MODULE 5

RENAL DISEASES
In Module 1 you had an in-depth discussion on normal renal anatomy and physiology,
particularly on the formation of urine, to give you an idea on how each structure contributes to the
normal composition of urine. This module will focus on the pathologic consequences of alterations
on those structures. This would elaborate on how it would manifest in the patient and how it would
affect the urinalysis results thereby facilitating its detection or diagnosis.

At the end of this module, the students will be able to:

• Categorize the various renal diseases
• Discuss the pathogenesis of renal diseases
• Describe the clinical features of renal diseases
• Correlate with urinalysis results

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
1
 UNIT 1: RENAL DISEASES
At the end of this unit, students should be able to:

• Classify various renal diseases according to structure implicated.

• Discuss general mechanisms of damage to renal structures resulting to disease.
• Describe clinical features and pathogenesis of specific renal diseases.

ENGAGE – RECALL OF ANATOMY

CLASSIFICATION OF RENAL DISEASES

Renal diseases are classified based on the

morphological component initially affected. However,
other components may be affected due to structural and
functional interdependence of each component to one
another.

Glomerular Diseases are usually immune-

mediated causing deposition of immune complexes on the
glomerulus thereby resulting to inflammation or damage.
Tubular and tubulointerstitial diseases are commonly
caused by infectious and toxic substances taken by the
patient. Vascular diseases affect renal perfusion in the
kidneys to which normal renal function is dependent.

The presence of either of these renal diseases may

result to renal failure that may be acute or chronic
depending on the extent or severity of damage. Acute renal
failure is characterized by a sudden loss of renal function
with a high mortality rate but is often reversible if treated
immediately. Chronic renal failure, on the other hand, is
characterized by progressive and irreversible loss of renal
function.

The next unit will discuss renal stones or calculi

which can occur in any segment of the urinary tract
Figure 1.1 Overview of Renal Diseases
depending where stasis occurs.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
2
 EXPLORE – UNLOCKING CONCEPTS
CAUSES AND GENERAL MECHANISMS OF DAMAGE

PATHOGENESIS OF GLOMERULAR DISEASES

The primary mechanism of glomerular damage is immune-mediated. Damage occurs

either due to the deposition of immune complexes on the glomerulus or antibodies directly
reacting to glomerular tissue. Immune complexes are formed as a result of exposure to
antigens. These immune complexes are then trapped in the glomerular tuft and may activate
the complement system resulting to cell lysis of cells in the glomerulus. Another immune-
mediated mechanism, is when antibodies cross react with the glomerular tissue antigens or
antigens that currently reside in the glomeruli (ex. drugs, infectious agents).

Figure 1.2 Deposition of immune complexes

Another mechanism of glomerular damage results from the presence of chemical

mediators and toxic substances. Although immune complexes are not the culprit this time,
they can induce this mechanism resulting to an inflammatory response. These mechanisms
cause clinical features or symptoms that characterize glomerular damage. When these
symptoms occur together, these group of symptoms is called a syndrome. In glomerular
diseases the patient may either experience nephritic or nephrotic syndrome

Nephritic syndrome refers to a group of clinical findings indicative of glomerular

damage resulting from an inflammatory process. Nephritic syndrome includes hematuria,
hypertension, oliguria, azotemia, mild proteinuria and mild edema. It is primarily seen in
primary glomerular diseases and in glomerular diseases secondary to systemic diseases. The
severity of these symptoms depends on the number of glomeruli involved, the mechanism of
injury and the onset of disease.

Nephrotic Syndrome indicates adverse glomerular changes brought about by non-

inflammatory mechanisms. It is characterized by proteinuria (>3.5 g/day), hypoalbuminemia,
generalized edema, hyperlipidemia and lipiduria. Due to the increased glomerular
permeability, substances such as albumin, immunoglobulins, complement cofactors,
coagulation factors and lipids become elevated in urine. Albumin is the predominant protein
lost in urine resulting to hypoalbuminemia and proteinuria. The patient becomes susceptible
to infections and thrombotic complications due to the loss of immunoglobulins, complement
cofactors and coagulation factors.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
3
 Hyperlipidemia and lipiduria result from the increased lipid synthesis in the liver and
a decreased lipid catabolism. Although the exact mechanism remains unknown, an elevation
in the plasma concentration of triglycerides, cholesterol, phospholipids and very-low-density
lipoproteins are observed. These lipids are then able to pass through the glomerulus and are
found freely floating in urine, withing renal tubular cells or withing renal casts.

Generalized edema is caused primarily by

sodium retention associated with the increased
reabsorption of sodium and water in the distal
convoluted tubules. Hypoalbuminemia plays a
minor role in causing edema since the loss of
proteins in plasma reduces its oncotic pressure
eventually causing the movement of fluid into the
interstitial tissues. Soft and pitting edema is
commonly observed in the eyes or legs. In severe
cases, pleural effusions and ascites may manifest.
Aside from glomerular diseases, nephrotic
syndrome can also be observed in patients with Figure 1.3 Soft and pitting edema
systemic diseases and those who have taken
nephrotoxic agents.

MORPHOGICAL CHANGES IN GLOMERULAR DISEASES

In disease states, one or more morphological changes occur in the glomerulus

causing glomerulonephritis and may serve as the basis of characterizing these diseases.
These morphological changes include cellular proliferation, leukocytic infiltration, glomerular
basement membrane thickening and hyalinization with sclerosis.

Leukocyte infiltration is characterized by the infiltration of neutrophils and

macrophages as form of chemotactic response commonly observed in some types of acute
glomerulonephritis.

Cellular proliferation is characterized by an

increase in the number of endothelial cells, mesangial
cells and podocytes in the glomerular tuft. Cellular
proliferation may be segmental, focal, or diffuse.
Segmental cellular proliferation involves only a part of
each glomerulus. Focal cellular proliferation involves
only a certain number of glomeruli in the kidney. Diffuse
cellular proliferation involves all glomeruli in the kidneys.
Figure 1.4 Cellular Proliferation

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
4
 Glomerular basement membrane thickening is
caused by deposition of immune complexes or fibrin
on the basement membrane. This is true in most
cases, but in diabetic glomerulosclerosis the
basement membrane thickens without any evidence
of deposition of materials.

Figure 1.5 Basement Membrane Thickening

Hyalinization is characterized by the

accumulation of a homogenous eosinophilic material in
the glomeruli resulting to the loss of its structural detail.
Eventually the accumulation of these substances
causes the glomerulus to become sclerotic which is
irreversible.

Figure 1.6 Hyalinization with Sclerosis

EXPLAIN– LET’S GET INTO DETAILS

SPECIFIC RENAL DISEASES

TYPES OF GLOMERULAR DISEASES

PRIMARY GLOMERULAR DISEASES SECONDARY GLOMERULAR DISEASES

Acute glomerulonephritis Systemic Diseases
Rapidly progressive glomerulonephritis Diabetes Mellitus
Membranous glomerulonephritis Systemic Lupus Erythematosus
Minimal change disease Amyloidosis
Focal Segmental glomerulosclerosis Vasculitis
Membranoproliferative glomerulonephritis Bacterial Endocarditis
IgA Nephropathy Hereditary Disorders
Chronic glomerulonephritis Alport’s syndrome
Fabry’s Disease

Acute glomerulonephritis (AGN) can either streptococcal or non-streptococcal. Acute

poststreptococcal glomerulonephritis is a common glomerular disease that occurs 1 – 2
weeks after a streptococcal infection of the skin or throat. The delay in the manifestation of
glomerular damage accounts for the formation of antibodies against the M protein in the cell
wall of some strains of group A beta-hemolytic streptococci. The immune complexes formed
then deposits on the glomerulus resulting to morphological changes such as diffuse cellular
proliferation (endothelial and mesangial cells), leukocytic infiltration and interstitial
swelling. The patient experiences acute nephritic syndrome and majority would recover from

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
5
 the disease. However, this may progress to chronic glomerulonephritis. On the other hand,
non-streptococcal glomerulonephritis is a rare type of AGN caused by other etiologic agents
that shares the same clinical feature.

Figure 1.7 Morphological Changes in Poststreptococcal AGN

Rapidly progressive glomerulonephritis or crescentic glomerulonephritis is caused by

the formation of antibodies against the glomerular basement membrane that has a high
chance of progressing to chronic glomerulonephritis (90% of cases). It usually develops after
an infection, as a result of an underlying systemic disease or idiopathically. The patient
experiences all symptoms in acute nephritic syndrome except oliguria. Glomerular changes
associated with this condition include cellular proliferation, leukocytic infiltration, fibrin
deposition and “wrinkling” of the basement membrane.

Figure 1.8 Morphologic changes in CGN

Membranous Glomerulonephritis (MGN) is a major cause of nephrotic syndrome

among adults with a 50% chance of progressing to chronic glomerulonephritis. It is caused
by the deposition of immune complexes and activation of the complement leading to
glomerular basement membrane thickening. Majority of MGN (85%) is idiopathic while the
other possible causes include immune-mediated diseases, underlying conditions, exposure
to toxic metals (ex. gold and mercury) and nephrotoxic drugs (ex. penicillamine). Aside from
nephrotic syndrome, hematuria and hypertension manifests in patients with MGN. The

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
6
 thickening of the basement membrane encloses the immune deposits resulting to a diffuse
loss of foot processes. Aside from that, hyalinization and sclerosis reduce the capillary lumen
diameter.

Minimal change disease (MCD), on the other hand, is the major cause of nephrotic
syndrome among children. It differs from MGN in terms of treatment and recovery, MCD
responds well to corticosteroid therapy and has a better prognosis than MGN. It is caused by
a dysfunction in T cell immunity resulting to the loss of the polyanions (heparan sulfate) that
is responsible for the “shield of negativity” of the glomeruli. Upon routine microscopy, the
glomeruli look normal. However, upon closer inspection using electron microscope, there is
loss of podocyte foot processes and vacuolization of the cytoplasm.

Figure 1.9 Difference between MGN and MCD

Focal Segmental glomerulosclerosis (FSGS) differs from MCD as it has little to no

response to corticosteroid therapy with 50-80% progressing to chronic glomerulonephritis. It
is theorized that it is caused by an unknown circulating systemic factor and therefore may
recur after transplantation. Patients with FSGS manifest nephrotic syndrome with variable
proteinuria (subnephrotic to nephrotic), hematuria, hypertension and reduced glomerular
filtration rate. Glomerular changes include focal or segmental sclerosis, hyaline and lipid
deposition, mesangial cell proliferation, a collapsed basement membrane, diffuse loss of foot
processes and diffuse IgM and C3 deposits.

Figure 1.10 Morphological Changes in FSGS

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
7
 Membranoproliferative glomerulonephritis
(MPGN) is a slow and progressive disease that has a
50% chance of developing to chronic
glomerulonephritis. Similar to FSGS, it may also recur
after renal transplant. It is caused by deposition of
immune complexes or complement activation.
Patients manifest nephrotic syndrome, hematuria
and subnephrotic proteinuria (<3.5g/day).
Glomerular changes observed include cellular
proliferation in the mesangium causing the glomeruli
to appear lobular, leukocytic infiltration and
thickening of the basement membrane (IgG and Figure 1.11 Lobular Appearance of the
Glomerulus in MPGN
Complement deposits).

IgA Nephropathy also known as Berger’s Disease is the most common cause of
primary glomerulonephritis that primarily affects children and young adults with 30-50% of
the cases progressing to chronic glomerulonephritis. It occurs 1 – 2 days following a mucosal
infection (respiratory, gastrointestinal and urinary tract) that stimulates IgA synthesis
resulting to its increase in circulation. The circulating IgA complexes/aggregates are trapped
or engulfed by mesangial cells. These IgA complexes then activates the alternative
complement pathway causing glomerular damage. Patients with IgA nephropathy manifest
nephritic syndrome and recurrent hematuria. Glomerular changes include IgA deposition,
leukocytic infiltration and complement deposits.

Figure 1.12 Pathogenesis of IgA Nephropathy

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
8
 As you may have noticed, some of these conditions has the probability of developing
to chronic glomerulonephritis. In fact, 80% of cases of chronic glomerulonephritis had some
form of glomerulonephritis before while the rest are unrecognized or subclinical. Clinical
features include edema, hypertension, proteinuria, azotemia and cerebral or cardiovascular
conditions. Glomerular changes include hyalinization, tubular atrophy, interstitial fibrosis and
leukocytic infiltration. Patients with chronic glomerulonephritis often require lifelong dialysis
or renal transplantation to manage or treat these clinical findings. Otherwise, uremia and other
pathologic changes may result to the death of the patient.

Table 1.2 Summary or Typical Urinalysis results of some types of Glomerulonephritis

Glomerular diseases may occur secondary to systemic diseases.

Diabetes mellitus is a metabolic disease characterized by the inability to metabolize

glucose due a defect in the production or response to insulin. Eventually, this causes
alterations in the metabolism of fat and proteins. Clinical features of diabetes mellitus include
hyperglycemia, glucosuria, proteinuria (subnephrotic to nephrotic) and hypertension. Cellular
proliferation in the mesangium, thickening of the basement membrane and sclerosis are
glomerular changes that occur in diabetes mellitus.

Systemic lupus erythematosus is an autoimmune disorder characterized by the

production of autoantibodies. Almost all patients with SLE manifest kidney problems as a
result of immune complex deposition and complement activation. Clinical features include
acute nephritic syndrome with recurrent hematuria and nephrotic syndrome eventually
progressing to chronic renal failure.

Amyloidosis refers to a group of systemic diseases that result to the deposition of

amyloid on the glomeruli and effectively destroying it. Amyloid is a proteinaceous substance
composed of 90% fibril protein and 10% glycoprotein. Patients with amyloidosis develop
nephrotic syndrome and chronic renal failure.

Examples of glomerular diseases secondary to hereditary disorders are Alport’s

syndrome and Fabry’s disease. Alport’s syndrome causes the basement membrane to
become lamellated resembling thine plates or scales. Patients with Alport’s syndrome

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
9
 develop nephrotic syndrome and chronic renal failure. Fabry’s disease causes the deposition
of glycosphingolipids (cerebroside trihexoside) on the glomeruli.

TUBULAR DISEASES

Tubular diseases can occur as either a result of necrosis or a preexisting condition

causing tubular dysfunction. Tubular necrosis may be caused decreased blood flow in the
kidneys resulting to ischemia or direct damage to the tubules by toxic substances.

Tubular dysfunction may result from a primary renal disease or may be secondary to
a preexisting condition. The dysfunction may involve a single pathway with only one solute
type affected or may involve multiple pathways, thereby affecting a variety of tubular
functions. Dysfunction may occur in different segments of tubules, therefore unaffected parts
and glomerular function remains normal. Common tubular dysfunction includes Fanconi
syndrome, cystinosis and cystinuria, renal glucosuria, renal phosphaturia and renal tubular
acidosis.

ACUTE TUBULAR NECROSIS (ATN)

This is characterized by reversible destruction of the renal tubular epithelium with 50%
of cases resulting from surgical procedures. Once the cause of the damage is treated or
resolved, the patient may recover completely.

Renal tubular necrosis presents in three (3) phases: onset, renal failure and recovery.
The onset of the disease is rather abrupt after a hypotensive event or subtle after exposure
to a nephrotoxic substance. Eventually either of these would develop to renal failure
characterize by azotemia, hyperkalemia, metabolic acidosis and oliguria (<400 mL of
urine/day). During the recovery phase, urine output steadily increases as much as 3 liters per
day. Diuresis in this phase indicates that the glomerular filtration rate is returning to normal
prior to the recovery of the tubular epithelium. This results to continued loss of large amounts
of water, sodium and potassium until tubular function is restored and azotemia is resolved.

ATN can be classified as either Ischemic or toxic depending on the cause of injury and
the epithelium involved.

Ischemic Acute Tubular Necrosis

This is a focal type of tubular disease characterized by tubular basement

membrane disruption (ex. tubulorrhexis) resulting from the complete necrosis of
tubular cells exposing the renal interstitium to the tubular lumen. Fragments of the
renal epithelium in the collecting ducts sloughs off and may be visible in the
microscopic examination of urine.

Ischemic ATN often develops following a hypotensive event leading to a

decrease in renal perfusion resulting to renal ischemia. Three principal causes of
ischemic acute tubular necrosis are sepsis (bacterial infection), shock (severe burns)

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
10
 and trauma (crush injuries). Any obstruction to renal blood flow such as
atherosclerosis results may also result to ischemic ATN.

Toxic Acute Tubular Necrosis

This type of tubular disease involves necrosis in the proximal convoluted

tubules but not including the basement membrane. Due to this, distinctive large
convoluted renal tubular epithelial cells from the PCT are found in the urine of the
patient. Patients may also manifest clinical features similar to ischemic ATN because
of some nephrotoxins causing renal vasoconstriction.

This is often caused by endogenous or exogenous nephrotoxic agents.

Endogenous agents are normal substances in circulation that become nephrotoxic in
higher concentration. Examples are hemoglobin (severe hemolytic episodes),
myoglobin (rhabdomyolysis), uric acid (Lesch-Nyhan disease) and immunoglobulin
light chains (multiple myeloma). On the other hand, exogenous agents are substances
ingested, injected, absorbed or inhaled and it includes therapeutic agents
(aminoglycosides), anesthetics (enflurane), radiographic contrast media,
chemotherapeutic drugs (cyclosporin), recreational drugs (heroin and cocaine),
industrial chemicals (heavy metals), organic solvents (carbon tetrachloride) and other
poisons.

Renal cast formation in the DCT and collecting ducts can be observed in both
types of ATN. However, an increased number and variety of casts (granular, renal
tubular cell, waxy and broad casts) are commonly associated with ischemic ATN.

Figure 1.13 Difference of two types of ATN

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
11
 TUBULAR DYSFUNCTION

Common tubular dysfunction includes Fanconi syndrome, cystinosis and cystinuria,

renal glucosuria, renal phosphaturia and renal tubular acidosis. Fanconi syndrome is
characterized by generalized loss of function of proximal convoluted tubules. This results to
amino acids, glucose, water, phosphates, potassium and calcium not being reabsorbed and
therefore excreted in urine.

Renal tubular acidosis (RTA) is an autosomal dominant disorder resulting to the

inability of the tubules to produce an acid urine despite adequate hydrogen ions for secretion
and a normal GFR. Four types of RTA have been identified based on their renal tubular
defect/s.

Type I is characterized by the inability to maintain the normal hydrogen ion gradient
and increases the secretion of ammonia to compensate.

Type II is characterized by the decreased reabsorption of bicarbonates in the PCT.

This results to the utilization of hydrogen ions to reabsorbed bicarbonates in
the DCT instead of being eliminated in urine.

Type III is a combination of type I and type II RTA defects.

Type IV is characterized by the impaired ability to exchange sodium for potassium and
hydrogen in the distal tubule.

Cystinosis is an autosomal recessive disorder resulting to cystinuria which is the

urinary excretion of the amino acid cystine (A detailed discussion of this will be in Module 6).

Renal glucosuria is a benign inherited condition that lowers the maximal tubular
reabsorptive capacity of the tubules resulting to glucosuria.

Renal phosphaturia or familial hypophosphatemia is a rare dominant sex-linked

disorder characterized by the inability of the DCT to reabsorb inorganic phosphorus. The
condition appears to be a two-fold defect wherein the DCT is hypersensitive to the parathyroid
hormone increasing phosphate excretion and a decrease PCT response to
hypophosphatemia. The decrease in plasma phosphate level, bone growth and mineralization
are decreased.

Table 1.2 Summary of typical Urinalysis results for selected tubular diseases.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
12
 TUBULOINTERSTITIAL DISEASE AND URINARY TRACT INFECTION

Due to the proximity and interconnectedness in function of the renal tubules and renal
interstitium, a disease in the renal tubules inevitably affects the renal interstitium, and vice
versa. Several conditions are capable of causing tubulointerstitial disease such as infections
(pyelonephritis or interstitial nephritis), toxins, metabolic diseases, vascular diseases,
neoplasms and multiple myeloma. Other than those mentioned, drugs, irradiation and
transplant rejection can also cause tubulointerstitial disease. Among these conditions, lower
urinary tract infection is closely related to tubulointerstitial disease as the former presents the
mechanism leading to the development of acute pyelonephritis.

Urinary tract infection (UTI) may involve either the lower or upper urinary tract. Lower
UTI may involve the urethra (urethritis), bladder (cystitis) or both. Whereas the upper UTI can
involve the renal pelvis (pyelitis) and/or interstitium (pyelonephritis).

Normally, urine along the urinary tract is sterile and the only the distal portion of the
urethra has normal flora. This normal flora remains isolated in the urethra due to continual
flushing during voiding. In spite of frequent urination, UTI is commonly caused by bacteria
from the GI tract. In other words, because of various factors, intestinal bacteria get introduced
into the urinary tract, where they proliferate and cause an infection.

Generally, UTI is more common among females than in males due to anatomy,
hormones, absence of prostatic fluid and “milking” of bacteria up the urethra during sexual
intercourse. Females have a shorter urethra with close proximity to the vagina and rectum.
Hormones enhance bacterial adherence to the mucosa of the urethra. Prostatic fluid, which
has antibacterial action, is not secreted by females.

The urinary tracts of men and women are susceptible to yeast infection, although such
infections occur more commonly in the vagina. Candida species (e.g., Candida albicans) are
normal flora in the gastrointestinal tract and vagina, and their proliferation is kept in check by
the normal bacterial flora in these areas. When the bacterial flora is adversely disrupted by
antibiotics or pH changes, yeasts proliferate and may cause an infection.

Common signs and symptoms of UTI include painful urination (dysuria), frequent urge
to urinate (urgency) and occasional low-grade fever and cramping. Among geriatric patients,
mental confusion or distress may occur.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
13
 ACUTE PYELONEPHRITIS

This involves the renal tubules, interstitium and renal pelvis as a result of an ascending
infection (movement of bacteria from the lower urinary tract to the kidneys) or hematogenous
infection (localization of bacteria from the bloodstream in the kidneys).

The most common cause is an ascending urinary tract infection from gram-negative
organisms that are normal intestinal flora. Usually if bacteria reach the bladder, they are
prevented from ascending the ureters to the kidneys by the continual flow of urine into the
bladder and by other antibacterial mechanisms.

The presence of bacteria in the interstitium results to acute inflammation and tubules
becoming necrotic. The presence of bacterial toxins and leukocytic enzymes results to the
formation of abscesses. The glomeruli are rarely involved and therefore has a normal
function.

Predisposing factors to acute pyelonephritis include conditions or procedures that

causes the proliferation and movement of bacteria to the upper urinary tract. One example is
the vesicoureteral reflux which refers to the abnormal movement of urine from the bladder to
the ureter as a result of an inherited congenital defect. Other conditions include
catheterization, urinary tract obstruction, sepsis, pregnancy, diabetes mellitus and
immunosuppression.

Patients with acute pyelonephritis experience acute pain in their flank, back or groin
and nocturia together with typical UTI clinical features (dysuria and urgency to urinate). In
some cases, high fever, chills, nausea, headache and generalized malaise may also be
experienced by the patient.

CHRONIC PYELONEPHRITIS

This type of infection often develops when there is persistent inflammation of the
renal tissue resulting to fibrosis and scarring of the renal calyces and renal pelvis. It is
commonly caused by reflux nephropathies such as vesicoureteral reflux, urinary tract
obstruction and intrarenal reflux. Intrarenal reflux is the movement of urine back to the
collecting duct and as far as the renal cortex due to a structural abnormality. Patients with
this condition experience hypertension, polyuria, nocturia and renal failure (in 10 – 15% of
cases).

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
14
 ACUTE INTERSTITIAL NEPHRITIS (AIN)

This is caused by an allergic response in the interstitium of the kidney, usually from an
acute allograft rejection after kidney transplant. Other than that, allergic reactions to
antibiotic, NSAIDs, antiepileptics and allopurinol can also cause AIN. These agents usually
induce cell-mediated immune response causes damage to the interstitium (edema and
infiltration) and tubules (necrosis) while the glomeruli and blood vessels are normal.

Clinical features associated with drug-induced AIN include fever, skin rash and
eosinophilia. With medications, these symptoms may resolve and renal function returns to
normal. However, irreversible damage may also occur, if untreated, especially among the
elders.

Table 1.3 Summary of typical Urinalysis results of Selected Tubulointerstitial diseases

VASCULAR DISEASE

As mentioned earlier, renal function depends on adequate renal perfusion. Therefore,

any condition that affecting perfusion can cause renal diseases. Atherosclerosis is a vascular
disease that reduce renal blood flow. On the contrary, hypertension, polyarteritis nodosa,
eclampsia, diabetes and amyloidosis causes structural changes on the arterioles and
glomerular capillaries resulting to ischemia.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
15
 ELABORATE– CONNECTING CONCEPTS
RENAL FAILURE

As mentioned earlier, some of these diseases may result to renal failure which can
have an acute or chronic onset.

ACUTE RENAL FAILURE (ARF)

This is characterized by a sudden loss of renal function with the nephron appearing
normal histologically. This type of renal failure is often reversible when prompt diagnosis and
treatment is given to the patient. However, it has a higher mortality rate due to concomitant
infection and potassium intoxication. ARF is caused by prerenal, renal and postrenal
mechanisms.

Prerenal mechanism causes 25% of ARF cases and is commonly caused by

decreased renal perfusion resulting to ischemia. These conditions include but not limited to
decreased cardiac output, hemorrhages, burns, surgical procedures, diarrhea and vomiting.
Other clinical findings include low urine sodium, higher urine osmolality than serum and an
increased BUN: Creatinine ratio.

Renal mechanism causes majority of ARF (65%) cases. This mechanism includes
glomerular, tubular and vascular diseases. As previously discussed, these renal diseases
cause damage and therefore affecting the function of the implicated structure.

Postrenal mechanism accounts for the remaining 10% of ARF cases and is commonly
associated with obstruction to urine flow. This obstruction causes an increase in hydrostatic
pressure in the tubules and bowman’s capsule resulting to damage.

CHRONIC RENAL FAILURE (CRF)

This type of renal failure is characterized by irreversible progressive loss of renal
function. The glomerular filtration rate slowly but continuously decreases and becomes only
clinical recognizable when 80-85% of normal renal function is lost (GFR=15-20 mL/min). The
“slow and silent” progression of CRF is partly due to the ability of the healthy nephrons to
compensate for damaged nephrons. By wear and tear principle, these healthy nephrons
become overworked and undergo hypertrophy until they lose their function as well.

Some conditions that cause CRF include glomerulonephritis, diabetic nephropathy,

chronic pyelonephritis, hypertension, systemic lupus erythematosus and congenital
abnormalities. Patients with CRF experience, azotemia, acid-base imbalance, water and
electrolyte imbalance and abnormal calcium and phosphate metabolism. Eventually these
findings, lead to end-stage renal disease. Typical urinalysis results of patient with CRF include
isosthenuria, proteinuria, hematuria and all types of casts.

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
16
 EVALUATE– ACTIVITY ALERT!
RENAL DISEASES AND RENAL FAILURE
This is a graded lecture activity worth 10 points.

I. Categorize the following renal diseases as to the type of syndrome they manifest.

A. Nephrotic Syndrome B. Nephritic Syndrome

1. Focal Glomerulosclerosis
2. IgA Nephropathy
3. Membranous Glomerulonephritis
4. Rapidly progressive glomerulonephritis
5. Poststreptococcal Glomerulonephritis

II. Characterize the following renal diseases by selecting all their morphological changes.

and sclerosis
Hyalinization
proliferation

membrane
Leukocytic
Infiltration

thickening
Basement
Cellular

6. Minimal Change Disease

7. Membranous Glomerulonephritis
8. Membranoproliferative Glomerulonephritis
9. Rapidly progressive glomerulonephritis
10. IgA nephropathy

Property of and for the exclusive use of SLU. Reproduction, storing in a retrieval system, distributing, uploading or posting online, or transmitting in
any form or by any means, electronic, mechanical, photocopying, recording, or otherwise of any part of this document, without the prior written
permission of SLU, is strictly prohibited.
17