1. What are the common congenital anomalies of the kidney? Describe each disease.

Babies typically are born with two kidneys. The kidneys filter waste in the blood, create
essential hormones the body needs to regulate blood pressure and help produce red blood
cells. Here are some of the most common kidney abnormalities in children:
● Horseshoe kidney: The kidneys may be fused together, forming a single arched kidney
● Polycystic or multicystic kidney disease: One or both kidneys have fluid-filled cysts
● Renal agenesis: Baby is born with one kidney, or baby is born without kidneys
● Renal hypoplasia: Baby is born with one or two abnormally small kidneys
● Renal dysplasia: One or both kidneys have not formed as they should.

2. What are the cystic diseases of the kidney? Describe each disease.
There are several types of CKD. Some are the result of mutations to certain genes that are
usually inherited (passed from parents to children). Others may develop during a person’s
lifetime, or they might be congenital (present at birth). Cysts can also appear in the kidney later
in life.
some genetic cystic kidney diseases
Genetic cystic kidney diseases include:
● Polycystic kidney disease: Autosomal dominant polycystic kidney disease is the most
common form of cystic kidney disease in adults. It’s usually diagnosed between the ages of
30 and 50. Another type of PKD is autosomal recessive polycystic kidney disease. It causes
abnormal kidney development in the womb or soon after birth. ARPKD is rare.
● Glomerulocystic kidney disease: GCKD causes cysts and enlargement of the space in the
kidneys near the urinary tract. It’s very uncommon but can affect infants or adults.
● Medullary cystic kidney disease: MCKD causes cysts to develop in the corticomedullary
(inner) part of the kidneys. It leads to inflammation and scarring of the tubes that help the
kidneys filter waste.
● Nephronophthisis: This condition is very similar to MCKD, but it affects infants, children and
teenagers. It usually leads to kidney failure before adulthood.

some non-genetic cystic kidney diseases

Non-genetic cystic kidney diseases include:
● Simple kidney cysts: These cysts are fairly common and usually affect older individuals. They
don’t tend to enlarge or disrupt the kidneys. In rare cases, cysts can be malignant and lead
to kidney cancer.
● Acquired cystic kidney disease: This disease causes cysts to develop over time due to
chronic kidney disease or kidney failure. It tends to affect adults or children who are on
dialysis.
● Multicystic dysplastic kidney: Kidney dysplasia is a common condition that occurs when one
or both kidneys don’t develop correctly in the womb. Cysts replace normal kidney tissue.
● Medullary sponge kidney: Cysts form on the innermost part of the kidneys. They block the
tubes that filter urine. It’s rare.

3. Compare nephritic syndrome from nephrotic syndrome. Tabulate your answer.

FEATURES NEPHROTIC SYNDROME NEPHRITIC SYNDROME

CHARACTERISTIC Edema - Hypo-albuminemia HTN-Mild Edema -

Proteinuria
Hypercholesterolemia (not Oliguria - Azotemia - High JVP
essential). - Dark Urine

MECHANISM Any Inflammation causes Immunological disorder

Proteinuria then
hypoalbuminemia and
hyperlipidemia.
Causing Thickening of BM
1. Anti-Basement Membrane
antibody.
2. Immune Complex (ppt of
BM).

GFR High (dt: High oncotic Low

pressure).

wqexz 1. Minimal change 1. Acute post

diseases. streptococcal
2. Membranous nephrititis
glomerulonephritis. Glomerulonephritis
3. Systemic vasculitis. 2. Glomerulonephritis in
4. Diabetic the course of collage
glomerulosclerosis. disorder as SLE.
5. Amyloidosis. May be rarely due to
6. Drugs-penicillamine 3. Viral infection;
Captopril- Gold - Hepatitis- Epstein Barr
Tetracycline. virus-
7. Sarcoidosis Cytomegalovirus
8. Right sided heart 4. Parasitic infection of
failure glomerulus;
9. Constrictive Plasmodium
Pericarditis falciparum.
5. Rapidly progressive
GN

EDEMA It is the only clinical sign
Massive edema, due to:
1. Increase in the
hydrostatic P. is more
than inc. in oncotic P.
at venular end.
2. Decrease in Oncotic P,
at venular end.
Causing lack of fluid
return to circulation
caused by Hypo-
proteinemia leading
to:
● Hypo- Valemia
● Aldosterone
Secretion
●
BP Normal due to; Hypovolemia
if increased may be due to
underlying HTN or DM or
Polyarthritis nodosa
CONGESTED NECK VEINS Empty Veins and Normal JVP
AND JVP due to: Hypovolemia Only is
high if the syndrome is cause
by Right- sided HF or
pericardial effusion
OTHER Hypercholesterolemia and
Lipid- urea
6. Acute tubule-
intestinal
7. Nephropathy.
Mild edema, due to:
1. Salt and water
Retention
2. Generalized Vasculitis
3. Heart failure
development
Hypertension ( acute rise in
youth) dt:
1. Hypervolemia (dt low
GFR)
2. Increase in Ren in
Secretion
May complicate to; LSHF- RF-
Retinalcomplic. -
Hypertensive Ecnephalopathy
High due to: Hypervolemia
With Congested Neck veins
as a characteristic sign
Fever- Bilateral; Loin Pain
( Edema stretches renal
capsule causing pain)
 SERUM ALBUMIN Low Normal or Slightly reduced

RED BLOOD CELLS Absent Present

PROTEINURIA ++++ ++

HEMATURIA May or May not occur +++

4. What are the three methods of microscopy applicable to renal biopsy glomerular diseases?
Describe each method.
Methods of microscopy applicable to renal biopsy glomerular diseases:
Light microscopy:
Tissue for LM is processed, dehydrated, and placed in paraffin block, and multiple serial sections
are obtained and stained. Usual stains include hematoxylin & eosin, periodic acid-Schiff silver
methenamine (Jones’), and Masson trichrome. Additional unstained slides are produced to
allow additional special studies as needed. Five hours of processing, sectioning, and staining
time are typically needed to produce LM slides.
Immunofluorescence microscopy :
Tissue for IF is surrounded with OCT compound and frozen, and sections are produced and
stained with fluorescein-tagged antibodies against IgG, IgA, IgM, complements C3 and C1q, κ
and λ light chain. Complement product C4d may also be stained on frozen tissue, with more
technical difficulty in staining on paraffin-block tissue. One to 2 hours of processing, sectioning,
and staining time are needed for production of IF slides.
Electron microscopy:
EM tissue is processed and embedded in a plastic, hard media, and scout sections (so-called
thick sections) are stained with toluidine blue to identify the specific area to be cut for thin
sections to be placed on a grid for EM examination. Typically 2 working days are needed to
process and produce EM sections for ultrastructural examination.

5. What are the primary glomerulopathies (nephritic type)? Describe the etiology,
pathogenesis, morphologic characteristics and clinical manifestations.
The nephritic syndrome is a common presentation of most proliferative glomerulonephritides.
The nephritic syndrome can be due to acute proliferative glomerulonephritis (postinfectious
and infection associated), crescentic glomerulonephritis, and proliferative lupus
glomerulonephritis.

Etiology:
In children, the most common cause of acute glomerulonephritis is post-streptococcal
glomerulonephritis. Sudden onset of the nephritic syndrome occurs seven to ten days after a
streptococcal throat or 2-3 weeks after a skin infection (impetigo). The most common pathogen
involved is group A-beta hemolytic streptococci. Only a few strains of the bacteria are
nephritogenic. Over 90% of the patients show a previous infection with types 12, 4, and 1
Streptococci. These are identified by typing of the M protein of the bacterial cell walls. A similar
form of glomerulonephritis (infection associated) may occur in association with certain
infections, e.g., bacterial infections (meningococcemia, staphylococcal endocarditis, and
pneumococcal pneumonia, etc.), viral infections (mainly hepatitis B, hepatitis C, mumps, HIV
infection, varicella, and EBV causing infectious mononucleosis), and parasitic infections (malaria
and toxoplasmosis).
Crescentic or rapidly progressive glomerulonephritis (RPGN) is characterized by the nephritic
syndrome presenting with the clinical picture of sudden and severe acute renal failure.
However, RPGN does not have a specific etiology. It may occur due to:
Anti-GBM antibody-mediated disease (e.g., Goodpasture syndrome)
Diseases caused by immune complex deposition, with granular deposits of antibodies and
complement by immunofluorescence: This results from the complication of any of the immune
complex nephritides and includes postinfectious glomerulonephritis, lupus nephritis, IgA
nephropathy, and Henoch-Schönlein purpura.
Pauci-immune crescentic GN may be associated with systemic or renal vasculitis.
In systemic lupus erythematosus (SLE), patients with focal or generalized proliferative
glomerular inflammation can present with nephritic syndrome.

morphologic characteristics:
Poststreptococcal Glomerulonephritis: Light microscopy picture shows that the glomeruli are
diffusely enlarged with endocapillary proliferation and neutrophil infiltration. The
immunofluorescence microscopy shows a "starry sky pattern" due to subepithelial "lumpy"
granular deposition of IgG and C3. Electron microscopy will demonstrate the "lumpy"
subepithelial immune deposits. Mesangial deposits may also be seen in some patients.

Staphylococcal Glomerulonephritis: The majority of patients have focal endocapillary

glomerulonephritis with peripheral capillary occlusion due to endothelial cell proliferation and
neutrophil infiltration. Capillary tufts may show necrosis. "Lumpy" subepithelial immune
deposits are seen. In some patients, mesangial proliferative glomerulonephritis (also called
membranoproliferative glomerulonephritis or MPGN) may be seen with marked mesangial
proliferation and granular immune deposits within the basement membrane.
Crescentic Glomerulonephritis: The crescent is formed by the proliferation of epithelial cells in
the parietal layer of the Bowman capsule. Macrophages, fibrin exudates, fibroblasts,
complement products may be seen trapped in the mesangium and the Bowman's capsule
space. In addition to this, other features of disorder-specific lesions may be seen in different
diseases. In Goodpasture syndrome, there is a linear deposition of IgG antibodies and C3 along
the GBM. Lupus nephritis has a "full-house pattern" with IgG, IgM, IgA, C3 immune deposits
present diffusely in the mesangium, sub epithelium, and sub-endothelium. Anti-GBM antibodies
or immune complexes are not detected by immunofluorescence and electron microscopy in
pauci-immune crescentic glomerulonephritis. Vasculitis may be seen on renal biopsy.

6. What are the primary glomerulopathies (nephrotic type)? Describe the etiology,
pathogenesis, morphologic characteristics and clinical manifestations.
primary glomerulopathies (glomerulonephritides) : Affects the kidney directly.

Etiology:

It may also be caused by other illnesses, including lupus, Goodpasture's syndrome, Wegener's
disease, and polyarteritis nodosa. Early diagnosis and prompt treatment are important to
prevent kidney failure.

morphologic characteristics:

Pink or cola-colored urine from red blood cells in your urine (hematuria) Foamy or bubbly urine
due to excess protein in the urine (proteinuria) High blood pressure (hypertension).

Clinical manifestations:

Nausea and vomiting, muscle cramps, loss of appetite, swelling via feet and ankles, dry, itchy
skin, shortness of breath, trouble sleeping, urinating either too much or too little.

7. What are the common causes of secondary glomerulopathies? Describe each one.
secondary glomerulopathies effects indirectly causes includes diabetes, lupus, infection, or drug
use
Diabetes: Anyone with diabetes can develop nephropathy. High glucose levels are thought to
make the blood flow into the kidney at a higher speed, putting a strain on the filtering process
and raising blood pressure. The capillaries in the glomerulus collapse and can leave the
glomeruli with scarring. People with diabetes should control their glucose intake by eating a
balanced, nutritious diet, and keep their blood pressure below 140 over 90 millimeters of
mercury (mmHg), for example, by using medications, such as ACE inhibitors. This can help
prevent kidney complications, such as glomerulonephritis.

Lupus or infection: Conditions including lupus and infection may cause scarring of the
glomeruli, also known as glomerulosclerosis, Scarring occurs when growth factors activate the
glomerular cells to produce scar material. The growth factors may be produced by the
glomerular cells or carried by circulating blood. This can lead to protein in the urine and
eventual kidney failure.

8. Describe the renal lesions found in systemic lupus erythematosus.

Renal microvascular lesions, common in lupus nephritis , are associated with long-term poor
outcomes. There are mainly five pathological types of renal microvascular lesions in LN:
(1) vascular immune complex deposits
(2) arteriosclerosis
(3) thrombotic microangiopathy
(4) non-inflammatory necrotizing vasculopathy
(5) true renal vasculitis
The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation
and dysfunction of endothelial cells, in addition to the contribution of immune system
dysfunction, especially the immune complex-induced vascular inflammation and
antiphospholipid antibody-associated thrombotic events, are key mechanisms in the
development of vascular lesions in LN that need to be further investigated. Alteration of the
microvascular environment produces an acute immunological response that recruits immune
cells, such as T cells, monocytes, and macrophages, which induces platelet aggregation with
micro thrombus formation. There is also increased cytotoxicity caused by cytokines produced by
immune cells in the kidney. Identifying the mechanism underlying the pathogenesis of renal
microvascular lesions in LN might provide potential targets for the development of novel
therapies.
The pathogenesis of renal microvascular lesions in LN is not fully understood. Results from
animal models and human lupus experiments have suggested that the activation and
dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction,
especially the immune complex-induced vascular inflammation and antiphospholipid
antibody-associated thrombotic events, are key mechanisms in the development of renal
microvascular lesions in LN that need to be further investigated [6]. Although different types of
vascular lesions share certain common mechanisms, each morphological lesion type may exhibit
its own unique factors that result in a morphological presentation that differs from other types
of lesions.
9. Describe the entity chronic glomerulonephritis.
Chronic glomerulonephritis is characterized pathologically by varying degrees of glomerular
scarring that is always accompanied by cortical tubular atrophy, interstitial fibrosis, interstitial
infiltration by chronic inflammatory cells, and arteriosclerosis. Chronic glomerulonephritis is the
most frequent cause of CRF. Chronic glomerulonephritis does not always cause CRF. In one
study 40% of equine kidneys examined at necropsy had microscopic glomerular lesions); there
are two types of lesions:

● Anti Glomerular basement membrane glomerulonephritis – (anti-GBMG) – is due to

antibodies directed against the glomerular basement membrane.

● Immune complex glomerulonephritis (ICG) – (the most common type) – is due to

deposition of immune complexes along the glomerular basement membrane. Immune
complexes may be associated with upper respiratory infections caused by Streptococcus
spp. With either type, the glomeruli become inflamed and the glomerular membrane
becomes thickened by fibroblasts.

10. What are the common diseases of the renal tubules and interstitium? Describe the
etiology, pathogenesis, morphologic characteristics and clinical manifestations.
common diseases of renal tubules and interstitium:
● Analgesic Nephropathy
● Contrast Nephropathy

Analgesic nephropathy:
Etiology: Analgesic nephropathy involves damage within the internal structures of the kidney. It
is caused by long-term use of analgesics especially over-the-counter (OTC) medicines that
contain phenacetin or acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs), such
as aspirin or ibuprofen.

Pathogenesis: Analgesic nephropathy is a well-described cause of CKD characterized by renal

papillary necrosis and chronic interstitial nephritis. It results from prolonged and excessive
consumption of analgesic mixtures containing potentially addictive substances in addition to
analgesics

Morphologic characteristics: Conventional histologic and electron microscopic studies

confirmed a medullary site for the earliest lesion, which appeared to be an increase in
interstitial collagen. Other early abnormalities included focal thickening of tubular basement
membranes, degeneration, atrophy or loss of tubular epithelium, and casts. These
abnormalities were apparent when renal function was not demonstrably reduced. They
progressed to become a diffuse sclerosis or necrosis of the medulla, and only then were cortical
histologic abnormalities present. These included peritubular, interstitial and periglomerular
fibrosis; tubular atrophy, dilatation and basement membrane thickening; and in some focal
round cell infiltration

Clinical manifestations: Fatigue or weakness, feeling unwell, Blood in the urine, An increase in
urination frequency or urgency, Pain in the back or flank area,
A decrease in urine output, Decreased alertness, such as drowsiness, confusion, or lethargy.

Contrast nephropathy:
Etiology: Contrast-induced nephrotoxicity (CIN) is a form of acute kidney injury that follows
intravascular contrast media exposure. CIN may be preventable because its risk factors are well
established and the timing of renal insult is commonly known in advance.

Pathogenesis: The pathogenesis of CIN is complex and not fully understood, but iodinated
contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction
of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the
kidney through a loss of nitric oxide production.

Morphologic characteristics:
Contrast-induced nephropathy (CIN) is defined as the impairment of kidney function measured
as either a 25% increase in serum creatinine (SCr) from baseline or a 0.5 mg/dL (44 µmol/L)
increase in absolute SCr valuewithin 48-72 hours after intravenous contrast administration

Clinical manifestations:
CIN is associated with a sharp decrease in kidney function over a period of 48-72 hours. The
symptoms can be similar to those of kidney disease, which include feeling more tired, poor
appetite, swelling in the feet and ankles, puffiness around the eyes, or dry and itchy skin

11. Describe the entity urolithiasis. What are the common compositions of the stones?
Urosepsis, renal abscess, infected stones, chronic kidney disease (CKD), obstruction, ureteral
scarring, and stenosis are all complications of ureterolithiasis.
Possible causes include drinking too little water, exercise (too much or too little), obesity, weight
loss surgery, or eating food with too much salt or sugar. Infections and family history might be
important to some people.
Common compositions of the stones, Calcium stones: Most kidney stones are composed of
calcium and oxalate.
Struvite stones: Some patients form stones that are composed of a mixture of magnesium,
ammonium, phosphate and calcium carbonate, which is known as struvite.
Uric acid stones: Uric acid is produced when the body metabolizes protein.

12. What are the benign tumors of the kidneys? Describe the etiology, pathogenesis,
morphologic characteristics and clinical manifestations.
Renal adenoma – Most common form, solid kidney tumor, and are typically small, low-grade
growths. Their cause is unknown.
Renal oncocytoma –usually an asymptomatic tumor that can grow quite large. They can develop
throughout the body and are not unique to the kidneys. Their cause is also unknown, and they
appear with greater frequency in men than in women.
Angiomyolipoma – Also known as renal hamartoma, are rare, benign tumors that can be caused
by an inherited genetic mutation. They can occur on an isolated, individual basis, but most often
are associated with a rare genetic disease called tuberous sclerosis, which can cause tumors in
the skin, kidneys, brain and other organ systems. In patients without tuberous sclerosis, these
tumors most often occur in middle-aged women.
Fibroma – Fibromas are tumors of the fibrous tissue on, in or surrounding the kidney. They are
rare and more common in women. Their cause is unknown and most do not cause symptoms.
Lipoma – Lipomas are rare renal tumors originating in the fat cells within the renal capsule or
surrounding tissue. Lipomas typically occur in middle-aged women.
Etiology:
Smoking
Obesity, poor diet
High blood pressure
Being on kidney dialysis
Workplace exposure to chlorinated chemicals
Heredity

Symptoms may include:

• Blood in the urine
• Pain or a lump in the lower back
• Fatigue
• Loss of appetite
• Unexpected weight loss
• Fever
• Anemia

13. What is renal cell carcinoma? Describe the etiology, histological variants and their genetic
abnormalities.
In the context of the natural history of the disease, it is important to consider that at some point
during their development all tumors are small. Renal tumors under a certain size have,
historically, been referred to as renal adenomas particularly when discovered incidentally. The
finding of small renal tumors in adult autopsy series suggested that the incidence of smaller RCC
is much more common than “overtly malignant RCC”. The definition of adenoma has changed
over time and between cell types. For papillary RCC, lesions under 2.5–3cm were previously
termed adenoma but now adenoma is defined as 0.5cm or smaller. An adenoma to carcinoma
sequence has been described in papillary RCC. Renal adenoma cannot be distinguished from
carcinoma by morphological criteria. The distinction between adenoma and carcinoma appears
somewhat arbitrary based on size and outcome and has been, and likely, will continue to be
redefined. At least on a molecular genetic basis, it would seem that the precursor of a RCC is a
smaller RCC sometimes called adenoma.

Premalignant precursor lesions of RCC are not well-characterized. The best described putative
precursor lesions are the simple cyst to atypical cyst to clear cell RCC common in inherited VHL
patients. Intratubular epithelial dysplasia defined by morphological criteria of nuclear crowding
and nuclear enlargement has been reported by several groups in around a quarter of RCC
patients. The dysplasia can be subdivided by the severity of the lesion from mild dysplasia to
high grade renal intratubular neoplasia (RIN). However, such dysplasia remains understudied
and outside the current recommendations for the pathological reporting of RCC.

Multifocal RCC
Approximately 10–15% of sporadic RCC are multifocal in the same kidney at presentation.
Papillary RCC is more frequently multifocal than clear cells. Importantly, in many cases there is
an obvious difference in size between the multiple RCC. Most commonly, there is an obvious
renal carcinoma and a much smaller lesion(s) often termed satellite lesions. This designation
implies that the small lesions have arisen by intra-renal spread from the main (by size) tumor.

Two studies of a comparison of molecular genetic alterations of multifocal clear cell RCC had
similar findings that suggested a common clonal origin in the majority. In contrast, another
study found evidence for a polyclonal origin in around half of the multifocal RCC patients
studied . A study of multifocal papillary RCC found different alterations in each lesion from the
same patient for an opposite conclusion for this cell type. In addition, the accuracy of the
microsatellite allelotyping in one of the studies has been challenged, the robustness of the
X-chromosome inactivation clonality assay, in general, has been questioned , and that an
identical pattern of X-chromosome inactivation or LOH can plausibly arise by chance.

As well as insight into the natural history of RCC, multifocal RCC have been studied with regard
to the implications of the presence of small lesions in the kidney remnant after nephron sparing
surgery. Initial observations described a lower level of recurrence after partial nephrectomy
(1%) compared to the incidence of multifocal disease (10–15%) and implied a lesser malignancy
of satellite lesions. While it may be too early in the adoption of nephron sparing surgery for any
increase in recurrence rate to be apparent, for T1 RCC survival after partial nephrectomy
appears statistically indistinguishable from radical nephrectomy.

Overall, the typically smaller size of the satellite lesion(s), the physical proximity to the main
tumor, the similar histopathology, and the albeit understudied similar (in clear cell) molecular
alterations, all argue for the smaller lesion(s) having arisen from intra-renal spread from the
main tumor. However, as discussed above, the molecular evidence remains equivocal and it is
difficult to reconcile the satellite lesions having the same alterations present in the main tumor
and intra-renal metastasis with the partial nephrectomy survival data. There are RCC patients
with two or more tumors of several cm in size in the same kidney as well as patients with
bilateral RCC. RCC patients younger than 40 years are at greatly increased risk of RCC in the
other kidney. Some of the bilateral RCC patients may be unidentified familial RCC.RCC in End
Stage Renal Disease Patients
In addition to individuals with inherited syndromes that strongly predispose to RCC, there is a
second, rapidly increasing, group at high risk. These are individuals on long-term dialysis
particularly those with acquired cystic kidney disease (ACKD). More than 100,000 people in the
US will begin treatment for end stage renal disease. ACKD is characterized by the development
of numerous fluid-filled cysts in the kidneys in individuals who have no history of hereditary
cystic disease. The definition is somewhat arbitrary as the threshold of cystic changes has not
been agreed upon. Thus the prevalence of ACKD in patients with end stage renal failure varies
between 30% and 90% according to the definition of ACKD, time on dialysis and type of
investigation performed . The exact cause of this disease is not known. It occurs exclusively in
patients on dialysis. The severity of disease is directly related to the duration of therapy. ACKD
occurs in about 20% of patients with end stage renal disease prior to dialysis, this increases to
60–80% in patients with 4 years of dialysis, and to 90% in patients with 8 years or more of
dialysis . Typically, ACKD is asymptomatic in patients with acquired cystic disease who are more
likely to develop RCC at an estimated 40-fold higher incidence. Renal cell carcinoma occurs
approximately 20 years earlier in people with acquired renal cystic disease than in the general
population. ACKD is more frequent in men and African-Americans are significantly more likely
both to both be on dialysis and to have ACKD. ACKD patients have more bilateral, multifocal,
and papillary RCC than the general population . The benefit of early detection of RCC in ESRD
would be that the RCC would be less likely metastatic and hence ultimately fatal. ESRD patients
are not routinely scanned for RCC unless there are other issues. Transplantation also carries an
increased risk for kidney cancer this is estimated to be 15-fold over the first three years
following transplantation, and this risk increases with the extent of exposure to
immunosuppressive agents. The prevalence of RCC in native kidneys after transplantation is
around 5% overall but 19% in CKD patients or 54% in patients with complex cysts. The life
expectancy of a transplant recipient has improved and cancer may soon be the leading cause of
death late after transplantation. A marker of aggressiveness of RCC developing after
transplantation could also aid in establishing priority for transplantation.

Risk, Prevention, and Early Detection of RCC

Individuals with inherited syndromes that predispose to RCC and long-term dialysis patients are
at high risk but account for a minority of RCC cases. Algorithms of relative risk of RCC according
to smoking status, body mass index and blood pressure have been investigated and a decrease
in risk was observed for men who had stopped smoking for 30 years or more. The only evidence
for the potential of chemoprevention for RCC are studies which show diets rich in fruit and
vegetables as well as high vitamin D levels to be preventive. Candidates for a future
chemopreventive strategy would be inherited RCC, ESRD patients and also RCC patients at high
risk of recurrence.
In regard to early detection, despite increasing incidental detection, the problem remains of the
RCCs that are locally advanced or metastatic upon diagnosis. Unless risk factors are uncovered,
the death rate from advanced RCCs at presentation may only be reduced by a screening test for
RCC in the general population that could detect such RCC at an earlier and curative stage. Renal
cancer is “neither a common nor a rare disease”. However, the relative incidence of RCC and
considerations of cost effectiveness virtually dictate that a screening test of the general
population for RCC must be “bundled” with simultaneous screening for a, or more likely several,
more common types of solid tumors; however, a screening test in non-invasive body fluids,
urine or blood, will require a method of differential diagnosis of the organ site of cancer from
which the positive test originated.
Molecular early detection strategies must be designed with careful regard to the abundance of
tumor cells in the clinical specimen as well as the frequency and timing of the alteration to be
detected. LOH of 3p and point mutation of VHL are frequent and early in clear cell RCC but urine
or blood contain a low ratio of DNA from renal tumor cells to DNA from normal cells that is
insufficient for the robust detection of these alterations by polymorphic marker and sequencing
analysis respectively. Because point mutations occur throughout the VHL gene, rather than at
hotspots of particular codons like RAS, the design of more sensitive oligonucleotide molecular
tests is very complicated. However, if a tumor cell-rich biopsy specimen is available, LOH and
point mutation can be assessed as prognostic markers. Because aberrant hypermethylation of
particular tumor suppressor and other cancer genes can be common, early and cancer specific
as well as amenable to detection by the sensitive MSP technique which is capable of detecting
one methylated allele from a neoplastic cell in a background of several thousand unmethylated
alleles from normal cells, a number of feasibility studies of methylation-based detection of
cancer in body fluids have been performed. We have demonstrated the feasibility of
methylation-based detection of kidney cancer. Our initial study selected a panel of 6 genes (the
tumor suppressor genes VHL, p16, p14ARF and APC and the putative suppressor genes RASSF1A
and Timp-3) the promoter regions of which are generally unmethylated in normal renal tissue.
Using methylation specific PCR (MSP), a pattern of gene hypermethylation identical to that
found in the RCC tissue sample was detected in matched DNA extracted from pre-operative
urine samples in 44 of 50 (88%) patients. Gene methylation was positively detected in urine
samples from patients with organ-confined (stage I and II) RCC, including tumors as small as 2.2
cm in size. In contrast, methylation of all 6 genes used in the panel was absent in normal renal
tissue and urine from a small number of normal and non-neoplastic disease controls. We have
demonstrated the feasibility of sensitive and specific detection of genes aberrantly methylated
in RCC in pre-operative urine DNA. Other investigators confirmed these findings in a subsequent
qMSP study of gene methylation in urine DNA from patients with RCC. Urakami et al reported
conventional MSP-based detection of methylation of SFRP1 and other Wnt-antagonist genes in
33% of serum of RCC patients and 0% in serum from normal age-matched controls. This
approach requires validation in larger, well-defined populations with optimized and
standardized methodology. Further insight into the timing of gene methylation during aging and
the earliest stages of neoplastic development will be necessary. Depending upon the population
and the specimen to be screened, differential diagnosis will be of a greater or lesser degree of
importance.

14. What is meant by chronic renal failure? Describe the presentation.

Chronic renal failure is a condition involving a decrease in the kidneys' ability to filter waste and
fluid from the blood. It is a condition that develops over a long period of time and is not
reversible. The condition is also commonly known as chronic kidney disease.
People with diabetes and hypertension, who are at high risk of developing chronic renal failure.
Symptoms:
The urge to urinate more frequently
Urine may be pale and foamy
Hypertension
Swelling of the legs
Poor appetite
Weight loss.
There are two diagnostic tests for CRF:
Glomerular filtration rate: To check the filtration rate, a blood sample and the results are
combined with age, gender, height, weight to estimate the filtration rate.
Creatinine clearance test: Calculates the glomerular filtration rate. To perform the test, a person
needs to collect all their urine for a 24 hour period and then provide a blood sample. Comparing
creatinine levels in the blood and urine allows a person’s glomerular filtration rate to be
estimated.
Treatment:
Hemodialysis
Kidney transplantation

15. What are the vascular disorders of the kidneys? Describe the etiology, pathogenesis,
morphologic characteristics and clinical manifestations.
Renal artery stenosis (RAS): This is a narrowing or blockage of an artery to the kidneys. It may
cause kidney failure and high blood pressure. Smokers have a greater risk of getting RAS. It’s
most common in men between the ages of 50 and 70. High cholesterol, diabetes, being
overweight, and having a family history of heart disease are also risk factors for RAS. High blood
pressure is both a cause and a result of RAS.

Renal artery thrombosis: This is a blood clot in an artery that supplies the kidney. It may block
blood flow and cause kidney failure.
Renal vein thrombosis: This is the formation of a clot in a vein to the kidney.
Renal artery aneurysm: This is a bulging, weak area in the wall of an artery to the kidney. Most
are small and don’t cause symptoms. Renal artery aneurysms are rare and are often found
during tests for other conditions.
Atheroembolic renal disease: This happens when a piece of plaque from a larger artery breaks
off and travels through the blood. This blocks small renal arteries. This disease is becoming a
common cause of kidney problems in older adults.

Causes are:
Atherosclerosis
Injury
Infection
Inflammatory or other underlying disease
Surgery
Tumor
Aneurysm
Pregnancy
Certain medicines
Birth defect

Renal Artery Stenosis

• High blood pressure that doesn’t get better with 3 or more medicines.
• Increased urea (a waste product made by the kidneys) in the blood.
• Unexplained kidney failure.
• Sudden kidney failure when first taking an angiotensin-converting enzyme (ACE)
inhibitor for blood pressure and/or heart treatment
Renal Artery Thrombosis
• Sudden onset of side pain between the ribs and the upper border of the hip bone (flank
pain), pain and tenderness
• Fever
• Blood in the urine
• Nausea and vomiting
• Sudden decrease in kidney function
• High blood pressure
A gradual or incomplete clot may not cause symptoms and go undetected
Renal Artery Aneurysm
• There are often no symptoms·
• High blood pressure
• Tear in aneurysms may cause flank pain and blood in the urine
Atheroembolic Renal Disease
• Skin lesions or red or purple color of the skin.
• Discolored areas of the toes and feet
• Kidney failure
• Belly pain
• Diarrhea
• Confusion
• Weight loss
• Fever
• Muscle aches
Renal Vein Thrombosis
Slow Onset
• Most often causes no symptoms
Sudden Onset
• On-going severe flank pain with spasms at times
• Soreness over the kidney, between the ribs and the backbone
• Decreased kidney function
• Blood in urine

16. Explain the pathogenesis of hydronephrosis. Describe histologic and clinical presentation.
Hydronephrosis can result from anatomic or functional processes interrupting flow of urine This
interruption can occur anywhere along the urinary tract from kidneys to urethral meatus. Rise in
ureteral pressure leads to marked changes in glomerular filtration, tubular function & renal
blood flow. Glomerular filtration rate (GFR) declines significantly within hours following acute
obstruction. This significant decline of GFR can persist for weeks after relief of obstruction.
Symptoms:
Pain in the side and back that may travel to the lower abdomen or groin
Urinary problems, such as pain with urination or feeling an urgent or frequent need to urinate
Nausea and vomiting
Fever