and chemokines

Interstitial inflammatory response

Protein is both a clinical marker of glomerular damage and a potential participant in tubular injury.

Slide 24 · Interstitial fibrosis completes a vicious circle

Tubular injury

Inflammatory mediators

Extracellular-matrix accumulation

Permanent nephron attrition

Fibrosis reduces functional parenchyma, which sustains maladaptive responses in surviving nephrons.

Slide 25 · Peritubular hypoperfusion accelerates damage

Sclerotic glomeruli / small-vessel disease

Reduced downstream blood supply

Tubular ischemia

Atrophy + interstitial fibrosis

Reduced peritubular perfusion links vascular and glomerular lesions to tubular destruction.

Slide 26 · Two pathologic engines of progression

Glomerular compartment

Glomerulosclerosis

Segmental → global obsolescence

Progressive decline in filtration surface

Tubulointerstitial compartment

Tubulointerstitial fibrosis

Tubular dropout and fibrous replacement

Strong association with functional decline

Slide 27 · The feed-forward cycle of chronic injury

Nephron loss

Hyperfiltration + hypertension

Podocyte / endothelial injury

More glomerulosclerosis

The cycle can persist even when the initial insult is no longer active.

Slide 28 · Why reduced nephron number has consequences

Adaptive glomerular hypertrophy sustains filtration initially.

Increased intraglomerular pressure contributes to protein leakage and sclerosis.

Further nephron loss increases stress on the remaining units.

This shared mechanism applies across otherwise different renal diseases.

Slide 29 · Podocyte injury versus mesangial scarring

Initiating structural failure

Podocyte injury

Foot-process effacement or loss

Filtration barrier permeability ↑

Established chronic lesion

Sclerosing response

Mesangial matrix accumulation

Segmental then global glomerular obliteration

Slide 30 · What drives interstitial scarring?

Ischemia

Reduced capillary supply

Inflammation

Persistent interstitial immune response

Protein stress

Tubular activation by filtered proteins

Matrix deposition

Fibroinflammatory remodeling

These are interacting processes, not four independent disease entities.

Slide 31 · Advanced CKD has a nonspecific histologic quartet

Glomerulosclerosis · Interstitial fibrosis · Tubular atrophy · Arteriosclerosis

The pattern shows chronicity and loss of nephron mass; It may not identify the initiating etiology.

Interpret morphology alongside the clinical and imaging history.

Slide 32 · Glomerulosclerosis: Segmental versus global

Segmental glomerulosclerosis

A portion of the tuft is scarred

Global glomerulosclerosis

Entire tuft is scarred

Schematic only — capillary tuft profiles simplified; Not a photomicrograph.

Slide 33 · Glomerular scarring can evolve

Compensatory enlargement

Epithelial/endothelial injury

Matrix deposition

Segmental then global sclerosis

Sclerosis represents chronic structural remodeling rather than an intact filtration barrier.

Slide 34 · What tubular atrophy implies

Tubular epithelial loss

Reduced functional epithelium

Atrophic tubules

Smaller or simplified profiles

Tubular dropout

Loss of renal epithelial units

Surrounding fibrosis

Replacement of parenchyma by matrix

Atrophy is one of the reproducible endpoints of chronic kidney damage.

Slide 35 · Interstitial fibrosis tracks functional injury

Peritubular ischemia / inflammation

Tubular injury

Fibrous matrix expansion

Loss of renal reserve

The extent of tubulointerstitial damage often correlates more closely with decline in function than glomerular injury.

Slide 36 · Renal vessel lesions: Hyaline and fibroelastic

Hyaline arteriolosclerosis

Fibroelastic arterial thickening

Hyaline wall thickening; Lumen narrowed

Arterial intimal / medial remodeling

Slide 37 · Surface granularity reflects microscopic scars

Small-vessel narrowing

Patchy subcapsular ischemia

Sclerotic glomeruli + tubular loss

Finely granular cortex

This is a characteristic gross correlate of nephrosclerosis, not a unique sign of every CKD cause.

Slide 38 · Fine granularity versus coarse polar scars

Vascular pattern

Nephrosclerosis

Fine, even cortical granularity

Patchy cortical ischemic atrophy

Reflux / infection pattern

Chronic pyelonephritis

Coarse corticomedullary scars

Blunted and distorted underlying calyces

Slide 39 · Acquired atrophy versus true hypoplasia

Chronically damaged kidney

Acquired chronic scarring

Fibrosis and distorted architecture

Often uneven cortical scarring

Underdeveloped kidney

True congenital hypoplasia

Reduced number of renal lobes / pyramids

No acquired scars by definition

Slide 40 · Anatomical diagnosis needs context

Glomerular biopsy

Sclerosis: Extent and distribution

Tubulointerstitial biopsy

Fibrosis / atrophy burden

Vascular biopsy

Wall thickening / ischemic patterns

Imaging / history

Size, scars, calyces, chronology

The shared chronic endpoint can obscure the primary renal disease.

Slide 41 · Morphologic interpretation: Common pitfalls

Do not infer the original cause of CKD from global sclerosis alone.

Adaptive segmental sclerosis can complicate a primarily nonglomerular disorder.

Coarse scars with deformed calyces suggest chronic pyelonephritis.

Renal ischemia may produce combined glomerular, tubular, and interstitial lesions.

Slide 42 · CKD may be silent before uremia

Persistent kidney damage

Slow decline in functional reserve

Accumulation of excretory deficits

Multisystem manifestations

An absence of early symptoms does not establish normal renal structure or function.

Slide 43 · GFR and albuminuria answer different questions

Filtration

GFR

Functional filtration capacity

May decline gradually with nephron loss

Damage marker

Albuminuria

Persistent glomerular barrier damage

May be present while filtration is relatively preserved

Slide 44 · Urine findings can suggest where injury began

Albuminuria

Glomerular filter injury

Hematuria

Possible glomerular disease

Polyuria / nocturia

Tubular dysfunction

Mild proteinuria + scars

Possible tubulointerstitial injury

No single urine finding specifies the full chronic renal histologic pattern.

Slide 45 · Acute azotemia requires another differential

Prerenal physiology

Prerenal azotemia

Renal hypoperfusion without primary tissue injury

May reverse after perfusion correction

Postrenal obstruction

Postrenal azotemia

Obstruction distal to the kidney

May reverse with relief of obstruction

Slide 46 · Case: Albuminuria before severe azotemia

A patient has persistent albuminuria but preserved filtration capacity on routine assessment.

Does the source definition permit CKD?

Which compartment is likely generating the urinary finding?

Why are serial measurements important?

Teaching interpretation

Yes—persistent albuminuria qualifies in the Robbins definition; It suggests filtration-barrier injury, and chronicity must be established.

Slide 47 · Case: Solitary kidney and later proteinuria

An adult born with one kidney develops proteinuria after years of preserved renal function.

What was initially compensatory?

What hemodynamic stress emerges?

What secondary glomerular lesion is plausible?

Teaching interpretation

Glomerular hypertrophy and hyperfiltration; Intraglomerular hypertension; Adaptive segmental sclerosis.

Slide 48 · Fluid and electrolyte manifestations

Water deficit

Dehydration

Salt and water retention

Edema

Potassium handling

Hyperkalemia

Acid handling

Metabolic acidosis

The clinical balance varies with residual tubular function and stage of disease.

Slide 49 · Hyperkalemia and acidosis reflect excretory failure

Reduced functional nephron mass

Impaired homeostasis

Potassium / acid retention

Systemic complications

Hyperkalemia and metabolic acidosis are major CKD manifestations listed Table 20.1.

Slide 50 · Mineral imbalance affects bone

Phosphate retention

Calcium–phosphate imbalance

Secondary hyperparathyroidism

Renal osteodystrophy

Robbins groups hyperphosphatemia, hypocalcemia, parathyroid changes, and skeletal disease together.

Slide 51 · Hematologic complications of CKD

Red-cell consequence

Anemia

Common hematologic manifestation

Associated with chronic renal dysfunction

Hemostatic consequence

Abnormal bleeding

Bleeding is listed among uremic manifestations

Can occur despite lack of severe thrombocytopenia

Slide 52 · Cardiovascular complications reinforce CKD burden

Renal dysfunction

Hypertension / fluid burden

Cardiac stress

Heart failure / pulmonary edema

Cardiomyopathy and congestive heart failure are also prominent manifestations.

Slide 53 · Uremic pericarditis is an advanced consequence

Uremic patients may develop fibrinous pericardial inflammation.

It reflects systemic effects of severe renal dysfunction.

Do not interpret pericarditis as a defining finding of early CKD.

Slide 54 · Gastrointestinal manifestations of uremia

Nausea

Systemic uremic symptoms

Vomiting

Metabolic / gastrointestinal effects

Mucosal inflammation

Esophagitis, gastritis, colitis

Bleeding

Potential gastrointestinal complication

GI symptoms should be integrated with biochemical and other systemic findings.

Slide 55 · Neuromuscular manifestations of uremia

Myopathy

Muscular dysfunction

Neuropathy

Peripheral nerve involvement

Encephalopathy

Central nervous system dysfunction

Clinical implication

Multisystem disease, not isolated azotemia

These complications indicate consequences beyond the renal parenchyma.

Slide 56 · The skin may signal advanced dysfunction

Pruritus is listed among dermatologic manifestations.

Sallow discoloration and dermatitis can occur.

Cutaneous findings are supportive clinical clues rather than specific CKD tests.

Slide 57 · Systemic effects: Four key domains

Cardiopulmonary

Hypertension · edema · heart failure

Hematologic

Anemia · abnormal bleeding

Mineral–bone

Hyperphosphatemia · osteodystrophy

Neurologic / GI

Neuropathy · nausea · encephalopathy

CKD is a systemic illness once renal excretory and endocrine functions fail.

Slide 58 · APOL1 risk is ancestry-associated, not deterministic

Textbook association

Population association

Higher CKD frequency in some groups with African ancestry

High-risk APOL1 variants may contribute

Interpretation limit

Individual inference

Ancestry is not a renal diagnosis

Genetic susceptibility does not replace cause-specific evaluation

Slide 59 · Why CKD can progress after the initiating insult

Initial glomerular, vascular or tubule injury

Critical reduction in nephron mass

Maladaptive surviving-nephron workload

Ongoing sclerosis and fibrosis

The source emphasizes shared, secondary mechanisms once substantial nephron loss has occurred.

Slide 60 · Renin–angiotensin system blockade: A mechanism target

Inhibition of the renin–angiotensin system in progressive glomerulosclerosis.

Reducing intraglomerular hypertension can interrupt maladaptive injury.

This is a pathophysiologic principle, not an individualized prescribing algorithm.

Slide 61 · Case: Coarse scars and nocturia

Imaging shows asymmetrically scarred kidneys with blunted calyces. The patient has nocturia and longstanding hypertension.

Which chronic injury pattern best fits?

Why might nocturia develop?

Which microscopy findings would support the impression?

Teaching interpretation

Chronic pyelonephritis / reflux nephropathy; Impaired concentrating ability; Tubular atrophy, interstitial fibrosis and chronic inflammation.

Slide 62 · Case: Fine cortical granularity and ischemic damage

A kidney has a finely granular cortical surface; Arterioles show hyaline thickening and narrowed lumens.

Identify the dominant initiating compartment.

Explain the cortical granularity.

Predict the other compartments affected.

Teaching interpretation

Vascular nephrosclerosis; Patchy ischemic cortical scars; Secondary glomerulosclerosis and tubular/interstitial injury.

Slide 63 · Case: Multisystem uremia

A patient with longstanding renal disease develops pruritus, nausea, anemia and pulmonary edema.

Is azotemia alone sufficient to describe the syndrome?

Which body systems are represented?

What unifies these manifestations?

Teaching interpretation

No; This is systemic uremic illness involving dermatologic, gastrointestinal, hematologic and cardiopulmonary systems due to advanced renal dysfunction.

Slide 64 · Integrating pathology with clinical signals

Sclerosis + proteinuria

Consider glomerular injury and adaptation

Atrophy + nocturia

Consider tubular dysfunction

Arteriolar narrowing

Consider chronic ischemia

Fibrosis + declining GFR

Chronic renal parenchymal loss

Use the full pattern; Avoid single-finding diagnosis.

Slide 65 · Diagnostic interpretation: What CKD does and does not say

Syndrome-level conclusion

CKD establishes

Chronic kidney dysfunction or damage

Risk of progressive loss of renal function

Need to assess systemic effects

Etiologic questions remain

CKD alone does not establish

The initiating histologic diagnosis

Whether injury is active or burned out

A single universal gross appearance

Slide 66 · Five source-grounded conclusions

CKD is a shared outcome of chronic renal insults and nephron loss.

Surviving glomeruli hyperfilter; Adaptive injury can accelerate sclerosis.

Tubulointerstitial fibrosis strongly relates to loss of renal function.

Glomerular, tubular, interstitial and vascular lesions converge.

Severe CKD produces multisystem uremic manifestations.

Slide 67 · Self-assessment: Locate the lesion

A progressively scarred kidney shows glomerulosclerosis, tubular atrophy, interstitial fibrosis and arterial thickening.

Can the cause be assigned by the quartet alone?

Which lesion may best correlate with functional decline?

Name one route by which vascular disease causes glomerular scarring.

Teaching interpretation

No. Tubulointerstitial damage is often particularly informative. Vascular lumen narrowing causes ischemia and secondary glomerular/tubular injury.

Slide 68 · Primary teaching sources

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 20, The Kidney.

Clinical Manifestations of Renal Diseases + Table 20.1 (pp. 814–815).

Mechanisms of Progression in Glomerular Diseases (pp. 822–823); adaptive FSGS (pp. 831–832).

Nephrosclerosis (pp. 851–852); Chronic Kidney Disease (p. 855).

Chronic pyelonephritis and developmental anomalies: adjacent chapter context.